|
1
|
Zengin M, Işıkçı ÖT. Tumour Budding Is a Useful Predictor to Identify High-Risk Stage II Colon Cancer Patients After Curative Surgery. Int J Surg Pathol 2025; 33:363-374. [PMID: 39094576 DOI: 10.1177/10668969241265017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Aim. Although it is now accepted in the literature that tumour budding (TB) is a useful survival indicator in colon cancer (CC), there are still uncertainties about daily use. Here we methodologically examined the role of TB on survival in CC. Methods. In our study, we examined colon cancer patients who had surgery up to 15 years before presentation. TB was calculated separately using different comprehensive methodological methods. Results. We first investigated an optimal evaluation method. Relationship with prognostic factors was better (Venous invasion [p = .001], advanced pT [p = .003], perineural invasion [p = .040], MSS [p = .016], advanced size [p = .001], tumour obstruction [p = .005], margin involvement [p = .043], and nodal involvement [p = .028]) in Method-1. Similarly, with the same method, the success of the cut-off value, the correlation of TB data (r = .724), and the repeatability of the method (Κappa = .53-.75) were quite good (ROC = .816 [.707-.925]). Then, survival analysis was performed using the best three methods, including this method. In univariate analysis using Method-1, survival analyses were worse in high TB patients (RFS: 81%, p < .001; OS: 84%, p < .001). Multivariate analyses using the same method confirmed that high TB for RFS and OS was an independent poor prognostic parameter for survival (p = .002, Hazard ratio [HR]: 1.42 [1.13-1.80]) and OS (p = .014, HR: 1.38 [1.07-1.79]). Conclusions. With our study, we showed that tumour budding calculated by the standard method is a very valuable prognostic parameter in stage II CC and can contribute to the detection of patients with poor prognosis in stage II CC.
Collapse
Affiliation(s)
- Mehmet Zengin
- Department of Pathology, Kırıkkale University, Kırıkkale, Turkey
| | - Özlem Tanas Işıkçı
- Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey
| |
Collapse
|
|
2
|
Maruyama S, Imamura Y, Toihata T, Haraguchi I, Takamatsu M, Yamashita M, Nakashima Y, Oki E, Taguchi K, Yamamoto M, Mine S, Okamura A, Kanamori J, Nunobe S, Sano T, Kitano S, Noda T, Watanabe M. FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. Cancer Sci 2025; 116:178-191. [PMID: 39440906 PMCID: PMC11711055 DOI: 10.1111/cas.16373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/21/2024] [Accepted: 10/03/2024] [Indexed: 10/25/2024] Open
Abstract
The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.
Collapse
Affiliation(s)
- Suguru Maruyama
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tasuku Toihata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ikumi Haraguchi
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Takamatsu
- Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makiko Yamashita
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Taguchi
- Department of Pathology, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Manabu Yamamoto
- Department of Gastroenterological Surgery, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Shinji Mine
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, Tokyo, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shigehisa Kitano
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tetsuo Noda
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
3
|
Imamura T, Komatsu S, Nishibeppu K, Kiuchi J, Ohashi T, Konishi H, Shiozaki A, Yamamoto Y, Moriumura R, Ikoma H, Ochiai T, Otsuji E. Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma. BMC Cancer 2024; 24:907. [PMID: 39069624 DOI: 10.1186/s12885-024-12676-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 07/23/2024] [Indexed: 07/30/2024] Open
Abstract
BACKGROUND This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach. METHODS We used the Toray® 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers. RESULTS (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P < 0.001, area under the receiver operating characteristic curve = 0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P = 0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P = 0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (ρ = 0.64, P = 0.005) between miR-210-3p expression in plasma and urine. CONCLUSIONS Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC. TRIAL REGISTRATION Not applicable.
Collapse
MESH Headings
- Humans
- MicroRNAs/urine
- MicroRNAs/blood
- MicroRNAs/genetics
- Female
- Male
- Biomarkers, Tumor/urine
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/blood
- Pancreatic Neoplasms/urine
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/blood
- Middle Aged
- Aged
- Adenocarcinoma, Mucinous/urine
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/diagnosis
- ROC Curve
- Case-Control Studies
- Gene Expression Regulation, Neoplastic
- Adult
- Carcinoma, Pancreatic Ductal/urine
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/blood
Collapse
Affiliation(s)
- Taisuke Imamura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Ryo Moriumura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshiya Ochiai
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| |
Collapse
|
|
4
|
Dai J, He B, Zhang Y, Zhang H, Hu X, Xu L, Ni Y, Zhang X, Sun G, Zeng H, Shen P, Liu Z. The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study. World J Urol 2024; 42:259. [PMID: 38662226 PMCID: PMC11045608 DOI: 10.1007/s00345-024-04973-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 04/02/2024] [Indexed: 04/26/2024] Open
Abstract
PURPOSE The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.
Collapse
Affiliation(s)
- Jindong Dai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ben He
- Department of Urology, The Third People's Hospital of Chengdu/The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610014, Sichuan, China
| | - Yaowen Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Haoran Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xu Hu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lijing Xu
- Department of Urology, Institute of Urology, West China Xiamen Hospital, Sichuan University, Xiamen, 361000, China
| | - Yuchao Ni
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xingming Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Guangxi Sun
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Pengfei Shen
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Zhenhua Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| |
Collapse
|
|
5
|
Støyten M, Knutsen T, Stikbakke E, Agledahl I, Wilsgaard T, Eggen AE, Richardsen E, Giovannucci E, Thune I, Haugnes HS. Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study. Acta Oncol 2024; 63:154-163. [PMID: 38591351 PMCID: PMC11332472 DOI: 10.2340/1651-226x.2024.32953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 02/16/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results. METHODS In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994-2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality. RESULTS At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39-6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30-0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03-2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11-3.70). INTERPRETATION In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.
Collapse
Affiliation(s)
- Martin Støyten
- Institute of Clinical Medicine, UIT - The Arctic University, Tromsø, Norway
| | - Tore Knutsen
- Department of Urology, University Hospital of North Norway, Tromsø, Norway
| | - Einar Stikbakke
- Institute of Clinical Medicine, UIT - The Arctic University, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Ingvild Agledahl
- Department of Urology, University Hospital of North Norway, Tromsø, Norway
| | - Tom Wilsgaard
- Institute of Community Medicine, UIT-The Arctic University, Tromsø, Norway
| | - Anne Elise Eggen
- Institute of Community Medicine, UIT-The Arctic University, Tromsø, Norway
| | - Elin Richardsen
- Department of Pathology, University Hospital of North Norway, Tromsø, Norway; Department of Medical Biology, UIT - The Arctic University, Tromsø, Norway
| | - Edward Giovannucci
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Inger Thune
- Institute of Clinical Medicine, UIT - The Arctic University, Tromsø, Norway; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Oslo University Hospital, Norway
| | - Hege S Haugnes
- Institute of Clinical Medicine, UIT - The Arctic University, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
| |
Collapse
|
|
6
|
Gallagher BDT, Chiam K, Bang A, Patel MI, Kench JG, Edwards S, Nair-Shalliker V, Smith DP. Descriptive analysis of prostate cancer pathology data from diagnosis and surgery in men from the 45 and Up Study. Pathology 2024; 56:39-46. [PMID: 38104002 DOI: 10.1016/j.pathol.2023.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 08/12/2023] [Accepted: 09/19/2023] [Indexed: 12/19/2023]
Abstract
Information available from the New South Wales Cancer Registry (NSWCR) about the aggressiveness of prostate cancer is limited to the summary stage variable 'degree of spread', which contains a high proportion of cases defined as 'unknown'. In this study we demonstrate the feasibility of obtaining and analysing prostate cancer pathology data from stored pathology records. Pathology data were extracted from stored pathology records of incident prostate cancer cases in men participating in the 45 and Up Study, a large Australian prospective cohort study, who were diagnosed between January 2006 and December 2013. Baseline questionnaires from the 45 and Up Study were linked to the NSWCR. Demographic and pathology items were tabulated and associations described. We evaluated the completeness of pathological characteristics by degree of spread of cancer at diagnosis. Among the 123,921 men enrolled in the 45 and Up Study, 5,091 had incident prostate cancer and 5,085 were linked to a pathology record. The most complete variables included grade group of diagnostic (85.8%) and surgical (99.8%) specimens, margin status (98.1%), extraprostatic extension (95.1%) and seminal vesicle invasion (96.8%). Most diagnostic specimens were grade group 1 (26.6%) or 2 (23.5%). Of the 5,085 cases, 30.8% were classified by the NSWCR with unknown degree of spread; a pathology record could be extracted for 99.4% of these. The unknown degree of spread cases had similar levels of completeness and distribution of diagnostic and surgical pathology features to those with a localised degree of spread. This study demonstrated the feasibility of obtaining and analysing data derived from pathology reports from centralised state-based cancer registry notifications. Supplementing degree of spread information with pathology data from diagnosis and surgery will improve both the quality of research and policy aimed at improving the lives of men with prostate cancer.
Collapse
Affiliation(s)
- Benjamin D T Gallagher
- Faculty of Medicine and Health, Sydney School of Public Health, Camperdown, NSW, Australia; The Daffodil Centre, University of Sydney, Sydney, NSW, Australia.
| | - Karen Chiam
- Faculty of Medicine and Health, Sydney School of Public Health, Camperdown, NSW, Australia; The Daffodil Centre, University of Sydney, Sydney, NSW, Australia
| | - Albert Bang
- The Daffodil Centre, University of Sydney, Sydney, NSW, Australia
| | - Manish I Patel
- Department of Urology, Westmead Hospital, Specialty of Surgery, University of Sydney, Sydney, NSW, Australia
| | - James G Kench
- Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Sue Edwards
- Cancer Services and Information, Cancer Institute NSW, Sydney, NSW, Australia
| | - Visalini Nair-Shalliker
- The Daffodil Centre, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health Science, Macquarie University, Sydney, NSW, Australia
| | - David P Smith
- The Daffodil Centre, University of Sydney, Sydney, NSW, Australia; Menzies Health Institute Queensland, Griffith University, Southport, Qld, Australia; School of Public Health and Preventative Medicine, Monash University, Melbourne, Vic, Australia
| |
Collapse
|
|
7
|
Zazzara M, Gardiman MP, Dal Moro F. The bladder neck preservation in robot assisted radical prostatectomy: Surgical and pathological outcome. Arch Ital Urol Androl 2023; 95:12138. [PMID: 38193218 DOI: 10.4081/aiua.2023.12138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 11/30/2023] [Indexed: 01/10/2024] Open
Abstract
INTRODUCTION The post-prostatectomy incontinence is influenced by multiple elements, anatomic components and biological factors. The bladder neck preservation, more accurate during robot assisted radical prostatectomy, works on two anatomic components responsible for post-prostatectomy continence. The bladder neck preservation spares the internal sphincter, which is responsible for passive continence, and results in earlier return to continence and lower rates of post-prostatectomy incontinence. Moreover, this surgical technique spares the zone of urothelium coaptation and provides primary resistance to the urine to maintain postprostatectomy continence. The potential risk of bladder neck positive surgical margins (PSM) may prevent the usage of the bladder neck preservation. AIM The purpose of this study is to evaluate the surgical and pathological outcome in prostate cancer patients underwent robot assisted radical prostatectomy with bladder neck preservation. MATERIALS AND METHODS Prospectively, we have collected demographic, clinical, surgical and pathological data of prostate cancer patients underwent robot assisted radical prostatectomy with bladder neck preservation, from January 2014 to December 2016, in Urological Clinic of the University of Padua. Moreover, it was valued the presence of alterations or continuous solutions of specimen external capsule, attributable to the surgical technique of bladder neck preservation, by microscopic and macroscopic pathological analysis. RESULTS According to D'Amico risk classification, 40 patients (45.4%) had a low risk neoplasia, 35 patients (39.8%) had an intermediate risk neoplasia, 13 patients (14.8%) had an high risk neoplasia. The median prostatic volume, valued on specimen, was 30.84 cc (21.5-44.75 cc). The median prostatic weight, valued on specimen, was 51 gr (36-67 gr). The pathological stage of disease was pT2a in 11 cases (12.5%), pT2b in 37 cases (42.1%), pT3a in 28 cases (31.8%), pT3b in 12 cases (13.6%). The pathological stage of lymph node involvement was pNx in 17 cases (19.3%), pN0 in 66 cases (75%), pN1 in 5 cases (5.7%). The prostate cancers diagnosed had a Gleason score at specimen of 6 in 10 cases (10.4%), 7 (3+4) in 30 cases (34.1%), 7 (4+3) in 20 cases (22.7%), 8 in 19 cases (21.6%) and 9 in 9 cases (10.2%). The prostatic base was involved by neoplasia in 14 patients (15.9%); of these, 5 patients (35.7%) had bladder neck PSM. The patients with bladder neck PSM had: a pathological stage of disease as pT3a in 2 cases (40%) and pT3b in 3 cases (60%); a pathological stage of lymph node involvement as pN0 in 2 cases (40%) and pN1 in 3 cases (60%); a Gleason score at specimen of 8 in 3 cases (60%) and 9 in 2 cases (40%); multiple PSM. Nobody had alterations or continuous solutions of specimen external capsule, attributable to surgical technique of bladder neck preservation. CONCLUSIONS The bladder neck preservation, during robot assisted radical prostatectomy, is a safe oncological procedure resulting in a good functional outcome, about post-prostatectomy continence, working on two anatomic components responsible for post-prostatectomy continence. The bladder neck PSM are linked to neoplasia with adverse pathological features, rather than the bladder neck preservation.
