|
1
|
Lu JL, Cheng Y, Xu ZL, Qian GX, Wei MT, Jia WD. Immune checkpoint inhibitors plus anti-angiogenesis in patients with resected high-risk hepatitis B virus-associated hepatocellular carcinoma. World J Gastrointest Oncol 2025; 17:101371. [DOI: 10.4251/wjgo.v17.i4.101371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 01/25/2025] [Accepted: 02/13/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Currently, there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) after radical resection. Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC, we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.
AIM To evaluate the value of postoperative combined therapy (PCT) with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.
METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included. Recurrence-free survival (RFS) and overall survival were assessed using propensity score matching and inverse probability of treatment weighting. Cox regression analysis was used to identify factors affecting recurrence, and subgroup analysis was conducted to investigate the impact of medications on different populations. Treatment-related adverse events and liver function measurements were evaluated.
RESULTS A total of 150 patients were recruited, of whom 30 underwent PCT and 120 did not. After adjusting for confounders, patients who underwent PCT had better RFS at 6 and 12 months than those who did not (P > 0.05). Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting, although the difference was not statistically significant (P > 0.05). A maximum diameter of > 5 cm, vascular invasion, satellite nodules, and high gamma-glutamyl transferase levels were independent risk factors for recurrence (P < 0.05). No significant interaction effects were observed in subgroup analyses. The most prevalent adverse event was hypertension (66.7%). PCT was associated with an increased risk of hepatic impairment which may predict RFS rates (P = 0.041).
CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT. Hepatic impairment during treatment may indicate recurrence, and close monitoring of liver function and HBV infection is recommended.
Collapse
Affiliation(s)
- Jian-Lin Lu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Yuan Cheng
- Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Zi-Ling Xu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Gui-Xiang Qian
- Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ming-Tong Wei
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Wei-Dong Jia
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| |
Collapse
|
|
2
|
Tanemura A, Noguchi D, Shinkai T, Ito T, Hayasaki A, Gyoten K, Fujii T, Iizawa Y, Murata Y, Kuriyama N, Kishiwada M, Mizuno S. Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma. BMC Surg 2024; 24:339. [PMID: 39468556 PMCID: PMC11520444 DOI: 10.1186/s12893-024-02642-6] [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: 01/10/2024] [Accepted: 10/21/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy. METHODS Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis. RESULTS The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001). CONCLUSIONS Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.
Collapse
Affiliation(s)
- Akihiro Tanemura
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan.
| | - Daisuke Noguchi
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Toru Shinkai
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Takahiro Ito
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Aoi Hayasaki
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Kazuyuki Gyoten
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Takehiro Fujii
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Yusuke Iizawa
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Yasuhiro Murata
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Naohisa Kuriyama
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Masashi Kishiwada
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| |
Collapse
|
|
3
|
Hu L, Kong Y, Qiao Y, Wang A. Can adjuvant immune checkpoint inhibitors improve the long-term outcomes of hepatocellular carcinoma with high-risk recurrent factors after liver resection? A meta-analysis and systematic review. Front Oncol 2024; 14:1374262. [PMID: 38854716 PMCID: PMC11162111 DOI: 10.3389/fonc.2024.1374262] [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: 01/21/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024] Open
Abstract
Background Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune checkpoint inhibitors (ICIs) are effective against unresectable HCC; however, their effectiveness and safety for this specific patient group remain uncertain. Methods We conducted an extensive literature search across four scholarly databases to identify relevant studies. Our primary endpoints were overall survival (OS), recurrence-free survival (RFS), and adverse events (AEs). OS and RFS were quantified using hazard ratios (HRs), whereas the 1-, 2-, and 3-year OS and RFS rates were expressed as risk ratios (RRs). Additionally, the incidence of AEs was calculated. Results Our meta-analysis included 11 studies (N = 3,219 patients), comprising two randomized controlled trials (RCTs) and nine retrospective studies. Among these, eight studies reported HRs for OS, showing a statistically significant improvement in OS among patients receiving adjuvant ICIs (HR, 0.60; 95% confidence interval [CI], 0.45-0.80; p < 0.0001). All included studies reported HRs for RFS, indicating a favorable impact of adjuvant ICIs (HR, 0.62; 95% CI, 0.52-0.73; p < 0.0001). Moreover, aggregated data demonstrated improved 1- and 2-year OS and RFS rates with adjuvant ICIs. The incidence rate of AEs of any grade was 0.70 (95% CI, 0.49-0.91), with grade 3 or above AEs occurring at a rate of 0.12 (95% CI, 0.05-0.20). Conclusion Adjuvant ICI therapy can enhance both OS and RFS rates in patients with HCC exhibiting high-risk recurrence factors, with manageable AEs. Systematic review registration https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023488250.
Collapse
Affiliation(s)
- Lingbo Hu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang, China
| | - Yenan Kong
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Yingli Qiao
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Aidong Wang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang, China
| |
Collapse
|
|
4
|
Kim J, Jeong WK, Kim JM, Ha SY, Kim K. Refining MRI-based criteria for portal vein invasion in hepatocellular carcinoma: improving sensitivity beyond portal vein tumor thrombosis. Abdom Radiol (NY) 2024; 49:437-446. [PMID: 37989897 DOI: 10.1007/s00261-023-04106-6] [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: 09/12/2023] [Revised: 10/11/2023] [Accepted: 10/18/2023] [Indexed: 11/23/2023]
Abstract
PURPOSE To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI. METHODS This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics. RESULTS Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p < 0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p = 0.031) with comparable accuracy (95.2% vs. 94.7%; p > 0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p = 0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ = 0.64). CONCLUSION Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.
Collapse
Affiliation(s)
- Jeongju Kim
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Digital Health, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Data Convergence & Future Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
5
|
Abdelsattar S, Fahim SA, Kamel HFM, Al-Amodi H, Kasemy ZA, Khalil FO, Abdallah MS, Bedair HM, Gadallah ANAA, Sabry A, Sakr MA, Selim M, Gayed EMAE. The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma. Noncoding RNA 2023; 9:62. [PMID: 37888208 PMCID: PMC10609931 DOI: 10.3390/ncrna9050062] [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: 08/27/2023] [Revised: 10/04/2023] [Accepted: 10/08/2023] [Indexed: 10/28/2023] Open
Abstract
Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.