Collapse
Affiliation(s)
- Michele Zazzara
- Urology Clinic, Department of Surgical Oncological and Gastroenterological Sciences, University of Padua, Padua.
| | - Marina P Gardiman
- Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, Padua.
| | - Fabrizio Dal Moro
- Urology Clinic, Department of Surgical Oncological and Gastroenterological Sciences, University of Padua, Padua.
| |
Collapse
|
|
8
|
Takahashi K, Nishikawa K, Tanishima Y, Ishikawa Y, Kurogochi T, Yuda M, Matsumoto A, Yano F, Ikegami T, Eto K. Anatomical and anastomotic viability indexes for stratifying the risk of anastomotic leakage in esophagectomy with retrosternal reconstruction. Ann Gastroenterol Surg 2023; 7:896-903. [PMID: 37927915 PMCID: PMC10623953 DOI: 10.1002/ags3.12693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/17/2023] [Accepted: 05/03/2023] [Indexed: 11/07/2023] Open
Abstract
Background Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction. Methods This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model. Results According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P < 0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P < 0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P < 0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%]). Conclusion The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction.
Collapse
Affiliation(s)
- Keita Takahashi
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Katsunori Nishikawa
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Yuichiro Tanishima
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Yoshitaka Ishikawa
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Takanori Kurogochi
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Masami Yuda
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Akira Matsumoto
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Fumiaki Yano
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Toru Ikegami
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| | - Ken Eto
- Department of Gastrointestinal SurgeryJikei University School of MedicineTokyoJapan
| |
Collapse
|
|
9
|
Zheng Y, Li X, Deng S, Zhao H, Ye Y, Zhang S, Huang X, Bai R, Zhuang L, Zhou Q, Li M, Su J, Li R, Bao X, Zeng L, Chen R, Zheng J, Lin D, He C, Zhang J, Zuo Z. CSTF2 mediated mRNA N 6-methyladenosine modification drives pancreatic ductal adenocarcinoma m 6A subtypes. Nat Commun 2023; 14:6334. [PMID: 37816727 PMCID: PMC10564946 DOI: 10.1038/s41467-023-41861-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 09/21/2023] [Indexed: 10/12/2023] Open
Abstract
N6-methyladenosine (m6A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m6A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m6A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m6A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m6A regulator CSTF2 that co-transcriptionally regulates m6A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m6As have positive effects on the RNA level of host genes, and CSTF2-regulated m6As are mainly recognized by IGF2BP2, an m6A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.
Collapse
Affiliation(s)
- Yanfen Zheng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xingyang Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shuang Deng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hongzhe Zhao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Ye
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shaoping Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xudong Huang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ruihong Bai
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lisha Zhuang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Quanbo Zhou
- Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mei Li
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiachun Su
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Rui Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaoqiong Bao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lingxing Zeng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Rufu Chen
- Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jian Zheng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Dongxin Lin
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
- Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Chuan He
- Department of Chemistry, The University of Chicago, Chicago, IL, USA.
- Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA.
- Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
| | - Jialiang Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Zhixiang Zuo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
| |
Collapse
|
|
10
|
Wu G, Su J, Zeng L, Deng S, Huang X, Ye Y, Li R, Bai R, Zhuang L, Li M, Zhou Q, Zheng Y, Deng J, Zhang S, Chen R, Lin D, Zhang J, Zheng J. LncRNA BCAN-AS1 stabilizes c-Myc via N 6-methyladenosine-mediated binding with SNIP1 to promote pancreatic cancer. Cell Death Differ 2023; 30:2213-2230. [PMID: 37726400 PMCID: PMC10589284 DOI: 10.1038/s41418-023-01225-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/21/2023] Open
Abstract
C-Myc overexpression contributes to multiple hallmarks of human cancer but directly targeting c-Myc is challenging. Identification of key factors involved in c-Myc dysregulation is of great significance to develop potential indirect targets for c-Myc. Herein, a collection of long non-coding RNAs (lncRNAs) interacted with c-Myc is detected in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, lncRNA BCAN-AS1 is identified as the one with highest c-Myc binding enrichment. BCAN-AS1 was abnormally elevated in PDAC tumors and high BCAN-AS1 level was significantly associated with poor prognosis. Mechanistically, Smad nuclear-interacting protein 1 (SNIP1) was characterized as a new N6-methyladenosine (m6A) mediator binding to BCAN-AS1 via recognizing its m6A modification. m6A-modified BCAN-AS1 acts as a scaffold to facilitate the formation of a ternary complex together with c-Myc and SNIP1, thereby blocking S phase kinase-associated protein 2 (SKP2)-mediated c-Myc ubiquitination and degradation. Biologically, BCAN-AS1 promotes malignant phenotypes of PDAC in vitro and in vivo. Treatment of metastasis xenograft and patient-derived xenograft mouse models with in vivo-optimized antisense oligonucleotide of BCAN-AS1 effectively represses tumor growth and metastasis. These findings shed light on the pro-tumorigenic role of BCAN-AS1 and provide an innovant insight into c-Myc-interacted lncRNA in PDAC.
Collapse
Affiliation(s)
- Guandi Wu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jiachun Su
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Clinical Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lingxing Zeng
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shuang Deng
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xudong Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Ye
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Rui Li
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ruihong Bai
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lisha Zhuang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Mei Li
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Quanbo Zhou
- Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanfen Zheng
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Junge Deng
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shaoping Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Rufu Chen
- Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Dongxin Lin
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Jialiang Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
| | - Jian Zheng
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
| |
Collapse
|
|
11
|
Lv B, Cheng X, Xie Y, Cheng Y, Yang Z, Wang Z, Jin E. Predictive value of lesion morphology in rectal cancer based on MRI before surgery. BMC Gastroenterol 2023; 23:318. [PMID: 37726671 PMCID: PMC10510204 DOI: 10.1186/s12876-023-02910-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 08/02/2023] [Indexed: 09/21/2023] Open
Abstract
OBJECTIVE To explore the relationship of MRI morphology of primary rectal cancer with extramural vascular invasion (EMVI), metastasis and local recurrence. MATERIALS AND METHODS This retrospective study included 153 patients with rectal cancer. Imaging factors and histopathological index including nodular projection (NP), cord sign (CS) at primary tumor margin, irregular nodules (IN) of mesorectum, MRI-detected peritoneal reflection invasion (PRI), range of rectal wall invasion (RRWI), patterns and length of tumor growth, maximal extramural depth (EMD), histologically confirmed local node involvement (hLN), MRI T stage, MRI N stage, MRI-detected extramural vascular invasion (mEMVI) and histologically confirmed extramural vascular invasion (hEMVI) were evaluated. Determining the relationship between imaging factors and hEMVI, synchronous metastasis and local recurrence by univariate analysis and multivariable logistic regression, and a nomogram validated internally via Bootstrap self-sampling was constructed based on the latter. RESULTS Thirty-eight cases of hEMVI, fourteen cases of synchronous metastasis and ten cases of local recurrence were observed among 52 NP cases. There were 50 cases of mEMVI with moderate consistency with hEMVI (Kappa = 0.614). NP, CS, EMD and mEMVI showed statistically significant differences in the negative and positive groups of hEMVI, synchronous metastasis, and local recurrence. Compared to patients with local mass growth, the rectal tumor with circular infiltration had been found to be at higher risk of synchronous metastasis and local recurrence (P < 0.05). NP and IN remained as significant predictors for hEMVI, and mEMVI was a predictor for synchronous metastasis, while PRI and mEMVI were predictors for local recurrences. The nomogram for predicting hEMVI demonstrated a C-index of 0.868, sensitivity of 86.0%, specificity of 79.6%, and accuracy of 81.7%. CONCLUSION NP, CS, IN, large EMD, mEMVI, and circular infiltration are significantly associated with several adverse prognostic indicators. The nomogram based on NP has good predictive performance for preoperative EMVI. mEMVI is a risk factor for synchronous metastasis. PRI and mEMVI are risk factors for local recurrence.
Collapse
Affiliation(s)
- Baohua Lv
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong-an Road, Beijing, 100050, China
- Department of Radiology, Taian City Central Hospital, Tai'an, 271099, China
| | - Xiaojuan Cheng
- Clinical Skills Center, Taian City Central Hospital, Tai'an, 271099, China
| | - Yuanzhong Xie
- Department of Radiology, Taian City Central Hospital, Tai'an, 271099, China
| | - Yanling Cheng
- Respiratory department of Shandong second rehabilitation hospital, Tai'an, 271000, China
| | - Zhenghan Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong-an Road, Beijing, 100050, China
| | - Zhenchang Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong-an Road, Beijing, 100050, China
| | - Erhu Jin
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong-an Road, Beijing, 100050, China.
| |
Collapse
|
|
12
|
Lv B, Cheng X, Cheng Y, Kong X, Jin E. Predictive value of MRI-detected tumor deposits in locally advanced rectal cancer. Front Oncol 2023; 13:1153566. [PMID: 37671062 PMCID: PMC10476949 DOI: 10.3389/fonc.2023.1153566] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 08/03/2023] [Indexed: 09/07/2023] Open
Abstract
Background Although tumor deposits (TDs) are not the same as lymph nodes, the prognosis of patients with TDs is similar or worse than that of patients with metastatic lymph nodes. TDs are mostly assessed by the histology of samples after surgery, thus, not helpful for preoperative treatment strategies. The primary objective of this study was to detect TDs by MRI and evaluate its predictive value. Materials and methods A total of 114 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including MRI- detected TDs (mTDs), tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (mEMVI), MRI-detected lymph node metastasis (mLN), MRI T stage, MRI N stage, the range of rectal wall involved by the tumor, peritoneal reflection invasion, tumor length, tumor location, cord sign at the tumor edge, nodular protrusion at the tumor edge, maximal extramural depth and pathology-proven lymph node involvement (pLN) were evaluated. The correlation of MRI factors with postoperative distant metastasis (PDM) and pLN were analyzed by univariate analysis and multivariate logistic regression analysis, and nomograms were established based on the latter. The diagnostic efficiency was evaluated by the receiver operating characteristic curve (ROC) and area under the curve (AUC). Results A total of 38 cases of pLN, 13 of PDM and 17 of pathology-proven TDs (pTDs) were found. Ten cases of PDM and 22 cases of pLN in 30 mTDs cases were also found. Chi-square test showed that mTDs, mLN, TBC, mEMVI, MRI T stage, nodular protrusion, cord sign, maximal extramural depth and peritoneal reflection invasion were correlated with PDM and pLN (P<0.05). mTDs and peritoneal reflection invasion were independent risk factors for PDM (odds ratio: 10.15 and 8.77, P<0.05), mTDs and mLN were independent risk factors for pLN (odds ratio: 5.50 and 5.91, P<0.05), and Hosmer-Lemeshow test showed that the results of two models were not statistically significant, suggesting that the fit was good. On this basis, two nomograms for predicting PDM and pLN were confirmed by Bootstrap self-sampling, and the C-indices of the two nomograms were 0.837 and 0.817, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PDM and pLN was good. The DeLong test showed that the predictive efficiency of the nomogram in predicting pLN was better than that of mLN (P=0.0129). Conclusion mTDs are a risk factor for PDM and lymph node metastasis. The two nomograms based on mTDs showed a good performance in predicting PDM and lymph node metastasis, possessing a certain clinical value.
Collapse
Affiliation(s)
- Baohua Lv
- Department of Radiology, Taian City Central Hospital, Qingdao University, Tai’an, China
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaojuan Cheng
- Clinical Skills Center, Taian Central Hospital, Tai’an, China
| | - Yanling Cheng
- Respiratory Department, Shandong Second Rehabilitation Hospital, Tai’an, China
| | - Xue Kong
- Department of Radiology, Taian City Central Hospital, Qingdao University, Tai’an, China
| | - Erhu Jin
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
13
|
Ushimaru Y, Makino T, Tanaka K, Yamashita K, Saito T, Yamamoto K, Takahashi T, Kurokawa Y, Nakajima K, Morii E, Eguchi H, Doki Y. Clinical Significance of Intramural Metastasis as an Independent Prognostic Factor in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2023; 30:5195-5202. [PMID: 37273025 PMCID: PMC10319648 DOI: 10.1245/s10434-023-13464-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 03/22/2023] [Indexed: 06/06/2023]
Abstract
BACKGROUND Although intramural metastasis (IM) in esophageal cancer is considered a poor prognostic factor, there are only limited reports detailing its clinicopathologic characteristics and prognostic impact. PATIENTS AND METHODS We retrospectively included patients with esophageal squamous cell carcinoma (ESCC) with esophagectomy at our institution between 2010 and 2016. We compared patients with intramural metastases (IMs) (IM group) versus those without IMs (non-IM group) to clarify the clinical significance of intramural metastasis in ESCC. RESULTS A total of 23 (3.9%) out of all 597 patients were identified to have IM. The IMs were located on the cranial side in 13 (56.5%) and caudal side in 10 (43.5%) of the primary tumor, with two multiple cases. The IM group, compared with the non-IM group, was associated with higher percentage of cN-positive (91.3 versus 67.9%, P = 0.02), pN-positive (82.6 versus 55.9%, P = 0.04), and pM(lym)-positive (30.4 versus 12.5%, P = 0.02) cases. Five-year recurrence-free survival (RFS) was significantly worse in the IM group than the non-IM group (14.9 versus 55.0 %, P < 0.001). Multivariable analysis of recurrence-free survival identified pT (HR 1.74, 95% CI 1.36-2.23, P < 0.001), pN (HR 2.11, 95% CI 1.60-2.78, P < 0.001), histological classification (HR 1.68, 95% CI 1.21-2.35, P = 0.002), and pM(LYM) (HR 1.64, 95% CI 1.64-2.95, P < 0.001), along with presence of IM (HR 2.24, 95% CI 1.37-3.64, P < 0.001) to be independent prognostic factors. Lymphatic (65.2 versus 24.9%, P < 0.001) and hepatic (26.1 versus 6.8%, P = 0.005) recurrences were significantly more common in the IM group than in the non-IM group. CONCLUSIONS IM was shown to be associated with dismal survival after surgery. A treatment strategy emphasizing more intensive systemic control should be considered for patients with ESCC with IM.
Collapse
Affiliation(s)
- Yuki Ushimaru
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takuro Saito
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuyoshi Yamamoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| |
Collapse
|
|
14
|
Creemers SG, Van Santvoort B, van den Berkmortel FWPJ, Kiemeney LA, van Oort IM, Aben KKH, Hamberg P. Role of multidisciplinary team meetings in implementation of chemohormonal therapy in metastatic prostate cancer in daily practice. Prostate Cancer Prostatic Dis 2023; 26:133-141. [PMID: 35798856 DOI: 10.1038/s41391-022-00556-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 04/20/2022] [Accepted: 05/27/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The recommended treatment for a subset of patients with metastatic prostate cancer (mPC) changed from androgen deprivation therapy (ADT) to combinations with chemotherapy such as docetaxel. Implementation of new evidence from trials is however complex and challenging. We investigated the effect of multidisciplinary team meetings (MDTs) on adopting the newest emerging combination therapy in patients with mPC and assessed the overall survival of chemohormonal therapy in a real-world setting. METHODS All mPC patients diagnosed between October 2015 and April 2016 in the Netherlands were identified from the population-based Netherlands Cancer Registry (n = 962). Logistic regression analyses were performed to examine the role of patient- and tumor characteristics, with special emphasis on MDTs, on receiving chemohormonal therapy versus ADT monotherapy. Kaplan-Meier survival curves were used to assess overall survival (OS). RESULTS As many patients received ADT monotherapy as chemohormonal therapy (both n = 452). Being discussed in a MDT as patient, younger age, less comorbidities, a better performance status and high-volume disease were significantly associated with receiving chemohormonal therapy compared to ADT monotherapy. After adjustment for these factors, the presence of a MDT was independently associated with the administration of chemohormonal therapy (OR 2.77, 95% CI 1.68-4.59). The 2-year OS was 82.1% (95% CI: 78.5-85.6%) for patients receiving chemohormonal therapy and 59.9% (95% CI: 55.4-64.4%) for patients receiving ADT monotherapy. CONCLUSION Being discussed in a MDT is independently associated with the administration of chemohormonal therapy in this group of patients with mPC. This supports the hypothesis that implementation of innovative treatment options is facilitated by an organizational structure with MDTs.
Collapse
Affiliation(s)
- S G Creemers
- Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, the Netherlands.
| | - B Van Santvoort
- Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | | | - L A Kiemeney
- Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands
- Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands
| | - I M van Oort
- Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - K K H Aben
- Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands
| | - P Hamberg
- Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, the Netherlands
| |
Collapse
|
|
15
|
He X, Fan R, Sun J, Ren Y, Zhao X, Rui W, Yuan Y, Zou D. A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm. Front Oncol 2023; 13:1087852. [PMID: 36761937 PMCID: PMC9902908 DOI: 10.3389/fonc.2023.1087852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
Background/Objectives There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.
Collapse
Affiliation(s)
- Xiangyi He
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Fan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Sun
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanhao Ren
- School of Mathematical Sciences, Fudan University, Shanghai, China
| | - Xuesong Zhao
- Departments of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Rui
- Departments of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
| |
Collapse
|
|
16
|
Tominaga T, Nonaka T, Oyama S, Takamura Y, Hashimoto S, Shiraishi T, Sawai T, Nagayasu T. Efficacy of Neutrophil-to-Lymphocyte Ratio for Cancer-Specific Survival in Elderly Patients with Localized Colon Cancer: A Single Center Propensity Score-Matched Analysis. Clin Exp Gastroenterol 2023; 16:1-9. [PMID: 36636228 PMCID: PMC9830562 DOI: 10.2147/ceg.s385207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 11/22/2022] [Indexed: 01/06/2023] Open
Abstract
Purpose The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been studied for colorectal cancer. Elderly patients in general tend to have comorbidities and decreased organ function that potentially influence the NLR score. The aim of this study was to investigate the relationship between NLR and cancer-specific survival in elderly patients with colon cancer, using a propensity score-matched analysis. Patients and Methods A total of 203 patients aged over 75 years who underwent curative resection for colon cancer and were diagnosed pathologically with stage II/III disease were eligible for entry to the study. Patients were divided into two groups according to NLR score: NLR-High (NLR≥4.5) group (NLR-H, n=60) and NLR-Low (NLR<4.5) group (NLR-L, n=143). After propensity score matching, 57 patients in each group were matched. Results Before matching, Charlson comorbidity index was significantly higher in the NLR-H group (4 vs 2, p<0.001). After matching, all factors were similar between the groups. The median follow-up period was 43 months (range, 1-160 months). Five-year relapse-free-survival (69.8% vs 87.3%, p=0.030) and cancer-specific survival (83.0% vs 96.0%, p=0.042) were significantly lower in the NLR-H group. Conclusion NLR appears to be a cancer-specific prognostic marker in elderly patients with colon cancer.
Collapse
Affiliation(s)
- Tetsuro Tominaga
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan,Correspondence: Tetsuro Tominaga, Department of Surgical Oncology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan, Tel +81-95-819-7304, Fax +81-95-819-7306, Email
| | - Takashi Nonaka
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Shosaburo Oyama
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Yuma Takamura
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Shintaro Hashimoto
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Toshio Shiraishi
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Terumitsu Sawai
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Takeshi Nagayasu
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| |
Collapse
|
|
17
|
Yamamoto H, Soh J, Okumura N, Suzuki H, Nakata M, Fujiwara T, Gemba K, Sano I, Fujinaga T, Kataoka M, Terazaki Y, Fujimoto N, Kataoka K, Kosaka S, Yamashita M, Inokawa H, Inoue M, Nakamura H, Yamashita Y, Hotta K, Yoshioka H, Morita S, Matsuo K, Sakamoto J, Date H, Toyooka S. Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201. PLoS One 2023; 18:e0285273. [PMID: 37205678 DOI: 10.1371/journal.pone.0285273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 04/12/2023] [Indexed: 05/21/2023] Open
Abstract
BACKGROUND It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.
Collapse
Affiliation(s)
- Hiromasa Yamamoto
- Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan
| | - Junichi Soh
- Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Norihito Okumura
- Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan
| | - Hiroyuki Suzuki
- Department of Chest Surgery, Fukushima Medical University Hospital, Fukushima, Japan
| | - Masao Nakata
- Department of General Thoracic Surgery, Kawasaki Medical School Hospital, Kurashiki, Japan
| | - Toshiya Fujiwara
- Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Kenichi Gemba
- Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan
| | - Isao Sano
- Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Takuji Fujinaga
- Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center, Gifu, Japan
| | - Masafumi Kataoka
- Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Yasuhiro Terazaki
- Department of Respiratory Surgery, Saga-Ken Medical Centre Koseikan, Saga, Japan
| | - Nobukazu Fujimoto
- Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan
| | - Kazuhiko Kataoka
- Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Shinji Kosaka
- Department of Thoracic Surgery, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Motohiro Yamashita
- Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Hidetoshi Inokawa
- Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan
| | - Masaaki Inoue
- Department of Chest Surgery, Shimonoseki City Hospital, Shimonoseki, Japan
| | - Hiroshige Nakamura
- Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan
| | - Yoshinori Yamashita
- Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan
| | - Katsuyuki Hotta
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Hiroshige Yoshioka
- Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
- Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
| | | | - Hiroshi Date
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Shinichi Toyooka
- Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan
| |
Collapse
|
|
18
|
Westerberg M, Beckmann K, Gedeborg R, Irenaeus S, Holmberg L, Garmo H, Stattin P. Choice of imputation method for missing metastatic status affected estimates of metastatic prostate cancer incidence. J Clin Epidemiol 2022; 155:22-30. [PMID: 36538980 DOI: 10.1016/j.jclinepi.2022.12.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 12/07/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
Abstract
OBJECTIVES To study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer. STUDY DESIGN AND SETTING Estimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage. RESULTS The proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage. CONCLUSIONS Plausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI.