Collapse
Affiliation(s)
- Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Sally A. Fahim
- Biochemistry Department, School of Pharmacy, Newgiza University (NGU), Cairo 94114, Egypt;
| | - Hala F. M. Kamel
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Hiba Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Fatma O. Khalil
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mahmoud S. Abdallah
- Clinical Pharmacy Department, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Egypt;
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | | | - Aliaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mohamed A. Sakr
- Medical Microbiology and Immunology Department, Faculty of Medicine, Suez University, Suez 43512, Egypt;
| | - Mahmoud Selim
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31111, Egypt;
| | - Eman M. Abd El Gayed
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| |
Collapse
|
|
6
|
Li J, Wang WQ, Zhu RH, Lv X, Wang JL, Liang BY, Zhang EL, Huang ZY. Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors. Front Immunol 2023; 14:1202039. [PMID: 37359534 PMCID: PMC10285103 DOI: 10.3389/fimmu.2023.1202039] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Background The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs). Methods HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted. Results A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% (P < 0.001) and 54.2% vs. 25.1% (P = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% (P = 0.001) and 84.3% vs. 55.5% (P = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT. Conclusions PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Er-lei Zhang
- *Correspondence: Zhi-yong Huang, ; Er-lei Zhang,
| | | |
Collapse
|
|
7
|
Tanaka S, Noda T, Komeda K, Kosaka H, Iida H, Ueno M, Hokuto D, Ikoma H, Nakai T, Kabata D, Shinkawa H, Kobayashi S, Hirokawa F, Mori H, Hayami S, Morimura R, Matsumoto M, Ishizawa T, Kubo S, Kaibori M. Surgical Outcomes for Hepatocellular Carcinoma in Patients with Child-Pugh Class B: a Retrospective Multicenter Study. J Gastrointest Surg 2023; 27:283-295. [PMID: 36471191 DOI: 10.1007/s11605-022-05549-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/25/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUNDS Liver resection for hepatocellular carcinoma (HCC) in patients with Child-Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection. METHODS Clinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien-Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed. RESULTS Postoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL). CONCLUSION For patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection.
Collapse
Affiliation(s)
- Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan.
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Hisashi Kosaka
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Hiroya Iida
- Division of Gastrointestinal, Breast, and General Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Hisashi Ikoma
- Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Haruki Mori
- Division of Gastrointestinal, Breast, and General Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Ryo Morimura
- Department of Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Masataka Matsumoto
- Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeaki Ishizawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| |
Collapse
|
|
8
|
Chen YD, Zhang L, Zhou ZP, Lin B, Jiang ZJ, Tang C, Dang YW, Xia YW, Song B, Long LL. Radiomics and nomogram of magnetic resonance imaging for preoperative prediction of microvascular invasion in small hepatocellular carcinoma. World J Gastroenterol 2022; 28:4399-4416. [PMID: 36159011 PMCID: PMC9453772 DOI: 10.3748/wjg.v28.i31.4399] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/05/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Microvascular invasion (MVI) of small hepatocellular carcinoma (sHCC) (≤ 3.0 cm) is an independent prognostic factor for poor progression-free and overall survival. Radiomics can help extract imaging information associated with tumor pathophysiology.
AIM To develop and validate radiomics scores and a nomogram of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in sHCC.
METHODS In total, 415 patients were diagnosed with sHCC by postoperative pathology. A total of 221 patients were retrospectively included from our hospital. In addition, we recruited 94 and 100 participants as independent external validation sets from two other hospitals. Radiomics models of Gd-EOB-DTPA-enhanced MRI and diffusion-weighted imaging (DWI) were constructed and validated using machine learning. As presented in the radiomics nomogram, a prediction model was developed using multivariable logistic regression analysis, which included radiomics scores, radiologic features, and clinical features, such as the alpha-fetoprotein (AFP) level. The calibration, decision-making curve, and clinical usefulness of the radiomics nomogram were analyzed. The radiomic nomogram was validated using independent external cohort data. The areas under the receiver operating curve (AUC) were used to assess the predictive capability.
RESULTS Pathological examination confirmed MVI in 64 (28.9%), 22 (23.4%), and 16 (16.0%) of the 221, 94, and 100 patients, respectively. AFP, tumor size, non-smooth tumor margin, incomplete capsule, and peritumoral hypointensity in hepatobiliary phase (HBP) images had poor diagnostic value for MVI of sHCC. Quantitative radiomic features (1409) of MRI scans) were extracted. The classifier of logistic regression (LR) was the best machine learning method, and the radiomics scores of HBP and DWI had great diagnostic efficiency for the prediction of MVI in both the testing set (hospital A) and validation set (hospital B, C). The AUC of HBP was 0.979, 0.970, and 0.803, respectively, and the AUC of DWI was 0.971, 0.816, and 0.801 (P < 0.05), respectively. Good calibration and discrimination of the radiomics and clinical combined nomogram model were exhibited in the testing and two external validation cohorts (C-index of HBP and DWI were 0.971, 0.912, 0.808, and 0.970, 0.843, 0.869, respectively). The clinical usefulness of the nomogram was further confirmed using decision curve analysis.
CONCLUSION AFP and conventional Gd-EOB-DTPA-enhanced MRI features have poor diagnostic accuracies for MVI in patients with sHCC. Machine learning with an LR classifier yielded the best radiomics score for HBP and DWI. The radiomics nomogram developed as a noninvasive preoperative prediction method showed favorable predictive accuracy for evaluating MVI in sHCC.
Collapse
Affiliation(s)
- Yi-Di Chen
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ling Zhang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Peng Zhou
- Department of Radiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Bin Lin
- Department of Radiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Zi-Jian Jiang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Cheng Tang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yi-Wu Dang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 5350021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Wei Xia
- Department of Technology, Huiying Medical Technology (Beijing), Beijing 100192, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Ling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
|
9
|
Impact on Prognosis Following Nonanatomical Resection of Hepatocellular Carcinoma Postoperatively Proven as Micro Portal Vein Tumor Thrombus on Histology. Int Surg 2022. [DOI: 10.9738/intsurg-d-18-00018.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective
The prognostic impact of intrahepatic recurrence pattern and/or operative procedure (anatomical resection [AR] and nonanatomical resection [NAR]) for hepatocellular carcinoma (HCC) in patients with postoperatively proven portal vein tumor thrombus on histology has not yet been clearly examined.
Summary of background data
A total of 52 HCC patients who had no visible macroscopic vascular invasion preoperatively and histologically proven portal vein tumor thrombus distal to second-order portal branches after surgery were analyzed.
Methods
The overall survival and disease-free survival rates were analyzed using the Kaplan-Meier method. The risk factors for intrahepatic recurrence and distant metastasis were analyzed using the log-rank test.