Collapse
Affiliation(s)
- Marcus Westerberg
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Mathematics, Uppsala University, Uppsala, Sweden.
| | - Kerri Beckmann
- Cancer Epidemiology and Population Health Research Group, Allied Health and Human Performance, University of South Australia, Adelaide, Australia
| | - Rolf Gedeborg
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Sandra Irenaeus
- Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden; Regional Cancer Center, Uppsala University/Uppsala University Hospital, Uppsala, Sweden
| | - Lars Holmberg
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Hans Garmo
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Regional Cancer Center, Uppsala University/Uppsala University Hospital, Uppsala, Sweden
| | - Pär Stattin
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
19
|
Takahashi K, Nishikawa K, Tanishima Y, Ishikawa Y, Kobayashi T, Masuda T, Kurogochi T, Yuda M, Tanaka Y, Matsumoto A, Yano F, Eto K. Risk stratification of anastomotic stricture using early postoperative endoscopic and computed tomography findings in patients undergoing esophagectomy with cervical esophagogastric anastomosis for esophageal cancer. Dis Esophagus 2022; 35:6530218. [PMID: 35178563 DOI: 10.1093/dote/doac004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 12/13/2021] [Indexed: 12/11/2022]
Abstract
Anastomotic stricture (AS) is one of the major complications after esophagectomy for esophageal cancer. We have previously reported that severe mucosal degeneration (MD) of the anastomotic site was associated with the incidence of AS. Meanwhile, there are few reports to correlate anastomotic internal circumference (AIC) with computed tomography (CT) with the incidence of AS. Therefore, this study was conducted to clarify the correlation of early postoperative endoscopic and CT findings with the incidence of AS. We assessed 205 patients who underwent esophagectomy. We then divided them into the non-AS group (n = 164) and the AS group (n = 41) and compared their background data and intraoperative and postoperative outcomes. We also evaluated the risk factors for AS using logistic regression model. Multivariate analysis revealed small AIC (P = 0.003; OR = 4.400; 95% CI = 1.650-11.700) and severe MD (P < 0.001; OR = 7.200; 95% CI = 2.650-19.600) as the independent risk factors for AS development. We also stratified the patients into the following four groups according to the incidence of AS: low-risk (normal AIC and intact or mild MD, 6.2%), intermediate-risk (small AIC and intact or mild MD, 29.4%), high-risk (normal AIC and severe MD, 42.9%), and very high-risk (small AIC and severe MD, 61.1%). Early postoperative endoscopic and CT findings were useful in predicting the development of AS after esophagectomy.
Collapse
Affiliation(s)
- Keita Takahashi
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Katsunori Nishikawa
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Yuichiro Tanishima
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Yoshitaka Ishikawa
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Takehiro Kobayashi
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Masuda
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Takanori Kurogochi
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Masami Yuda
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Yujiro Tanaka
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Akira Matsumoto
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Fumiaki Yano
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Ken Eto
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
20
|
Alafnan A, Seetharam AA, Hussain T, Gupta MS, Rizvi SMD, Moin A, Alamri A, Unnisa A, Awadelkareem AM, Elkhalifa AO, Jayahanumaiah P, Khalid M, Balashanmugam N. Development and Characterization of PEGDA Microneedles for Localized Drug Delivery of Gemcitabine to Treat Inflammatory Breast Cancer. MATERIALS (BASEL, SWITZERLAND) 2022; 15:ma15217693. [PMID: 36363283 PMCID: PMC9658843 DOI: 10.3390/ma15217693] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 10/19/2022] [Accepted: 10/24/2022] [Indexed: 05/14/2023]
Abstract
Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only.
Collapse
Affiliation(s)
- Ahmed Alafnan
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia; (A.A.); (A.A.)
| | - Aravindram Attiguppe Seetharam
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Sri Shivarathreeshwara Nagar, Mysore 570015, India;
| | - Talib Hussain
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia; (A.A.); (A.A.)
- Correspondence: (T.H.); (M.S.G.)
| | - Maram Suresh Gupta
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Sri Shivarathreeshwara Nagar, Mysore 570015, India;
- Correspondence: (T.H.); (M.S.G.)
| | - Syed Mohd Danish Rizvi
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia; (S.M.D.R.); (A.M.)
| | - Afrasim Moin
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia; (S.M.D.R.); (A.M.)
| | - Abdulwahab Alamri
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia; (A.A.); (A.A.)
| | - Aziz Unnisa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia;
| | - Amir Mahgoub Awadelkareem
- Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha’il, Ha’il 81442, Saudi Arabia; (A.M.A.); (A.O.E.)
| | - AbdElmoneim O. Elkhalifa
- Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha’il, Ha’il 81442, Saudi Arabia; (A.M.A.); (A.O.E.)
| | - Pradyumna Jayahanumaiah
- Central Manufacturing Technology Institute (CMTI), Tumkur Road, Bangaluru 560022, India; (P.J.); (N.B.)
| | - Mohammad Khalid
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;
| | - Natchimuthu Balashanmugam
- Central Manufacturing Technology Institute (CMTI), Tumkur Road, Bangaluru 560022, India; (P.J.); (N.B.)
| |
Collapse
|
|
21
|
Villarreal-García V, Estupiñan-Jiménez JR, Vivas-Mejía PE, Gonzalez-Villasana V, Vázquez-Guillén JM, Reséndez-Pérez D. A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs. Front Oncol 2022; 12:980694. [PMID: 36226048 PMCID: PMC9548555 DOI: 10.3389/fonc.2022.980694] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/05/2022] [Indexed: 11/28/2022] Open
Abstract
Breast cancer (BC) is the most common cancer in women worldwide. This highly heterogeneous disease is molecularly stratified into luminal A, luminal B, HER2, triple-negative/basal-like, and normal-like subtypes. An important aspect in BC progression is the activation of inflammatory processes. The activation of CD8+/Th1, NK, and M1 tumor associated macrophages (TAMs), leads to tumor destruction. In contrast, an anti-inflammatory response mediated by CD4+/Th2 and M2 TAMs will favor tumor progression. Inflammation also stimulates the production of inflammatory mediators like reactive oxygen species (ROS). In chronic inflammation, ROS activates oxidative stress and endothelial dysfunction. In cancer, ROS plays a dual role with anti-tumorigenic and pro-tumorigenic effects in cell signaling pathways that control proliferation, survival, apoptosis, and inflammation. MicroRNAs (miRNAs), which are known to be involved in BC progression and inflammation, can be regulated by ROS. At the same time, miRNAs regulate the expression of genes modulating oxidative stress. In this review, we will discuss the interplay between inflammation, ROS, and miRNAs as anticancer and tumor promoter molecules in BC. A clear understanding of the role of miRNAs in the regulation of ROS production and inflammation, may lead to new opportunities for therapy in BC.
Collapse
Affiliation(s)
- Valeria Villarreal-García
- Departmento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - José Roberto Estupiñan-Jiménez
- Departmento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Pablo E. Vivas-Mejía
- Department of Biochemestry, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
- Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
| | - Vianey Gonzalez-Villasana
- Departmento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - José Manuel Vázquez-Guillén
- Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Diana Reséndez-Pérez
- Departmento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
- Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| |
Collapse
|
|
22
|
Gao H, Zhou H, Gao Y, He L, Li W, Xu M, Feng H, Feng X, Qiu C. Establishment of a new cell line of canine inflammatory mammary cancer: IMC-118. Vet Comp Oncol 2022; 20:679-687. [PMID: 35429113 DOI: 10.1111/vco.12822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 04/13/2022] [Accepted: 04/13/2022] [Indexed: 11/30/2022]
Abstract
Canine inflammatory mammary cancer (IMC) has long been regarded as an attractive animal model for research into human inflammatory breast cancer (IBC), Although some canine mammary tumour cell lines corresponding to human mammary cancer cell lines have been established, there is still a need to supplement the canine mammary tumour cell bank. The goal of this study was to create a new type of IMC cell line. The primary tumour, IMC-118, was identified as IMC by pathology examination. Immunohistochemistry analysis revealed negative immunoreactivity to oestrogen receptor (ER), but positive immunoreactivity to progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2). Immunofluorescence (IF) analysis revealed that the IMC-118 cell line from this primary tumour was negative for ER but positive for PR and HER-2, and was also positive for epithelial and mesenchymal cell markers. This cell line was cultured stably for more than 50 passages and grew well after cryopreservation. In vivo, tumour masses and metastases in the lungs were discovered after inoculating the IMC-118 cells into the nude mice model. As a result, a novel canine IMC cell line, IMC-118, was effectively established, and could be employed as a promising model for immunotherapy and epithelial-mesenchymal transition mechanism of IMC research in both dogs and humans.
Collapse
Affiliation(s)
- Hongbo Gao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Han Zhou
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Yiming Gao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Lixin He
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Wenxuan Li
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Meixia Xu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Huili Feng
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Xiujuan Feng
- Nanjing Police Dog Research Institute of the Ministry of the Public Security, Nanjing, China
| | - Changwei Qiu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| |
Collapse
|
|
23
|
Ward K, Kitchen MO, Mathias SJ, Khanim FL, Bryan RT. Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning. Front Surg 2022; 9:912438. [PMID: 35959122 PMCID: PMC9360612 DOI: 10.3389/fsurg.2022.912438] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/07/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction Non-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC. Methods PubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included. Results Novel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations. Conclusions Novel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages.
Collapse
Affiliation(s)
- Kelly Ward
- The Bladder Cancer Research Centre, University of Birmingham, Birmingham, United Kingdom
| | - Mark O Kitchen
- School of Medicine, Keele University, Stoke-on-Trent, United Kingdom
| | - Suresh-Jay Mathias
- New Cross Hospital, The Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | - Farhat L Khanim
- The Bladder Cancer Research Centre, University of Birmingham, Birmingham, United Kingdom
| | - Richard T Bryan
- The Bladder Cancer Research Centre, University of Birmingham, Birmingham, United Kingdom
| |
Collapse
|
|
24
|
Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study. Eur Radiol 2022; 33:233-243. [PMID: 35771248 DOI: 10.1007/s00330-022-08962-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 04/24/2022] [Accepted: 06/11/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Minimal extrathyroid extension (mETE) was removed from the TNM staging system. This study was designed prospectively to compare the safety and efficacy of microwave ablation (MWA) versus surgery for treating T1N0M0 papillary thyroid carcinomas (PTC) with sonographically detected mETE. METHODS From December 2019 to April 2021, 198 patients with T1N0M0 mETE-PTCs evaluated by preoperative ultrasound from 10 hospitals were included. Ninety-two patients elected MWA, and 106 patients elected surgery for treatment. MWA was performed using extensive ablation with hydrodissection. Surgery consisted of lobectomy with ipsilateral central lymph node dissection (CLD), lobe and isthmus excision with ipsilateral CLD and total thyroidectomy with ipsilateral CLD. The rates of technical success, cost, oncologic outcomes, complications and quality of life of the two groups were assessed. RESULTS The follow-up times for the MWA and surgery groups were 12.7 ± 4.1 and 12.6 ± 5.0 months, respectively. The technical success rate was 100% for both groups. Oncological outcomes of the two groups were similar during the follow-up (all p > 0.05). The MWA group had a shorter operation time, less blood loss and lower costs (all p < 0.001). Three complications (3.3%) were reported in the MWA group and 4 (3.8%) in the surgery group (p = 0.846). The surgery group had higher scores for scar problems and anxiety (p < 0.001 and p = 0.003, respectively). CONCLUSIONS Microwave ablation was comparable in the short term to surgery in terms of treatment safety and efficacy in selected patients with T1N0M0 mETE-PTC detected by ultrasound. KEY POINTS • Microwave ablation is comparable to surgery in the safety and short-term efficacy for PTCs with sonographically detected mETE. • Thermal ablation is technically feasible for mETE-PTC treatment. • Patients with mETE-PTC have similar quality of life in the two groups, except for worse scar problems and anxiety in the surgery group.
Collapse
|
|
25
|
Chen B, Li R, Zhang J, Xu L, Jiang F. Genomic Landscape of Metastatic Lymph Nodes and Primary Tumors in Non-Small-Cell Lung Cancer. Pathol Oncol Res 2022; 28:1610020. [PMID: 35783357 PMCID: PMC9243222 DOI: 10.3389/pore.2022.1610020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 04/25/2022] [Indexed: 11/13/2022]
Abstract
Objective: To investigate the genetic mutation characteristics of non-small cell lung cancers (NSCLC) with and without lymph node metastasis.Methods: Primary lesions and metastatic lymph node lesions of 36 Chinese NSCLC patients were tested for somatic mutations, tumor mutation burden, phylogenetic and clonal evolutional analysis using a 1021-gene panel by next-generation sequencing (NGS) with an average sequencing depth of 671X.Results: In this study, eighteen patients with lung adenocarcinoma (LUAD) and 18 with lung squamous cell carcinoma (LUSC) were included. Different groups had distinct characteristics of gene mutations. CTNNB1 gene mutations were only present in Nome_LC LUAD patients (p < 0.05). ARID1A mutation was however the only gene with significant alterations (p < 0.05) in Nome_LC in LUSC. Phylogenetic trees of mutated genes were also constructed. Linear and parallel evolutions of metastatic lymph nodes were observed both in LUAD and LUSC.Conclusion: LUSC exhibited more genetic mutations than LUAD. Intriguingly, there was significant difference in gene mutations between Meta_LC and Nome_LC. CTNNB1 gene alteration was the key mutation in LUAD that seems to promote proliferation of the tumor and then determine T stage. On the other hand, proliferation of the tumor was characterized by ARID1A missense mutation in LUSC, thus influencing the T stage as well. Lymph node metastasis could display both linear and parallel evolutionary characteristics in NSCLC. Different metastatic lymph nodes might have exactly the same or different mutated genes, underlining the heterogeneous genomic characteristics of these cancer types.
Collapse
Affiliation(s)
- Bing Chen
- The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China
| | - Rutao Li
- The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China
| | - Junling Zhang
- The Medical Department, 3D Medicines Inc., Shanghai, China
| | - Lin Xu
- The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China
- *Correspondence: Lin Xu, ; Feng Jiang,
| | - Feng Jiang
- The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China
- *Correspondence: Lin Xu, ; Feng Jiang,
| |
Collapse
|
|
26
|
Straetmans JMJAA, Stuut M, Lacko M, Hoebers F, Speel EJM, Kremer B. Additional parameters to improve the prognostic value of the 8th edition of the UICC classification for human papillomavirus-related oropharyngeal tumors. Head Neck 2022; 44:1799-1815. [PMID: 35579041 PMCID: PMC9544856 DOI: 10.1002/hed.27084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 02/17/2022] [Accepted: 04/27/2022] [Indexed: 12/04/2022] Open
Abstract
Background The prognostic reliability of the UICC's TNM classification (8th edition) for human papillomavirus (HPV)‐positive tonsillar squamous cell carcinomas (TSCCs) compared to the 7th edition was explored, and its improvement by using additional anatomical and nonanatomical parameters. Methods One hundred and ten HPV‐positive and 225 HPV‐negative TSCCs were retrospectively analyzed. Survival was correlated with patient and tumor characteristics (7th and 8th edition UICC TNM classification). Results In HPV‐positive TSCCs, the 8th edition UICC's TNM classification correlated better with prognosis than the 7th edition. Also, smoking status was a stronger prognosticator of survival than UICC staging. Non‐ or former smokers had a 5‐year overall survival of 95.1% regardless of tumor stage. Furthermore, age (>65 years), cN3, and M1 classification were significant prognostic factors. Conclusion The prognostic value of the 8th edition UICC's TNM classification improved significantly when compared to the 7th edition. Nonetheless, further improvement is possible by adding nonanatomical factors (smoking, age >65 year) and separating N0‐N2 from N3.
Collapse
Affiliation(s)
- Jos M J A A Straetmans
- Department of Otorhinolaryngology and Head and Neck Surgery, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.,Department of Otorhinolaryngology and Head and Neck Surgery, Zuyderland Medical Center, Heerlen, the Netherlands
| | - Marijn Stuut
- Department of Otorhinolaryngology and Head and Neck Surgery, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Martin Lacko
- Department of Otorhinolaryngology and Head and Neck Surgery, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Frank Hoebers
- Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | - Ernst-Jan M Speel
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Bernd Kremer
- Department of Otorhinolaryngology and Head and Neck Surgery, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands
| |
Collapse
|
|
27
|
Felsenstein M, Lindhammer F, Feist M, Hillebrandt KH, Timmermann L, Benzing C, Globke B, Zocholl D, Hu M, Fehrenbach U, Sinn BV, Pelzer U, Sauer IM, Pratschke J, Malinka T. Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies? J Clin Med 2022; 11:2367. [PMID: 35566494 PMCID: PMC9103867 DOI: 10.3390/jcm11092367] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/13/2022] [Accepted: 04/20/2022] [Indexed: 12/16/2022] Open
Abstract
(1) Background: Perineural invasion (PNI) is a common characteristic of pancreatic ductal adenocarcinoma (PDAC) and is present in most resection margins. We hypothesized that curative pancreatic tumor resection with long-term survival could only be achieved in PNI-negative patients. (2) Material and Methods: A retrospective investigation of PDAC patients who underwent curative-intended surgery during the period 2008 to 2019 was performed at our institution. (3) Results: We identified 571 of 660 (86.5%) resected patients with well-annotated reports and complete datasets. Of those, 531 patients (93%) exhibited tumors with perineural invasion (Pn1), while 40 (7%) were negative for PNI (Pn0). The majority of patients in the Pn1 group presented advanced tumor stage and positive lymph node infiltration. Patients in the Pn0 group showed an improved disease-free and long-term survival compared to the Pn1 group (p < 0.001). Subgroup analysis of all R0-resected patients indicated improved long-term survival and disease-free survival of R0 Pn0 patients when compared to R0 Pn1 patients (p < 0.001). (4) Conclusion: Our study confirmed that Pn0 improves the long-term survival of PDAC-resected cancer patients. Furthermore, PNI significantly challenges the long-term survival of formally curative (R0) resected patients. We provide new insights into the dynamics of PNI in pancreatic cancer patients which are needed to define subgroups of patients for risk stratification and multimodal treatment strategies.
Collapse
Affiliation(s)
- Matthäus Felsenstein
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
- Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany
| | - Flora Lindhammer
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Mathilde Feist
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Karl Herbert Hillebrandt
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
- Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany
| | - Lea Timmermann
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Christian Benzing
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Brigitta Globke
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
- Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany
| | - Dario Zocholl
- Institute of Biometry and Clinical Epidemiology, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Mengwen Hu
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Uli Fehrenbach
- Department of Radiology, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Bruno Valentin Sinn
- Institute of Pathology, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Uwe Pelzer
- Medical Department, Division of Hematology, Oncology and Tumor Immunology, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Igor Maximillian Sauer
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
- Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| | - Thomas Malinka
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (F.L.); (M.F.); (K.H.H.); (L.T.); (C.B.); (B.G.); (M.H.); (I.M.S.); (J.P.)
| |
Collapse
|
|
28
|
Shao Y, Qi C, Yan J, Lu R, Ye G, Guo J. Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application. J Clin Lab Anal 2022; 36:e24369. [PMID: 35334500 PMCID: PMC9102612 DOI: 10.1002/jcla.24369] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/01/2022] [Accepted: 03/13/2022] [Indexed: 12/13/2022] Open
Abstract
Background Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. Methods Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan–Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. Results Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease‐free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease‐free survival time. The nomograms showed good accuracy of predicting survival time. Conclusion Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced‐stage patients.
Collapse
Affiliation(s)
- Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Changlei Qi
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Jianing Yan
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| |
Collapse
|
|
29
|
Twenty-Year Survival of Patients Operated on for Non-Small-Cell Lung Cancer: The Impact of Tumor Stage and Patient-Related Parameters. Cancers (Basel) 2022; 14:cancers14040874. [PMID: 35205621 PMCID: PMC8870355 DOI: 10.3390/cancers14040874] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/01/2022] [Accepted: 02/05/2022] [Indexed: 02/04/2023] Open
Abstract
Surgery is the mainstay treatment of non-small-cell lung cancer (NSCLC), but its impact on very-long-term survival (beyond 15 years) has never been evaluated. METHODS All patients operated on for major lung resection (Jun. 2001-Dec. 2002) for NSCL in the Thoracic Surgery Department at Paris-Hôtel-Dieu-University-Hospital were included. Patients' characteristics were prospectively collected. Vital status was obtained by checking INSEE database and verifying if reported as "non-death" by the hospital administrative database and direct phone interviews with patients of families. RESULTS 345 patients were included. The 15- and 20-year survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were: increasing age at surgery (p = 0.0042), lower BMI (p = 0.009), weight loss (p = 0.0034), higher CRP (p = 0.049), pathological stage (p = 0.00000042), and, among patients with adenocarcinoma, higher grade (p = 0.028). Increasing age (p = 0.004), cumulative smoking (p = 0.045), lower BMI (0.046) and pathological stage (p = 0.0026), were independent predictors of long-term survival at Cox multivariate analysis. In another model, increasing age (p = 0.013), lower BMI (p = 0.02), chronic bronchitis (p = 0.03), lower FEV1% (p = 0.00019), higher GOLD class of COPD (p = 0.0079), and pathological stage (p = 0.000024), were identified as independent risk factors. CONCLUSIONS Very-long-term survivals could be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determined longer outcomes suggesting that both initial tumor aggressiveness and host's characteristics act beyond the period usually taken into account in oncology.
Collapse
|
|
30
|
Lu F, Chen W, Jiang T, Cheng C, Wang B, Lu Z, Huang G, Qiu J, Wei W, Yang M, Huang X. Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma. Exp Ther Med 2022; 23:252. [PMID: 35261624 DOI: 10.3892/etm.2022.11177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 09/17/2021] [Indexed: 11/05/2022] Open
Affiliation(s)
- Fenying Lu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Weichang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Tingwang Jiang
- Department of Science and Technology Division, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Cuie Cheng
- Department of Gastroenterology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Bin Wang
- Department of Gastroenterology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Zhiping Lu
- Department of Gastroenterology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Guojin Huang
- Department of Gastroenterology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Jiaming Qiu
- Department of Pathology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Wei Wei
- Department of Pathology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Ming Yang
- Department of Thoracic Surgery, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| | - Xia Huang
- Department of Gastroenterology, The Second People's Hospital of Changshu, Suzhou, Jiangsu 215500, P.R. China
| |
Collapse
|
|
31
|
Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer. Sci Rep 2022; 12:599. [PMID: 35022469 PMCID: PMC8755713 DOI: 10.1038/s41598-021-04510-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Melanoma antigen gene (MAGE)-A6 and MAGE-A11 are two of the most cancer-testis antigens overexpressed in various types of cancers. However, the clinical and prognosis value of MAGE-A6 and MAGE-A11 co-expression in the pathophysiology of the bladder is unknown. Three studies were selected from GEO databases in order to introduce the common genes that are involved in bladder cancer. Then immunohistochemical analysis for staining pattern and clinicopathological significance of suggested markers, MAGE-A6 and MAGE-A11, were performed in 199 and 213 paraffin-embedded bladder cancer with long adjacent normal tissues, respectively. A significant and positive correlation was found between both nuclear and cytoplasmic expressions of MAGE-A6 as well as expression of cytoplasmic MAGE-A11 with histological grade, PT stage, lamina propria invasion, and LP/ muscularis (L/M) involvement (all of the p-values in terms of H-score were < 0.0001). Additionally, significant differences were found between both nuclear and cytoplasmic MAGE-A6/MAGE-A11 phenotypes with tumor size (P = 0.007, P = 0.043, respectively), different histological grades, PT stage, LP involvement, and L/M involvement (all of the p-values for both phenotypes were < 0.0001). The current study added the value of these novel markers to the bladder cancer clinical settlement that might be considered as an admirable target for immunotherapy.
Collapse
|
|
32
|
Wu C, Luo Y, Chen Y, Qu H, Zheng L, Yao J. Development of a prognostic gene signature for hepatocellular carcinoma. Cancer Treat Res Commun 2022; 31:100511. [PMID: 35030478 DOI: 10.1016/j.ctarc.2022.100511] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 02/08/2023]
Abstract
Accurate prediction of overall survival is important for prognosis and the assignment of appropriate personalized clinical treatment in hepatocellular carcinoma (HCC) patients. The aim of the present study was to establish an optimal gene model for the independent prediction of prognosis associated with common clinical patterns. Gene expression profiles and the corresponding clinical information of the LIHC cohort were obtained from The Cancer Genome Atlas. Differentially expressed genes were found using the R package "limma". Subsequently, a prognostic gene signature was developed using the LASSO Cox regression model. Kaplan-Meier, log-rank, and receiver operating characteristic (ROC) analyses were performed to verify the predictive accuracy of the prognostic model. Finally, a nomogram and calibration plot were created using the "rms" package. Differentially expressed genes were screened with threshold criteria (FDR < 0.01 and |log FC|>3) and 563 differentially expressed genes were obtained, including 448 downregulated and 115 upregulated genes. Using the LASSO Cox regression model, a prognostic gene signature was developed based on nine genes, IQGAP3, BIRC5, PTTG1, STC2, CDKN3, PBK, EXO1, NEIL3, and HOXD9, the expression levels of which were quantitated using RT-qPCR. According to the risk scores, patients were separated into high-risk and low-risk groups. In conclusion, the prognostic gene signature can be used as a combined biomarker for the independent prediction of overall survival in HCC patients. Moreover, we created a nomogram that can be used to infer prognosis and aid individualized decisions regarding treatment and surveillance.