Results
There was no significant difference in the overall survival rates at 5 years, based on the operative procedure. The disease-free survival rates at 3 years were 59.2% (AR group) and 30.1% (NAR group), respectively, and were statistically significant. Intrahepatic recurrence in the same remnant segment was seen in 5 patients undergoing NAR. These cases developed multiple bilobar recurrences simultaneously, including the same segment, and recurrence only in the same remnant segment was not seen in any case, irrespective of solitary or multiple recurrence.
Conclusions
Intrahepatic recurrence in the same remnant segment does not influence the disease-free survival rate in patients after NAR. Although AR would be an ideal procedure, the current study suggests NAR can achieve identical outcomes for patients who cannot be considered for AR.
Collapse
|
|
10
|
Barbosa BC, Santos LAR, Daher GHRM, Martins DL, Perales SR, Gallani SK, Costa LBEDA, Lago EAD, Boin IDEFSF, Caserta NMG, Ataíde ECDE. Clinical impact of the Model for End Liver Disease (MELD) score on the presence of microvascular invasion and on the postoperative outcome in patients undergoing liver transplantation. Rev Col Bras Cir 2021; 48:e20212997. [PMID: 34932735 PMCID: PMC10683444 DOI: 10.1590/0100-6991e-20212997] [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: 03/09/2021] [Accepted: 06/30/2021] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE to correlate clinical and epidemiological data with the pathological analysis of liver explants from patients undergoing liver transplantation for hetapocarcinoma in the UNICAMP HC and to verify whether the MELD and MELD-Na scores are reliable factors to predict a worse post-transplant prognosis. METHODS we studied liver transplants carried out between May 2010 and November 2017. After excluding 38 patients, we included 87, analyzing clinical and laboratory data for correlation with the outcome Microvascular Invasion (MVI). Subsequently, we computed the MELD and MELD-Na scores and performed a descriptive analysis of clinical and laboratory data and, finally, calculated ROC curves to assess the association between these laboratory parameters and mortality in these patients. RESULTS most patients were male (78.30%), with an average age of 58.53 years. Most liver diseases were caused by HCV (53.26%). We found no predictors for MVI among the laboratory parameters. The ROC curves for death identified the MELD score as the cutoff point with the highest combined sensitivity (90.91%) and specificity (37.50%), with a value of 10 points, whereas in the MELD-Na the cutoff point was 7 points, with a sensitivity of 90.91% and a specificity of 33.33%, both scores being significant. CONCLUSIONS there were no reliable predictors of MVI between clinical, laboratory, and epidemiological variables. The MELD-Na score is more sensitive than the MELD one for predicting mortality in patients undergoing liver transplantation.
Collapse
Affiliation(s)
- Brainner Campos Barbosa
- - PUC Goiás, Departamento de Medicina - Goiânia - GO - Brasil
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | | | | | - Daniel Lahan Martins
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | - Simone Reges Perales
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | - Stephanis Kilaris Gallani
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | - Larissa Bastos Eloy DA Costa
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | - Eduardo Andreazza Dal Lago
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | | | - Nelson Marcio Gomes Caserta
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| | - Elaine Cristina DE Ataíde
- - Universidade Estadual De Campinas (UNICAMP), Hospital das Clínicas da Universidade Estadual de Campinas (HC UNICAMP) - Campinas - SP - Brasil
| |
Collapse
|
|
11
|
Pan Y, Mei J, Chen J, Zhang D, Wang J, Wang X, Yi M, Zhou Z, Zhang Y, Chen M, Guo R, Xu L. Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma. Ann Surg Oncol 2021; 29:2016-2029. [PMID: 34637058 DOI: 10.1245/s10434-021-10903-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/19/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively. OBJECTIVE This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC. METHODS A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes. RESULTS Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy. CONCLUSIONS Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
Collapse
Affiliation(s)
- Yangxun Pan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden
| | - Jie Mei
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Jinbin Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Deyao Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Xiaohui Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minjiang Yi
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Rongping Guo
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
| |
Collapse
|
|
12
|
Increased Survival Benefit of Adjuvant Intra-arterial Infusion Chemotherapy in HCC Patients with Portal Vein Infiltration after Hepatectomy. World J Surg 2021; 44:2770-2776. [PMID: 32318792 DOI: 10.1007/s00268-020-05527-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of adjuvant hepatic intra-arterial infusion chemotherapy (HAI) is considered to be a promising option. METHODS We examined treatment effects of adjuvant HAI using cisplatin in 37 hepatocellular carcinoma (HCC) patients with portal vein infiltration (PVI) who underwent hepatectomy in comparison with those in 85 patients who did not. RESULTS PVI in 89 patients. Increased levels of aspartate transaminase, tumor markers, size and microvessel tumor infiltration (MVI) or cirrhosis, poorly differentiation, non-adjuvant HAI was associated with lower overall survival (p = 0.09). Poor differentiation, MVI and HAI were independently risk factors associated with tumor-free and overall survivals by the multivariate analysis (p < 0.05). Adjuvant HAI tended to show longer survivals in comparison with no-HAI (p = 0.08) and the multivariate analysis revealed significant efficacy of HAI for better prognosis. CONCLUSION Adjuvant HAI showed effectiveness on prolonging tumor-free and patient survival in HCC with PVI and is a promising option in the daily clinical practice.
Collapse
|
|
13
|
Chen G, Wang R, Zhang C, Gui L, Xue Y, Ren X, Li Z, Wang S, Zhang Z, Zhao J, Zhang H, Yao C, Wang J, Liu J. Integration of pre-surgical blood test results predict microvascular invasion risk in hepatocellular carcinoma. Comput Struct Biotechnol J 2021; 19:826-834. [PMID: 33598098 PMCID: PMC7848436 DOI: 10.1016/j.csbj.2021.01.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 01/07/2021] [Accepted: 01/08/2021] [Indexed: 12/12/2022] Open
Abstract
Microvascular invasion (MVI) is one of the most important factors leading to poor prognosis for hepatocellular carcinoma (HCC) patients, and detection of MVI prior to surgical operation could great benefit patient's prognosis and survival. Since it is still lacking effective non-invasive strategy for MVI detection before surgery, novel MVI determination approaches were in urgent need. In this study, complete blood count, blood test and AFP test results are utilized to perform preoperative prediction of MVI based on a novel interpretable deep learning method to quantify the risk of MVI. The proposed method termed as "Interpretation based Risk Prediction" can estimate the MVI risk precisely and achieve better performance compared with the state-of-art MVI risk estimation methods with concordance indexes of 0.9341 and 0.9052 on the training cohort and the independent validation cohort, respectively. Moreover, further analyses of the model outputs demonstrate that the quantified risk of MVI from our model could serve as an independent preoperative risk factor for both recurrence-free survival and overall survival of HCC patients. Thus, our model showed great potential in quantification of MVI risk and prediction of prognosis for HCC patients.