Collapse
Affiliation(s)
- Cuiyun Wu
- Department of Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China
| | - Yaosheng Luo
- Medical research center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China
| | - Yinghui Chen
- Department of Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China
| | - Hongling Qu
- Department of Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China
| | - Lin Zheng
- Department of Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China
| | - Jie Yao
- Department of Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China; Medical research center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China.
| |
Collapse
|
|
33
|
Mack PC, Klein MI, Ayers KL, Zhou X, Guin S, Fink M, Rossi M, AI-Kateb H, O’Connell T, Hantash FM, Oh WK, Newman S, Schadt EE, Chen R, Hirsch FR. OUP accepted manuscript. Oncologist 2022; 27:476-486. [PMID: 35298662 PMCID: PMC9177106 DOI: 10.1093/oncolo/oyac035] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/16/2022] [Indexed: 11/14/2022] Open
Abstract
Introduction Methods Results Conclusion
Collapse
Affiliation(s)
- Philip C Mack
- Corresponding author: Philip C. Mack, Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Health System, One Gustave L. Levy Place, New York, NY 10029, USA. Tel: 212 241-0776;
| | | | | | | | | | | | | | | | | | - Feras M Hantash
- Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA
- Sema4, Stamford, CT, USA
| | - William K Oh
- Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA
- Sema4, Stamford, CT, USA
| | | | | | | | | |
Collapse
|
|
34
|
Zazzara M, Nazaraj A, Scarcia M, Cardo G, Carando R, Ludovico GM. Electromotive Drug Administration of Mitomycin C (EMDA/MMC) versus Intravesical Immunotherapy with Bacillus Calmette-Guérin (BCG) in Intermediate and High Risk Non Muscle Invasive Bladder Cancer. Urol Int 2021; 107:64-71. [PMID: 34933307 DOI: 10.1159/000520630] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/24/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Although TURB of tumor (TURBT) by itself can eradicate a non-muscle-invasive bladder cancer (NMIBC) completely, these tumors commonly recur and can progress to MIBC. It is, therefore, necessary to consider adjuvant therapy in most patients. The primary objective of the present study was to report our experience with EMDA/MMC and BCG, considering efficacy, progression, and recurrence, as adjuvant therapy in NMIBC patients; the secondary objective was to assess the efficacy of EMDA/MMC versus BCG as a comparative treatment. METHODS Between April 2016 and February 2020, a series of 216 patients, with a diagnosis of intermediate- and high-risk NMIBC after TURBT, underwent adjuvant intravesical therapy. In 26 cases with a failure of the treatment, in patients unfit and unwilling for radical cystectomy, a repeated intravesical therapy was performed (2 had a twice repetition). Out of 244 adjuvant therapies, 140 EMDA/MMC and 104 BCG treatments were done. The following data were collected for each patient: baseline demographics and clinical data and perioperative and postoperative data. Overall patients' adjuvant intravesical therapies were included in a prospectively maintained institutional database, and a retrospective chart review was performed. We collected data on 2 main outcomes, recurrence-free survival (defined as a negative cystoscopy, cytology, and/or histology at the evaluation time point) and progression-free survival (defined as a negative cystoscopy or a nonprogressive tumor recurrence). RESULTS The NMIBC progression rate was higher in BCG than EMDA/MMC but not statistically significant (respectively, 4.2% vs. 2.5%; p = 0.703). In the overall population, the risk of NMIBC recurrence was higher after BCG than EMDA/MMC (p = 0.025). In the subgroups of 59 paired patients with similar characteristics, no difference was observed between groups in NMIBC progression and recurrence. CONCLUSIONS Our findings suggest that EMDA/MMC and BCG are safe and reproducible approaches as adjuvant treatment in NMIBC. EMDA/MMC permits to achieve a fine oncological management as adjuvant treatment in NMIBC, which is not less than that obtained with BCG.
Collapse
Affiliation(s)
- Michele Zazzara
- Department of Urology, Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, Italy
| | - Arjan Nazaraj
- Department of Urology, Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, Italy
| | - Marcello Scarcia
- Department of Urology, Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, Italy
| | - Giuseppe Cardo
- Department of Urology, Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, Italy
| | - Roberto Carando
- Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland.,Clinica Luganese Moncucco, Lugano, Switzerland.,Clinica S. Anna, Sorengo, Switzerland.,Clinica S. Chiara, Locarno, Switzerland
| | - Giuseppe Mario Ludovico
- Department of Urology, Ente Ecclesiastico Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, Italy
| |
Collapse
|
|
35
|
Abdulla MH, Shaik AS, Vaali-Mohammed MA, Al Khayal KA, Traiki TB, Zubaidi AM, Al-Johani T, Shakoor Z, Al-Obeed OA. Expression of VEGF, EGF and HGF in early- and late-stage colorectal cancer. Mol Clin Oncol 2021; 15:251. [PMID: 34671470 DOI: 10.3892/mco.2021.2413] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 03/17/2021] [Indexed: 01/24/2023] Open
Abstract
The heterogenous nature of colorectal cancer (CRC) highlights the need for a better understanding of the growth factors that affect tumour growth and cancer progression. The aim of the present study was to evaluate the role of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the early (I and II) and late (III and IV) stages of CRC. The serum levels and mRNA expression (n=30) of the aforementioned growth factors were measured and immunohistochemistry (n=20) was performed in patients with CRC. Histological examination revealed comparable distribution of early-stage [I: 8 (26.7%) and II: 7 (23.3%)] and late-stage [III: 8 (26.7%) and IV: 7 (23.3%)] CRC. The mean serum concentrations of VEGF during the early (152.9±14.5 vs. 88.39±3.99 pg/ml; P=0.001) and late (182.7±25.8 vs. 88.39±3.99 pg/ml; P=0.002) stages were significantly higher compared with those in controls. Similarly, the mean serum concentrations of EGF in the early (409.4±7.96 vs. 153.7±13.8 pg/ml; P=0.05) and HGF in the late (90.4±17.4 vs. 56.9±4.97 pg/ml; P=0.05) stages were significantly higher compared with those in controls. The serum concentrations of VEGF, EGF and HGF were comparable between the early and late stages of CRC. Compared to normal tissues, the mRNA expression of both VEGF (P<0.001) and HGF (P<0.01) was upregulated in early-stage and downregulated in late-stage CRC. The expression of EGF remained significantly elevated during both the early and late stages of CRC (P<0.01). Histopathological analyses confirmed increased expression of VEGF in cancerous tissues compared with that in normal tissues. The present study emphasized the need for monitoring the serum levels and tissue expression of growth factors to fully elucidate their role in patients with CRC.
Collapse
Affiliation(s)
- Maha-Hamadien Abdulla
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| | - Asma Sultana Shaik
- Prince Naif Health Research Centre, King Saud University, Riyadh 11472, Saudi Arabia
| | - Mansoor-Ali Vaali-Mohammed
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| | - Khayal Abdulmalik Al Khayal
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| | - Thamer Bin Traiki
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| | - Ahmad Mohammed Zubaidi
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| | - Tariq Al-Johani
- Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University Medical City, Riyadh 11472, Saudi Arabia
| | - Zahid Shakoor
- Department of Immunology, King Saud University Medical City, Riyadh 11472, Saudi Arabia
| | - Omar Abdullah Al-Obeed
- Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia
| |
Collapse
|
|
36
|
Hentrich MU, Bower M, Daugaard G, Dieing A, Bickel M, Berretta M, Lesmeister F, Jurinovic V, Stoehr A, Heinzelbecker J, Krznaric I, Dieckmann KP, Necchi A, Maroto Rey P, Rockstroh JK, Brito M, Pfister D, Hoffmann C. Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study. Cancer 2021; 128:260-268. [PMID: 34592009 DOI: 10.1002/cncr.33928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 08/08/2021] [Accepted: 08/09/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.
Collapse
Affiliation(s)
- Marcus Ulrich Hentrich
- Department of Hematology and Oncology, Red Cross Hospital, University of Munich, Munich, Germany
| | - Mark Bower
- National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, United Kingdom
| | - Gedske Daugaard
- Department of Oncology, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark
| | - Annette Dieing
- Department of Hematology and Oncology, Vivantes Klinikum am Urban, Berlin, Germany
| | | | - Massimiliano Berretta
- National Cancer Institute, Aviano, Italy.,Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Florian Lesmeister
- Department of Hematology and Oncology, Red Cross Hospital, University of Munich, Munich, Germany
| | - Vindi Jurinovic
- Institute of Biometrics and Epidemiology, Ludwig Maximilian University of Munich, Munich, Germany
| | | | - Julia Heinzelbecker
- Department of Urology and Pediatric Urology, Saarland University Medical Center and Saarland University, Homburg, Germany
| | | | | | - Andrea Necchi
- IRCCS San Raffaele Hospital and Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Pablo Maroto Rey
- Department of Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Margarida Brito
- Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal
| | - David Pfister
- Department of Urology, University Hospital Cologne, Cologne, Germany
| | - Christian Hoffmann
- ICH Study Center, Hamburg, Germany.,University Hospital of Schleswig Holstein, Kiel, Germany
| |
Collapse
|
|
37
|
Weiss BG, Anczykowski MZ, Ihler F, Bertlich M, Spiegel JL, Haubner F, Canis M, Küffer S, Hess J, Unger K, Kitz J, Jakob M. MicroRNA-182-5p and microRNA-205-5p as potential biomarkers for prognostic stratification of p16-positive oropharyngeal squamous cell carcinoma. Cancer Biomark 2021; 33:331-347. [PMID: 34542062 DOI: 10.3233/cbm-203149] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND MicroRNAs constitute promising biomarkers. OBJECTIVE The aim was to investigate diagnostic and prognostic implications of miR-182-5p and miR-205-5p in p16-positive and p16-negative oropharyngeal squamous cell carcinomas (OPSCCs). METHODS Expression of miR-182-5p, miR-205-5p were determined via quantitative real-time-PCR in fresh frozen tissues of 26 p16-positive, 19 p16-negative OPSCCs and 18 HPV-negative oropharyngeal controls. Associations between miRNA-expression, clinicopathological characteristics and prognosis were analyzed. RESULTS Higher miR-182-5p expression was associated with significant inferior disease-specific survival for p16-positive OPSCCs (HR = 1.98E+09, 95% CI 0-Inf; P= 0.028) and a similar trend was observed for p16-negative OPSCCs (HR = 1.56E+09, 95% CI 0-Inf; P= 0.051). Higher miR-205-5p expression was associated with an inferior progression-free survival (HR = 4.62, 95% CI 0.98-21.83; P= 0.034) and local control rate (HR = 2.18E+09, 95% CI 0-Inf; P= 0.048) for p16-positive OPSCCs. CONCLUSIONS Results indicate that miR-182-5p and miR-205-5p can further stratify patients with p16-positive OPSCC into prognostic groups.