Collapse
Affiliation(s)
- Geng Chen
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Rendong Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Chen Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Lijia Gui
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yuan Xue
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xianlin Ren
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Zhenli Li
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Sijia Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Zhenxi Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Jing Zhao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Huqing Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Cuiping Yao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Jing Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| |
Collapse
|
|
14
|
Mohammadifard M, Ghanaati H, Mohammadifard M. A review of applying transarterial chemoembolization (TACE) method for management of hepatocellular carcinoma. J Family Med Prim Care 2021; 10:3553-3560. [PMID: 34934646 PMCID: PMC8653440 DOI: 10.4103/jfmpc.jfmpc_2347_20] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 06/16/2021] [Accepted: 06/28/2021] [Indexed: 12/09/2022] Open
Abstract
Liver cancer is one of the most ordinary reasons for death among cancers. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. In spite of the fact that various remedial methods have been approved particularly the survival effects of the transcatheter arterial chemoembolization (TACE) method have been accomplished widely in the HCC treatment. By applying the TACE method correctly, good survival outcomes can be achieved without harmfully affecting the hepatic functions. Transarterial chemoembolization mixes the effect of avascular necrosis (AVN) with the effect of regional chemotherapy those are under the influence of arterial embolization. By knowing the fact that the metastases of liver cancer and also perfusion indices in hepatocellular carcinoma (HCC) are via hepatic arteries, doctors chose the TACE method for the treatment of liver cancer. On the other hand, in this method, the radiologists can easily convey antitumor remedies via the arteries. Anyway, medium-level HCC is a sensitive stage of the heterogeneous disease that many patients suffer from, so specialists must consider it as a hazardous syndrome. The TACE procedure could be applied just in cases that the liver function of patients is appropriate yet, the patient liver portal vein do not have any problems and the patients do not have ascites disorder. This review is aimed to figure out the evident advantages of TACE especially by a comprehensive view on the medium level HCC. Because of that this treatment method is suggested as a first-line remedy. At last, the future landscape of the initial factors of research in managing HCC disorders have been summarized.
Collapse
|
|
15
|
CT Image-Based Texture Analysis to Predict Microvascular Invasion in Primary Hepatocellular Carcinoma. J Digit Imaging 2020; 33:1365-1375. [PMID: 32968880 DOI: 10.1007/s10278-020-00386-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 08/29/2020] [Accepted: 09/14/2020] [Indexed: 12/15/2022] Open
Abstract
The objective of this study was to determine the clinical value of computed tomography (CT) image-based texture analysis in predicting microvascular invasion of primary hepatocellular carcinoma (HCC). CT images of patients with HCC from May 2017 to May 2019 confirmed by surgery and histopathology were retrospectively analyzed. Image features including tumor margin, tumor capsule, peritumoral enhancement, hypoattenuating halo, intratumoral arteries, and tumor-liver differences were assessed. All patients were divided into microvascular invasion (MVI)-negative group (n = 34) and MVI-positive group (n = 68). Preoperative CT images were further imported into MaZda software, where the regions of interest of the lesions were manually delineated. Texture features of lesions based on pre-contrast, arterial, portal, and equilibrium phase CT images were extracted. Thirty optimal texture parameters were selected from each phase by Fisher's coefficient (Fisher), classification error probability combined with average correlation coefficient (POE+ACC), and mutual information (MI). Finally, receiver operating characteristic curve analysis was performed. The results showed that the Edmonson-Steiner grades, tumor size, tumor margin, and intratumoral artery characteristics were significantly different between the two groups (P = 0.012, < 0.001, < 0.001, = 0.003, respectively). There were 58 parameters with significant differences between the MVI-negative and MVI-positive groups (P < 0.001 for all). Among them, 12, 14, 17, and 15 parameters were derived from the pre-contrast phase, arterial phase, portal phase, and equilibrium phase respectively. According to the ROC analysis, optimal texture parameters based on the pre-contrast, arterial, portal, and equilibrium phases were 135dr_GLevNonU (AUC, 0.766; the cutoff value, 1055.00), Vertl_RLNonUni (AUC, 0.764; the cutoff value, 5974.38), 45dgr_GLevNonU (AUC, 0.762; the cutoff value, 924.34), and Vertl_RLNonUni (AUC, 0.754; the cutoff value, 4868.80), respectively. Texture analysis of preoperative CT images may be used as a non-invasive method to predict microvascular invasion in patients with primary hepatocellular carcinomas, and further to guide the treatment and evaluate prognosis. The most valuable parameters were derived from the gray-level run-length matrix.
Collapse
|
|
16
|
Hu XG, Shen XY, Nan JN, Kim IG, Yoon JK, Hong SY, Kim MN, Kim BW, Wang HJ. 18F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus. Ann Surg Treat Res 2020; 99:8-17. [PMID: 32676477 PMCID: PMC7332322 DOI: 10.4174/astr.2020.99.1.8] [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: 12/02/2019] [Revised: 03/07/2020] [Accepted: 04/07/2020] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT. METHODS Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT. RESULTS Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS. CONCLUSION SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.
Collapse
Affiliation(s)
- Xu-Guang Hu
- Division of Hepatobiliary Surgery and Intervention, Department of Surgery, Jiangxi Cancer Hospital, Nan Chang, China
| | - Xue-Yin Shen
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Jin-Niang Nan
- Department of Clinical Medicine, Jiangxi Health Career College of China, Nan Chang, China
| | - In-Gyu Kim
- Health Insurance Review and Assessment Service, Seoul, Korea
| | - Joon-Kee Yoon
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
| | - Sung-Yeon Hong
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Mi-Na Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Bong-Wan Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hee-Jung Wang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| |
Collapse
|
|
17
|
Gao Y, Wang PX, Cheng JW, Sun YF, Hu B, Guo W, Zhou KQ, Yin Y, Li YC, Wang J, Huang JF, Qiu SJ, Zhou J, Fan J, Yang XR. Chemotherapeutic perfusion of portal vein after tumor thrombectomy and hepatectomy benefits patients with advanced hepatocellular carcinoma: A propensity score-matched survival analysis. Cancer Med 2019; 8:6933-6944. [PMID: 31566899 PMCID: PMC6853833 DOI: 10.1002/cam4.2556] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 08/08/2019] [Accepted: 08/30/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.
Collapse
Affiliation(s)
- Yang Gao
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Peng-Xiang Wang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Jian-Wen Cheng
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Yun-Fan Sun
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Bo Hu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Wei Guo
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China
| | - Kai-Qian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Yue Yin
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Yuan-Cheng Li
- Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Jian Wang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Jun-Feng Huang
- Department of Intensive Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shuang-Jian Qiu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| | - Xin-Rong Yang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China
| |
Collapse
|
|
18
|
Liao M, Qin W, Liao Y, Yao R, Yu J, Liao W. Prognostic Value of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in Patients With Single Tumor Size ≤ 5 cm Hepatocellular Carcinoma After Radical Resection. Front Oncol 2019; 9:347. [PMID: 31165038 PMCID: PMC6536585 DOI: 10.3389/fonc.2019.00347] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 04/15/2019] [Indexed: 12/13/2022] Open
Abstract
Prediction of prognosis of hepatocellular carcinoma (HCC) has shown an important role in improving treatment outcomes and preventing disease progression, however, the prognostic indicator of HCC is still lacking. The purpose of this study is to investigate the predictive value of GLR (gamma-glutamyl transpeptidase to lymphocyte count ratio) in single HCC with a tumor size (TS) ≤ 5 cm. A retrospective analysis was performed on 272 patients with TS ≤ 5 cm who underwent radical resection. The Pearson χ2 test was applied to discuss the relationship between HCC and GLR, alpha-fetoprotein (AFP). Then univariate and multivariate analysis was utilized to predict the risk factors for survival prognosis in patients. In this study, GLR showed a positive relation with tumor size, tumor-node-metastasis (TNM) stage, microvascular invasion, early recurrence, and serum aspartate aminotransferase (AST) level, while the AFP value only correlated with drinking. Elevated GLR value had poor overall survival (OS) and progression-free survival (PFS) of TS ≤ 5 cm HCC patients, GLR level and tumor size were closely related to the prognosis of small HCC patients compared with AFP. GLR may serve as a prognostic marker for dynamic monitoring of HCC patients with single TS ≤ 5 cm after radical resection.
Collapse
Affiliation(s)
- Minjun Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China.,Oncology Medical College, Guangxi Medical University, Nanning, China
| | - Wanying Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yan Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China.,Disease Prevention and Control Center of Guilin, Guilin, China
| | - Renzhi Yao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Junxiong Yu
- Department of Anesthesiology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| |
Collapse
|
|
19
|
Chammas MC, Oliveira AC, D Ávilla MJ, Moraes PH, Takahashi MS. Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography. ULTRASOUND IN MEDICINE & BIOLOGY 2019; 45:50-55. [PMID: 30366607 DOI: 10.1016/j.ultrasmedbio.2018.09.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 09/08/2018] [Accepted: 09/12/2018] [Indexed: 06/08/2023]
Abstract
We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ = 0.903 (p < 0.0001), sensitivity = 91% and specificity = 100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.
Collapse
Affiliation(s)
- Maria C Chammas
- Ultrasound Division, Department of Radiology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Andre C Oliveira
- Liver Surgery Division, Department of Surgery, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Mario J D Ávilla
- Ultrasound Division, Department of Radiology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Pedro H Moraes
- Ultrasound Division, Department of Radiology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Marcelo Straus Takahashi
- Ultrasound Division, Department of Radiology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
| |
Collapse
|
|
20
|
Caspase-Cleaved Cytokeratin 18 Fragment M30 as a Potential Biomarker of Macrovascular Invasion in Hepatocellular Carcinoma. J Gastrointest Cancer 2018; 49:260-267. [PMID: 28361205 DOI: 10.1007/s12029-017-9937-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Extremely poor prognosis in hepatocellular carcinoma (HCC) patients with progressing disease was denoted by vascular invasion. Cytokeratin 18 (CK18) has been shown to be overexpressed in hepatocellular carcinoma so it is a valuable tumor marker; however, its role in vascular invasion is still unclear. This study aimed to predict CK18 as a predictive marker for macrovascular malignant invasion. METHODS The present study was conducted on three groups of patients: group I included 91 HCC patients without macrovascular invasion, group II included 34 HCC patients with radiological evidence of vascular invasion, and group III included 110 control individuals subdivided into IIIA as healthy blood donors and IIIB as post-HCV cirrhotic patients without HCC. RESULTS ROC curve of M30 fragments of CK18 was constructed for discrimination between HCC with and without macrovascular invasion. Optimum cutoff value was 304.5 ng/mL (AUC = 0.997, P < 0.001), sensitivity (100%) and specificity (98.8%). Regression analysis was conducted for prediction of macrovascular invasion within HCC patients. The following variables: higher levels of AST, M30, bilirubin, and AFP, lower levels of serum albumin, larger tumor size, child B score, and multiple lesions were associated with vascular invasion in univariate analysis. While in multivariate analysis, higher levels of AST and bilirubin and elevated levels of M30 and AFP serum were considered independent predictors for macrovascular invasion in HCC patients. CONCLUSION The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.
Collapse
|
|
21
|
Reginelli A, Vacca G, Segreto T, Picascia R, Clemente A, Urraro F, Serra N, Vanzulli A, Cappabianca S. Can microvascular invasion in hepatocellular carcinoma be predicted by diagnostic imaging? A critical review. Future Oncol 2018; 14:2985-2994. [PMID: 30084651 DOI: 10.2217/fon-2018-0175] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Imaging still has a limited capacity to detect microvascular invasion (mVI). The objective of this critical review is the evaluation of the most significant predictors of mVI in hepatocellular carcinoma (HCC) detectable by computed tomography, PET/computed tomography and MRI using a mathematical model. We systematically reviewed 15 observational studies from 2008 to 2018 to analyze factors with most impact on mVI detection. The most significant predictors of mVI correlating with imaging techniques were considered. From 1902 patients considered, we individuated 30 total predictors of mVI in a multivariate analysis. The most frequent predictors related to the highest presence with mVI in HCC were: α-fetoprotein (p < 0.0001), tumor size (p < 0.0001) and number of HCC nodules (p = 0.0020).