Collapse
Affiliation(s)
- Bernhard G Weiss
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany.,Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Mahalia Zoe Anczykowski
- Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Göttingen, Germany.,Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Friedrich Ihler
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany.,German Center for Vertigo and Balance Disorders (DSGZ), Ludwig-Maximilians University of Munich, Munich, Germany
| | - Mattis Bertlich
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Jennifer L Spiegel
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Frank Haubner
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Martin Canis
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Stefan Küffer
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Julia Hess
- Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany.,Department of Radiation Oncology, University Hospital, LMU Munich, Germany.,Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany
| | - Kristian Unger
- Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany.,Department of Radiation Oncology, University Hospital, LMU Munich, Germany.,Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Munich, Germany
| | - Julia Kitz
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.,Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| | - Mark Jakob
- Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany.,Department of Otorhinolaryngology, Ludwig-Maximilians University of Munich, Munich, Germany
| |
Collapse
|
|
38
|
Takagi T, Yoshida K, Kondo T, Fukuda H, Ishihara H, Kobayashi H, Iizuka J, Ishida H, Tanabe K. Hypopituitarism in patients with metastatic renal cell carcinoma treated with ipilimumab and nivolumab combination therapy. Jpn J Clin Oncol 2021; 51:1744-1750. [PMID: 34487184 DOI: 10.1093/jjco/hyab141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 08/21/2021] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE We investigated the incidence of hypopituitarism in Japanese patients with metastatic renal cell carcinoma (mRCC) who received ipilimumab and nivolumab (I-P) therapy and compared patient characteristics and survival rates between patients with hypopituitarism and those without. METHODS Twenty-two patients with mRCC who received I-P therapy as first-line treatment were the subjects of this retrospective study. The diagnosis of hypopituitarism was based on the hormone loading test. RESULTS Hypopituitarism occurred in 41% (9/22) patients who received I-P therapy. Median time of diagnosis was 12 weeks (IQR: 9.5-20). Clinical symptoms, such as fatigue, weakness or fever, were observed in 7 patients, while 2 patients had no clinical presentation. The following deficiency patterns were observed: isolated ACTH in 4 patients, ACTH and GH in 2 patients, ACTH and TSH in 2 patients and triple deficiency (ACTH, GH and TSH) in 1 patient. All patients with hypopituitarism were in the IMDC intermediate group, while 46% of those without hypopituitarism were in the IMDC intermediate group. Other patient characteristics were not different between the two groups. Object response rate was 33% (3/9) in patients with hypopituitarism and 23% (3/13) in those without (P = 0.5954). Progression free survival (PFS) was significantly longer in those with hypopituitarism than those without (median: 24.7 vs. 4.5 months, P = 0.0008), while overall survival did not differ (P = 0.136). CONCLUSIONS Compared with the clinical trial, the incidence of hypopituitarism was higher than expected. Patients with hypopituitarism tended to have longer PFS, which may suggest that optimal management of hypopituitarism results in better prognosis.
Collapse
Affiliation(s)
- Toshio Takagi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazuhiko Yoshida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Tsunenori Kondo
- Department of Urology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Hironori Fukuda
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroki Ishihara
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | | | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ishida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| |
Collapse
|
|
39
|
Takahashi K, Nishikawa K, Tanishima Y, Ishikawa Y, Masuda T, Kurogochi T, Yuda M, Tanaka Y, Matsumoto A, Yano F, Eto K. Risk stratification of anastomotic leakage using eGFR and FIB-4 index in patients undergoing esophageal cancer surgery. Langenbecks Arch Surg 2021; 406:1867-1874. [PMID: 34313831 DOI: 10.1007/s00423-021-02272-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Renal insufficiency and liver cirrhosis are identified as independent risk factors for anastomotic leakage (AL) after esophagectomy. However, research evaluating the incidence of AL using quantitative data to measure renal function and liver fibrosis remain to be limited. Therefore, this study was conducted to evaluate postoperative AL after esophagectomy using estimated glomerular filtration rate (eGFR) and fibrosis-4 (FIB-4) index. METHODS In total, 184 patients who underwent esophagectomy were included in this study; then, they were divided into the non-AL group (n = 161) and AL group (n = 23), after which their background data and intraoperative and postoperative outcomes were compared. In addition, risk factors for AL were evaluated using a logistic regression model. RESULTS Preoperative body mass index of ≥21.5 kg/m2, hemoglobin A1c level of ≥7.3%, FIB-4 index of ≥1.44, and eGFR of <59 ml/min/1.73 m2 were found to be significantly frequent in the AL group compared with the non-AL group. Multivariate analysis revealed FIB-4 index of ≥1.44 (p = 0.013; OR, 3.780; 95% CI, 1.320-10.800) and eGFR of <59 ml/min/1.73 m2 (p = 0.018; OR, 3.110; 95% CI, 1.220-8.020) as the independent risk factors for AL. In addition, we stratified the patients into three groups based on the incidence of AL as follows: low risk (5.5%, low FIB-4 index), intermediate risk (13.0%, high FIB-4 index and eGFR), and high risk (37.5%, high FIB-4 index and low eGFR). CONCLUSION Preoperative eGFR and FIB-4 index were found to be useful markers to predict AL after esophagectomy.
Collapse
Affiliation(s)
- Keita Takahashi
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Katsunori Nishikawa
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuichiro Tanishima
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoshitaka Ishikawa
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takahiro Masuda
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takanori Kurogochi
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masami Yuda
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yujiro Tanaka
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Akira Matsumoto
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Fumiaki Yano
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Ken Eto
- Department of Gastrointestinal Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| |
Collapse
|
|
40
|
Comparison of the outcomes between total eversion and conventional triangulating stapling technique in cervical esophagogastric anastomosis after esophagectomy: a propensity score-matched analysis. Esophagus 2021; 18:475-481. [PMID: 33523356 DOI: 10.1007/s10388-021-00816-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/15/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Anastomotic leakage and stenosis remain major problems after esophageal reconstruction. This study evaluated the clinical outcomes between the total eversion (TE) triangulating stapling technique (TST) and conventional (C) TST. METHODS The study included 404 consecutive patients with esophageal cancer who underwent cervical esophagogastrostomy by TST between January 2013 and December 2018. The postoperative outcomes were compared between TE-TST and C-TST using propensity score-matched analysis. RESULTS Before matching, the cT stage and the cTNM stage were different between the groups. After matching, each group consisted of 128 patients. The patients' background characteristics were similar between the groups. Although the incidence of anastomotic leakage was similar between the groups (p = 0.216), anastomotic stricture occurred in 19 (14.8%) and 7 (5.5%) patients in the C-TST and the TE-TST groups, respectively (p = 0.021). CONCLUSIONS The incidence of anastomotic stenosis was significantly lower in the TE-TST group than in the C-TST group. TE-TST decreases the incidence of anastomotic stricture and can improve the quality of life in patients undergoing esophagectomy.
Collapse
|
|
41
|
Shi B, Hu X, He H, Fang W. Metformin suppresses breast cancer growth via inhibition of cyclooxygenase‑2. Oncol Lett 2021; 22:615. [DOI: https:/doi.org/10.3892/ol.2021.12876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025] Open
Affiliation(s)
- Bin Shi
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| | - Xinyu Hu
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| | - Huimin He
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| | - Wenzheng Fang
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| |
Collapse
|
|
42
|
Shi B, Hu X, He H, Fang W. Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2. Oncol Lett 2021; 22:615. [PMID: 34257723 PMCID: PMC8243079 DOI: 10.3892/ol.2021.12876] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 05/26/2021] [Indexed: 12/13/2022] Open
Abstract
Pre-clinical and on-going trials have indicated the advantage of using metformin as an anticancer drug alone or in combination with other chemotherapeutics for the treatment of patients with breast cancer. However, the mechanisms by which metformin attenuates tumorigenesis remain to be further elucidated. The present study investigated the anticancer effects of metformin in breast cancer and identified potential molecular targets of metformin using western blotting and immunohistochemical analysis. Metformin significantly decreased tumor cell proliferation in vitro and suppressed tumor growth in vivo. Moreover, it induced the activation of AMP-induced protein kinase and suppression of phosphorylated-eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1), a downstream effector of the mTOR signaling pathway, and decreased cyclin D1 levels in in vitro and in vivo experimental models. Additionally, metformin inhibited cyclooxygenase (COX)-2 expression. Clinically, high expression levels of COX-2 and p-4E-BP1 in tissues of patients with breast cancer were significantly associated with enhanced lymphatic metastasis and distant metastasis. Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways.
Collapse
Affiliation(s)
- Bin Shi
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China.,Department of Medical Oncology, Longyan People's Hospital, Longyan, Fujian 364000, P.R. China
| | - Xinyu Hu
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| | - Huimin He
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| | - Wenzheng Fang
- Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
| |
Collapse
|
|
43
|
Takahashi K, Nishikawa K, Furukawa K, Tanishima Y, Ishikawa Y, Kurogochi T, Yuda M, Tanaka Y, Matsumoto A, Mitsumori N, Ikegami T. Prognostic Significance of Preoperative Osteopenia in Patients Undergoing Esophagectomy for Esophageal Cancer. World J Surg 2021; 45:3119-3128. [PMID: 34152448 DOI: 10.1007/s00268-021-06199-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Osteopenia, which exhibits low bone mineral density (BMD), has been linked to sarcopenia and recently reported as a prognostic factor in various cancers. However, the prognostic significance of osteopenia in esophageal cancer remains unclear. Hence, this study aimed to clarify the impact of osteopenia on the prognosis of patients undergoing esophagectomy for esophageal cancer. METHODS We included 229 patients who underwent esophagectomy. BMD was calculated as the average pixel density (Hounsfield unit) within a circle in midvertebral core at the 11th thoracic vertebra on preoperative computed tomography. We then divided the patients into the Osteopenia group (n = 159) and the Non-Osteopenia group (n = 70) according to the optimal cutoff value obtained from the receiver operating characteristic curve. Their clinicopathological data, prognosis, and recurrence were analyzed. RESULTS The mean age was significantly older in the Osteopenia group (p = 0.047). The Osteopenia group had significantly worse overall survival (OS) and relapse-free survival (RFS) than the Non-Osteopenia group (p = 0.001 and p = 0.012, respectively). Multivariate analysis revealed osteopenia was an independent prognostic factor for OS (p < 0.001; hazard ratio [HR], 2.243; 95% confidence interval [CI], 1.422-3.538) and RFS (p = 0.008; HR, 1.739; 95% CI, 1.154-2.620). In logistic regression model, advanced age and cStage III-IV were independent risk factors for preoperative osteopenia. CONCLUSIONS Preoperative osteopenia is associated with poor survival and recurrence in patients undergoing esophagectomy for esophageal cancer.
Collapse
Affiliation(s)
- Keita Takahashi
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Katsunori Nishikawa
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kenei Furukawa
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuichiro Tanishima
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoshitaka Ishikawa
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takanori Kurogochi
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masami Yuda
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yujiro Tanaka
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Akira Matsumoto
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Norio Mitsumori
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Toru Ikegami
- Department of Gastroenterological Surgery, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan
| |
Collapse
|
|
44
|
Suzuki K, Hara T, Terakawa T, Furukawa J, Harada K, Hinata N, Nakano Y, Fujisawa M. The Efficacy of Surgical Metastasectomy for Solitary Metastasis of Renal Cell Carcinoma. Urol Int 2021; 106:397-403. [PMID: 34134119 DOI: 10.1159/000516679] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/16/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND Patients with solitary metastasis of renal cell carcinoma (RCC) have shown to be ideal candidates for surgical metastasectomy (SM). However, whether SM will show more benefit than systemic therapy remains unclear. METHODS We included 73 patients treated for solitary metastasis after nephrectomy at our institute from April 2008 to December 2018. We compared the clinical outcomes between the SM (n = 29) and no-SM (n = 44) group which were treated with only systemic therapy. RESULTS Eleven of 29 patients in the SM group received presurgical targeted therapy (PTT). Although 13 of 29 patients in the SM group showed recurrence during the study period, a Cox proportional hazards model showed that SM was significantly associated with a favorable overall survival (hazard ratio: 0.18; p = 0.007). Patients receiving PTT prior to SM showed a longer recurrence-free survival after SM in comparison to those who underwent SM without PTT (median: not reached vs. 27.7 months; p = 0.009). CONCLUSIONS If resection is feasible, SM may be beneficial for patients with solitary metastasis of RCC, and we showed the possibility that PTT prior to SM may be effective for avoiding recurrence after SM. Further large-scale prospective studies are needed to clarify the ideal treatment strategy for metastatic RCC.