Collapse
Affiliation(s)
- Alfonso Reginelli
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Giovanna Vacca
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Teresa Segreto
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Roberto Picascia
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Alfredo Clemente
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Fabrizio Urraro
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | - Nicola Serra
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| | | | - Salvatore Cappabianca
- Department of Radiology & Radiotherapy, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, Naples 80138, Italy
| |
Collapse
|
|
22
|
Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:9674565. [PMID: 29606926 PMCID: PMC5828041 DOI: 10.1155/2018/9674565] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 11/26/2017] [Accepted: 12/20/2017] [Indexed: 12/16/2022]
Abstract
Objective To investigate the imaging features observed in preoperative Gd-EOB-DTPA-dynamic enhanced MRI and correlated with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods 66 HCCs in 60 patients with preoperative Gd-EOB-DTPA-dynamic enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, peritumor enhancement during mid-arterial phase, peritumor hypointensity during hepatobiliary phase, signal intensity ratio on DWI and apparent diffusion coefficients (ADC), T1 relaxation times, and the reduction rate between pre- and postcontrast enhancement images were assessed. Correlation between these features and histopathological presence of MVI was analyzed to establish a prediction model. Results Histopathology confirmed that MVI were observed in 17 of 66 HCCs. Univariate analysis showed tumor size (p = 0.003), margin (p = 0.013), peritumor enhancement (p = 0.001), and hypointensity during hepatobiliary phase (p = 0.004) were associated with MVI. A multiple logistic regression model was established, which showed tumor size, margin, and peritumor enhancement were combined predictors for the presence of MVI (α = 0.1). R2 of this prediction model was 0.353, and the sensitivity and specificity were 52.9% and 93.0%, respectively. Conclusion Large tumor size, irregular tumor margin, and peritumor enhancement in preoperative Gd-EOB-DTPA-dynamic enhanced MRI can predict the presence of MVI in HCC.
Collapse
|
|
23
|
Beppu T, Nakagawa S, Nitta H, Okabe H, Kaida T, Imai K, Hayashi H, Koga Y, Kuramoto K, Hashimoto D, Yamashita YI, Chikamoto A, Ishiko T, Baba H. The Number of Positive Tumor Marker Status Is Beneficial for the Selection of Therapeutic Modalities in Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:165-168. [PMID: 28660154 PMCID: PMC5472937 DOI: 10.14218/jcth.2016.00055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 04/11/2017] [Accepted: 04/13/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC). Alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-c-carboxy prothrombin are well-known and useful tumor markers for HCC. The positive number status of these tumor markers has recently been demonstrated as beneficial for predicting outcome for HCC patients treated with local therapy. Although the normal ranges reported have differed by institution, the positivity of tumor markers is consistent and can easily be assessed. Kumamoto and Wakayama's group clearly demonstrated the following: 1) Regardless of the degree of tumor stage, a triple-positive tumor marker profile can predict poor outcome in HCC patients undergoing HR; 2) For RFA alone, HCC patients with double- and triple-positive status, having less than three lesions and lesions ≤3 cm in diameter show comparably insufficient outcomes; 3) For HCC patients with lesions ≤5 cm in Child-Pugh grade A, HR is preferred over RFA; 4) Microvascular invasion rates increased even in the double-positive patients, while poorly differentiated HCC was frequently observed only in the triple-positive patients; and 5) RFA with chemoembolization, anatomical liver resection, and postoperative adjuvant chemoembolization or hepatic arterial chemotherapy might improve the outcome for patients with highly malignant HCC with multiple positive tumor markers. However, the impacts of these therapies still need to be evaluated in prospective comparative studies.
Collapse
Affiliation(s)
- Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
- *Correspondence to: Toru Beppu, Department of Surgery, Yamaga City Medical Center, 511, Yamaga, Kumamoto 861-0593, Japan. Tel: +81-968-44-2185, Fax: +81-968-44-2420, E-mail:
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuki Koga
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kunitaka Kuramoto
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
|
24
|
Liu M, Wang L, Zhu H, Rong W, Wu F, Liang S, Xu N, Wu J. A Preoperative Measurement of Serum MicroRNA-125b May Predict the Presence of Microvascular Invasion in Hepatocellular Carcinomas Patients. Transl Oncol 2016; 9:167-72. [PMID: 27267832 PMCID: PMC4856864 DOI: 10.1016/j.tranon.2016.03.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 03/03/2016] [Accepted: 03/03/2016] [Indexed: 02/07/2023] Open
Abstract
The high recurrence rate remains a major problem that strongly influenced the prognosis of hepatocellular carcinoma (HCC) patients who received hepatectomy. The presence of microvascular invasion (MVI) is regarded as the most important risk factor that contributes to the postoperative recurrence. Our previous study has hinted that serum microRNA-125b (miR-125b) was associated with MVI. The aim of the present study was to identify whether serum miR-125b can serve as a biomarker to reliably predict microvascular invasion (MVI) preoperatively. MiR-125b was quantified in 108 HCC patients’ serum before they received surgery by quantitative real-time PCR (qRT-PCR). Our results revealed that MVI was associated with relapse free survival (RFS) of postoperative HCC patients; surgical margin width was associated with postoperative RFS in MVI present patients, but not in the patients without MVI. Multivariate analysis revealed that miR-125b, tumor size and AFP were the independent predictive factors associated with MVI in this cohort (P = .001, .001, .003, respectively). The probability of the predictive accuracy of miR-125b was 76.95% (51.32% specificity and 87.50% sensitivity), which was almost equal to the classifier established by combination of AFP and tumor size (78.82% probability, 65.63% specificity and 84.21% sensitivity). Furthermore, the combination of tumor size, AFP and miR-125b yielded a ROC curve area of 86.68% (72.37% specificity and 84.38% sensitivity). Our study indicated that serum miR-125b can be used to predict MVI of HCC patients before they received hepatic resection. Therefore, miR-125b can potentially guide individualized treatment, which helps HCC patients, with or without MVI, to benefit from different surgical approach.
Collapse
Affiliation(s)
- Mei Liu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China
| | - Liming Wang
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China
| | - Hongxia Zhu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China
| | - Weiqi Rong
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China
| | - Fan Wu
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China
| | - Shufang Liang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No. 17, 3rd Section of People's South Road, Chengdu, 610041, P.R. China
| | - Ningzhi Xu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No. 17, 3rd Section of People's South Road, Chengdu, 610041, P.R. China.
| | - Jianxiong Wu
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
| |
Collapse
|
|
25
|
Jin Y, Zhou L, Liang ZY, Jin KM, Zhou WX, Xing BC. Clinicopathologic and Prognostic Significance of Carboxyl Terminus of Hsp70-interacting Protein in HBV-related Hepatocellular Carcinoma. Asian Pac J Cancer Prev 2016; 16:3709-13. [PMID: 25987026 DOI: 10.7314/apjcp.2015.16.9.3709] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)- related HCC remain unknown. MATERIALS AND METHODS CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. RESULTS It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. CONCLUSIONS CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.