Collapse
Affiliation(s)
- Kotaro Suzuki
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takuto Hara
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoaki Terakawa
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Junya Furukawa
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Harada
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Nobuyuki Hinata
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuzo Nakano
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masato Fujisawa
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| |
Collapse
|
|
45
|
Cao X, Cui J, Li Z, Zhao G. Preoperative C-Reactive Protein/Albumin Ratio is a Prognostic Indicator for Survival in Surgically Treated Gastrointestinal Stromal Tumors: A Retrospective Cohort Study. Cancer Manag Res 2021; 13:4155-4167. [PMID: 34079369 PMCID: PMC8163582 DOI: 10.2147/cmar.s307873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/10/2021] [Indexed: 11/23/2022] Open
Abstract
Background Systemic inflammation and malnutrition may promote tumor progression. C-reactive protein/albumin ratio (CAR) is linked to the poor long-term survival of several malignant tumors. Purpose To explore the predictive value of CAR in gastrointestinal stromal tumors (GISTs). Methods A retrospective study was conducted on 325 patients with primary GIST surgically treated with curative intent from 2009 to 2018. The cut-off point of CAR was set using X-tile software. Kaplan–Meier method and multivariate Cox regression model were used to study the prognostic value of CAR. The time-dependent receiver operating characteristic curve (tROC) was drawn, and the prognostic accuracy of CAR, Glasgow prognostic score (GPS), and National Institute of Health (NIH) risk classification was compared by the area under the curve (AUC). Results The best cut-off point of CAR was 0.55. Increased CAR was associated with the location of the lower digestive tract, larger tumor size, higher mitotic index, higher NIH risk classification, lower ALB, higher CRP, and higher GPS (all p<0.05). Multivariable analysis revealed that CAR (hazard ratio [HR] 2.598, 95% confidence interval [CI] 1.385–4.874; p=0.003) was an independent predictor of overall survival. Additionally, the AUC of CAR was lower than that of NIH risk classification at 2 years (0.601 vs. 0.775, p=0.002) and 5 years (0.629 vs 0.735, p=0.069). However, the AUC of NIH risk classification significantly increased (2-year OS 0.801, p=0.251; 5-year OS 0.777, p=0.011) when combined with CAR. Conclusion CAR is a new independent predictor of poor survival in patients with GIST. CAR combined with NIH risk classification can effectively improve the performance of prognosis prediction.
Collapse
Affiliation(s)
- Xianglong Cao
- Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jian Cui
- Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Zijian Li
- Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| |
Collapse
|
|
46
|
Comment on "Circulating Tumor Cells-New Indicator For Clinical Staging Of Patients With Esophageal Cancer". Ann Surg 2021; 274:e913-e914. [PMID: 34029224 DOI: 10.1097/sla.0000000000004948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
47
|
Abrahamsson H, Meltzer S, Hagen VN, Johansen C, Bousquet PA, Redalen KR, Ree AH. Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer. BMC Cancer 2021; 21:535. [PMID: 33975557 PMCID: PMC8111928 DOI: 10.1186/s12885-021-08260-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/27/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients. METHODS Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013-2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival. RESULTS In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex. CONCLUSION This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women. TRIAL REGISTRATION ClinicalTrials.gov NCT01816607 ; registration date: 22 March 2013.
Collapse
Affiliation(s)
- Hanna Abrahamsson
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Sebastian Meltzer
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Vidar Nyløkken Hagen
- Department of Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway
| | - Christin Johansen
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Paula A Bousquet
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Kathrine Røe Redalen
- Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway
| | - Anne Hansen Ree
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway. .,Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| |
Collapse
|
|
48
|
Santiago L, Castro M, Sanz-Pamplona R, Garzón M, Ramirez-Labrada A, Tapia E, Moreno V, Layunta E, Gil-Gómez G, Garrido M, Peña R, Lanuza PM, Comas L, Jaime-Sanchez P, Uranga-Murillo I, Del Campo R, Pelegrín P, Camerer E, Martínez-Lostao L, Muñoz G, Uranga JA, Alcalde A, Galvez EM, Ferrandez A, Bird PI, Metkar S, Arias MA, Pardo J. Extracellular Granzyme A Promotes Colorectal Cancer Development by Enhancing Gut Inflammation. Cell Rep 2021; 32:107847. [PMID: 32640217 DOI: 10.1016/j.celrep.2020.107847] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 02/11/2020] [Accepted: 06/11/2020] [Indexed: 02/06/2023] Open
Abstract
If not properly regulated, the inflammatory immune response can promote carcinogenesis, as evident in colorectal cancer (CRC). Aiming to gain mechanistic insight into the link between inflammation and CRC, we perform transcriptomics analysis of human CRC, identifying a strong correlation between expression of the serine protease granzyme A (GzmA) and inflammation. In a dextran sodium sulfate and azoxymethane (DSS/AOM) mouse model, deficiency and pharmacological inhibition of extracellular GzmA both attenuate gut inflammation and prevent CRC development, including the initial steps of cell transformation and epithelial-to-mesenchymal transition. Mechanistically, extracellular GzmA induces NF-κB-dependent IL-6 production in macrophages, which in turn promotes STAT3 activation in cultured CRC cells. Accordingly, colon tissues from DSS/AOM-treated, GzmA-deficient animals present reduced levels of pSTAT3. By identifying GzmA as a proinflammatory protease that promotes CRC development, these findings provide information on mechanisms that link immune cell infiltration to cancer progression and present GzmA as a therapeutic target for CRC.
Collapse
Affiliation(s)
- Llipsy Santiago
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Marta Castro
- Department of Pharmacology and Physiology, Faculty of Health and Sports Sciences, University of Zaragoza, 22002 Huesca, Spain
| | - Rebeca Sanz-Pamplona
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Marcela Garzón
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Ariel Ramirez-Labrada
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Elena Tapia
- Animal Unit, University of Zaragoza, 50009 Zaragoza, Spain
| | - Víctor Moreno
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Elena Layunta
- Department of Pharmacology and Physiology, Faculty of Veterinary, University of Zaragoza, 50013 Zaragoza, Spain
| | - Gabriel Gil-Gómez
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona
| | - Marta Garrido
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona
| | - Raúl Peña
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona
| | - Pilar M Lanuza
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Laura Comas
- Instituto de Carboquímica ICB-CSIC, 50018 Zaragoza, Spain
| | - Paula Jaime-Sanchez
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Iratxe Uranga-Murillo
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain
| | - Rosa Del Campo
- Department of Microbiology, University Hospital Ramón y Cajal & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
| | - Pablo Pelegrín
- Unidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Eric Camerer
- Université de Paris, Paris Cardiovascular Research Center, INSERM U970, 75015 Paris, France
| | - Luis Martínez-Lostao
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; Department of Immunology, University Clinic Hospital Lozano Blesa, 50009, Zaragoza, Spain and Department of Pathology, University Clinic Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBEREHD, 50009 Zaragoza, Spain; Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain; Department Biochemistry and Molecular and Cell Biology and Department Microbiology, Preventive Medicine and Public Health, University of Zaragoza, 50009 Zaragoza, Spain
| | - Guillermo Muñoz
- Department of Immunology, University Clinic Hospital Lozano Blesa, 50009, Zaragoza, Spain and Department of Pathology, University Clinic Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBEREHD, 50009 Zaragoza, Spain
| | - José A Uranga
- Department of Basis Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain
| | - Anabel Alcalde
- Department of Pharmacology and Physiology, Faculty of Veterinary, University of Zaragoza, 50013 Zaragoza, Spain
| | - Eva M Galvez
- Instituto de Carboquímica ICB-CSIC, 50018 Zaragoza, Spain
| | - Angel Ferrandez
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, Spain
| | - Phillip I Bird
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University 3800 Melbourne, Australia
| | | | - Maykel A Arias
- Instituto de Carboquímica ICB-CSIC, 50018 Zaragoza, Spain.
| | - Julian Pardo
- Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; Aragon I+D Foundation (ARAID), Zaragoza, Spain; Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain; Department Biochemistry and Molecular and Cell Biology and Department Microbiology, Preventive Medicine and Public Health, University of Zaragoza, 50009 Zaragoza, Spain; CIBER-BBN, Madrid, Spain.
| |
Collapse
|
|
49
|
Fang X, Bai Y, Zhang L, Ding S. MicroRNA-665 regulates the proliferation, apoptosis and adhesion of gastric cancer cells by binding to cadherin 3. Oncol Lett 2021; 21:494. [PMID: 33968210 PMCID: PMC8100969 DOI: 10.3892/ol.2021.12755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 03/23/2021] [Indexed: 12/15/2022] Open
Abstract
Numerous studies have reported that abnormal cadherin 3 (CDH3) and microRNA (miRNA/miR)-665 expression can induce the progression of gastric cancer (GC). However, the mechanism of interaction between miR-665 and CDH3 in GC requires further investigation. The present study aimed to investigate the influence of miR-665 and CDH3 in GC development. The effect of miR-665 and CDH3 on GC tissues and cell lines was examined using reverse transcription-quantitative PCR. Subsequently, CDH3 protein expression in GC cell lines was detected using western blotting. To confirm the association between miR-665 and CDH3, a dual-luciferase reporter assay system was employed. Cell proliferation and adhesion were analyzed using BrdU ELISA, MTT and cell adhesion assays. Finally, caspase-3 activity assay kit and FITC apoptosis detection kit were used for the determination of apoptosis of GC cells. The current findings confirmed the upregulation of CDH3 expression in GC cell lines and tissues. Experimental results indicated that CDH3 overexpression increased cell proliferation and adhesion, but decreased the apoptosis level of the cells. Similarly, the miR-665 inhibitor enhanced cell proliferation and adhesion, but inhibited apoptosis of GC cells. Additionally, it was observed that CDH3 was a direct target of miR-665 in GC cells and that miR-665 inhibited CDH3 expression, thereby repressing the progression of GC. In conclusion, the present study suggested that by targeting CDH3, miR-665 suppressed the progression of GC. These findings may provide a significant theoretical basis for future GC clinical therapy.
Collapse
Affiliation(s)
- Xinhui Fang
- Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, P.R. China
| | - Yangqiu Bai
- Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, P.R. China
| | - Lida Zhang
- Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, P.R. China
| | - Songze Ding
- Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, P.R. China
| |
Collapse
|
|
50
|
Zhang Q, Liang J, Chen J, Mei S, Wang Z. Outcomes of Laparoscopic Versus Open Surgery in Elderly Patients with Rectal Cancer. Asian Pac J Cancer Prev 2021; 22:1325-1329. [PMID: 33906329 PMCID: PMC8325135 DOI: 10.31557/apjcp.2021.22.4.1325] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Laparoscopic colorectal resection has been gaining popularity over the past two decades-and the number of elderly patients with colorectal cancer treated with a surgical modality has gradually increased. However, studies about laparoscopic rectal surgery in elderly patients with long-term oncologic outcomes are limited. In this study, we evaluated the safety and effectiveness of laparoscopic resection in patients with rectal cancer aged ≥80 y. Methods: From 2007-2015, a total of 84 consecutive patients with rectal cancer from a single institution were included, 45 patients undergoing laparoscopic rectal resection were compared with 39 patients undergoing open rectal resection. Results: The two groups were well balanced in terms of age, gender, body mass index, American society of anesthesiologists scores, previous abdominal surgery, neoadjuvant therapy, tumor stage, distance of tumor from the anal verge, and comorbidities. One (2.2%) patient in the laparoscopic group required conversion to open surgery. Laparoscopic surgery was associated with significantly longer operating time (160.1±28.2 versus 148.2±41.3 min; P=0.031), less intraoperative blood loss (80.5±20.9 versus 160.3±42.4 mL; P=0.002), less need of blood transfusion (6.7% versus 20.5%; P=0.003), a shorter time to diet recovery (2.5±1.5 versus 4.9±1.1; P=0.015) and postoperative hospital stay (7.5±4.5 versus 10.8±4.2; P=0.035), lower overall postoperative complication rate (8.9% versus 20.5%; P=0.017), and wound-related complication rate (4.4% versus 10.2%; P=0.013) when compared with open surgery. Specimen length, no. of retrieced lymph nodes, positive distal and circumferential margin rate, mortality rate, and reoperation rate were not significantly different between two groups. The disease-free and overall 5-year survival rates were similar between two groups. Conclusions: Laparoscopic rectal surgery is safe and feasible in patients aged≥80 y and is associated with similar long-term oncologic outcomes when compared with open surgery.
Collapse
Affiliation(s)
- Qi Zhang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Jianwei Liang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Jianan Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Shiwen Mei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Zheng Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| |
Collapse
|