Collapse
Affiliation(s)
- Ye Jin
- Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China E-mail :
| | | | | | | | | | | |
Collapse
|
|
26
|
Sun JX, Shi J, Li N, Guo WX, Wu MC, Lau WY, Cheng SQ. Portal vein tumor thrombus is a bottleneck in the treatment of hepatocellular carcinoma. Cancer Biol Med 2016; 13:452-458. [PMID: 28154776 PMCID: PMC5250602 DOI: 10.20892/j.issn.2095-3941.2016.0059] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The effect of portal vein tumor thrombus (PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: “hepatocellular carcinoma” AND “portal vein tumor thrombus.” Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy (RT), transhepatic arterial chemoembolization (TACE), transarterial radioembolization (TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT, TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.
Collapse
Affiliation(s)
- Ju-Xian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Nan Li
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| | - Wan-Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgical Hospital, Shanghai 200438, China
| |
Collapse
|
|
27
|
Feng Y, Qin XC, Luo Y, Li YZ, Zhou X. Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:1553-1560. [PMID: 25747937 DOI: 10.1016/j.ultrasmedbio.2015.01.026] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 01/18/2015] [Accepted: 01/26/2015] [Indexed: 06/04/2023]
Abstract
The aim of this retrospective study was to evaluate the efficacy of contrast-enhanced ultrasound (CEUS) washout rate in predicting hepatocellular carcinoma (HCC) differentiation. Two hundred seventy-one patients underwent liver resection for HCC between April 2008 and December 2012 after being examined by CEUS using the contrast agent SonoVue with a low mechanical index (<0.1) in a routine procedure. Contrast agent washout rates obtained from video images were divided into four categories from slow to fast: WR1 = no washout in all phases (slowest); WR2 = washout after 120 s from contrast injection (late-phase washout); WR3 = washout between 41 and 120 s from contrast injection (portal venous washout); WR4 = washout before 40 s from contrast injection (fastest washout rate). HCC nodules were graded as well, moderately and poorly differentiated. Spearman rank correlation and χ(2)-tests were used to assess group relationships and differences. Receiver operating characteristic curve analysis was used to determine the diagnostic predictive value of CEUS. Among the 271 patients, 18 (6.6%) had well differentiated, 150 (55.4%) had moderately differentiated and 103 (38.0%) had poorly differentiated HCC. Statistical tests indicated that washout rate was significantly correlated with tumor differentiation (p < 0.05), and the poorly differentiated HCCs had earlier washout. At the cutoff point of WR4, CEUS based on washout rate performed poorly in distinguishing poorly differentiated from moderately and well-differentiated HCCs, with a sensitivity, specificity and accuracy (area under the curve) of 24%, 97% and 0.68, respectively. However, at the cutoff point of WR2, the sensitivity, specificity and accuracy of CEUS in differentiating well-differentiated HCC from other HCCs were significantly better: 98%, 78% and 0.96, respectively. Thus, CEUS washout rate may have a role in identifying patients with well-differentiated HCC.
Collapse
Affiliation(s)
- Yan Feng
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Medical Imaging Pharmaceutical Lab, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xia-Chuan Qin
- Ultrasound Department, Nanchong Central Hospital, Nanchong, Sichuan Province, China
| | - Yan Luo
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yong-Zhong Li
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiang Zhou
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Medical Imaging Pharmaceutical Lab, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| |
Collapse
|
|
28
|
Lee DH, Lee JM, Lee JY, Kim SH, Kim JH, Yoon JH, Kim YJ, Lee JH, Yu SJ, Han JK, Choi BI. Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation. J Hepatol 2015; 62:1122-30. [PMID: 25529623 DOI: 10.1016/j.jhep.2014.12.015] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 11/27/2014] [Accepted: 12/09/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Hepatobiliary phase images (HBPI) of gadoxetic acid-enhanced MRI can depict borderline hepatocellular nodules that have the potential to progress into hypervascular hepatocellular carcinomas (HCCs), as non-hypervascular hypointense nodules. We retrospectively evaluated the impact of the presence of non-hypervascular hypointense nodules at HBPI of gadoxetic acid-enhanced MRI on the patient's prognosis after radiofrequency ablation (RFA) for early stage HCCs. METHODS A total of 139 patients who underwent pre-procedural gadoxetic acid-enhanced MRI followed by RFA were included. After a mean follow-up of 44.6±13.2 months, we compared the results of tumor recurrence as well as overall and recurrence-free survival (RFS) with the presence of non-hypervascular hypointense nodules on HBPI. RESULTS The presence of non-hypervascular hypointense nodules on HBPI did not affect overall survival (p=0.136). However, the estimated 5-year RFS rate was 71.3% in 29 patients without non-hypervascular hypointense nodules on HBPI compared to 27.9% in 110 patients with non-hypervascular hypointense nodules on HBPI, indicating a significant difference (hazard ratio=2.84 [1.39-5.98], p=0.006). When we classified recurrence into local tumor progression [LTP], intrahepatic distant recurrence [IDR], and extra-hepatic metastasis [EM], five-year cumulative incidences (CI) of IDR in patients with non-hypervascular hypointense nodules on HBPI were significantly higher than those in patients without non-hypervascular hypointense nodules on HBPI (17.9% vs. 67.5%, p<0.001). Five-year CIs of LTP and EM showed no significant difference (p>0.05). CONCLUSIONS The presence of non-hypervascular hypointense hepatocellular nodules on HBPI of gadoxetic acid-enhanced MRI taken prior to RFA is a significant predictive factor of recurrence after RFA of early stage HCCs, particularly IDR.
Collapse
Affiliation(s)
- Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea.
| | - Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea
| | - Se Hyung Kim
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea
| | - Jung Hwan Yoon
- Department of Internal Medicine, Seoul National University Hospital, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine, Seoul National University Hospital, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University Hospital, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University Hospital, Republic of Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea
| | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Republic of Korea; Institute of Radiation Medicine, Seoul National University Hospital, Republic of Korea
| |
Collapse
|
|
29
|
The impact of posthepatectomy liver failure on the recurrence of hepatocellular carcinoma. World J Surg 2014; 38:150-8. [PMID: 24132820 DOI: 10.1007/s00268-013-2247-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) who underwent hepatectomy often developed an intrahepatic recurrence, even though it was a curative one. The relationship between surgery-induced liver damage and the recurrence of HCC has not been described. This study evaluated whether posthepatectomy liver failure, as defined by the International Study Group of Liver Surgery, affected the recurrence of HCC. METHODS We performed a retrospective cohort study of 488 patients with HCC who underwent hepatectomy between 2004 and 2012 at Kyoto University Hospital. Early posthepatectomy liver failure (EPLF) was defined as liver failure occurring between postoperative days 5 and 10. The patients were divided into an EPLF group and a non-EPLF group. Disease-free survival (DFS) was compared between these groups. The influences of host-related, surgery-related, and tumor-related factors on patient outcomes were evaluated using multivariate analyses. RESULTS The EPLF group and the non-EPLF group contained 153 and 335 patients, respectively. The probability of DFS was significantly increased in the non-EPLF group (median: 574 days) compared to the EPLF group (median: 348 days) (hazard ratio, HR [95 % confidence interval, CI] 1.61 [1.29-2.00]). The multivariate analysis revealed that EPLF was an independent factor for DFS (HR [95 % CI] 1.43 [1.13-1.81]), besides the factors previously described, including fibrosis (1.32 [1.05-1.67]), stage (1.85 [1.34-2.51]), tumor differentiation (1.46 [1.11-1.89]), and des-γ-carboxyprothrombin (1.39 [1.10-1.74]). CONCLUSIONS EPLF was associated with postoperative HCC recurrence. The prevention of EPLF might improve the prognosis of patients with HCC.
Collapse
|
|
30
|
Abstract
GOALS/BACKGROUND Macrovascular invasion (MaVI) is often detected by radiologic imaging in hepatocellular carcinoma (HCC) patients and may affect their long-term survival. We aimed to investigate the prevalence, determinants, and prognostic impact of MaVI in patients with HCC receiving curative and noncurative therapies. STUDY A total of 2654 HCC patients in a single center were identified. The risk factors and prognostic determinants of MaVI were determined. RESULTS A total of 928 (35%) patients had MaVI. Old age, lower serum α-fetoprotein level, higher serum sodium level, good performance status, smaller total tumor volume, and better liver functional reserve were significantly associated with a lower risk for VI. In the Cox proportional hazards model, patients with lower serum albumin level, higher serum bilirubin and α-fetoprotein level, worse performance status, the presence of ascites, and MaVI independently predicted a decreased long-term survival in patients undergoing both curative and noncurative treatments. In addition, lower sodium level and larger tumor size were independently associated with a poor outcome in the noncurative treatment group. Of the patients with MaVI, the 1-year survival rates for patients receiving surgical treatment, local ablation, transarterial chemoembolization, and supportive care were 83%, 75%, 57%, and 24%, respectively (P<0.001). CONCLUSIONS MaVI represents a distinct tumor phenotype of HCC and is associated with younger age, aggressive tumor behavior, poor liver functional reserve, and poor performance status. It adversely affects the survival of HCC patients independent of treatment strategy. Intensive anticancer therapy should be proposed to achieve a better long-term survival for the at-risk patients.
Collapse
|
|
31
|
Liu D, Fong DYT, Chan ACY, Poon RTP, Khong PL. Hepatocellular carcinoma: surveillance CT schedule after hepatectomy based on risk stratification. Radiology 2014; 274:133-40. [PMID: 25162308 DOI: 10.1148/radiol.14132343] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE To evaluate alternative schedules for surveillance computed tomography (CT) for patients who underwent hepatectomy for hepatocellular carcinoma ( HCC hepatocellular carcinoma ) and to demonstrate an appropriate schedule on the basis of stratification for risk of recurrence. MATERIALS AND METHODS CT and pathologic reports for consecutive patients with HCC hepatocellular carcinoma who underwent hepatectomy at one institution were evaluated with institutional review board approval. Univariate and multivariate analyses were performed to identify risk factors for recurrence. Patients were categorized into risk groups on the basis of classification and regression tree analysis. Average recurrence detection rates ( RDR recurrence detection rate s) between consecutive CT scans were calculated for existing and alternative surveillance schedules for each risk group, and the difference in RDR recurrence detection rate was determined by using the Student t test. A P value of less than .05 was considered to indicate a significant difference. Expected delay in diagnosis was also computed for the alternative surveillance schedules for each risk group. RESULTS Two hundred sixty patients (216 men; mean age, 56.0 years ± 22.5) underwent 2705 CT studies. Independent risk factors for recurrence were microvascular invasion (P = .001), cirrhosis (P = .007), and tumor multiplicity (P = .001). Three risk groups (low, intermediate, and high) were identified. For low- and intermediate-risk groups, average RDR recurrence detection rate was not significantly different in the first 2 years after hepatectomy when the interval was extended from 3 months (3.3% and 4.6%, respectively) to 4 months (4.3% [expected delay, 16 days] and 6.1% [expected delay, 18 days], respectively) or for the subsequent 3 years when the interval was extended from 6 months (1.3% and 3.5%, respectively) to 12 months (2.5% [expected delay, 72 days] and 7.0% [expected delay, 103 days], respectively). This alternative schedule included five (35.7%) fewer CT scans than the 14 in the original schedule, and a reduction in radiation dose and cost during the 5-year follow-up period. CONCLUSION Posthepatectomy surveillance CT schedules may be tailored and optimized according to stratification by risk of recurrence to reduce the frequency of CT scans without compromising surveillance benefits.
Collapse
Affiliation(s)
- Dan Liu
- From the Departments of Diagnostic Radiology (D.L., P.L.K.) and Surgery (A.C.Y.C., R.T.P.P.), Queen Mary Hospital, University of Hong Kong, 102 Pokfulam Rd, Hong Kong; and School of Nursing, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (D.Y.T.F.)
| | | | | | | | | |
Collapse
|
|
32
|
Adjuvant and chemopreventive therapies for resectable hepatocellular carcinoma: a literature review. Tumour Biol 2014; 35:9459-68. [PMID: 25119592 DOI: 10.1007/s13277-014-2443-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 08/04/2014] [Indexed: 01/27/2023] Open
Abstract
The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results.
Collapse
|
|
33
|
Portolani N, Baiocchi GL, Molfino S, Benetti A, Gheza F, Giulini SM. Microvascular infiltration has limited clinical value for treatment and prognosis in hepatocellular carcinoma. World J Surg 2014; 38:1769-1776. [PMID: 24378549 DOI: 10.1007/s00268-013-2426-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Microvascular infiltration (MVI) is considered a necessary step in the metastatic evolution of hepatocellular carcinoma (HCC), but its prognostic value after liver resection (LR) is uncertain. We studied the clinical value of MVI compared to the Milan criteria in a consecutive series of patients submitted to radical LR. METHODS A total of 441 patients were retrospectively evaluated. MVI and the Milan criteria were analyzed and compared as prognostic factors for overall and disease-free survival (DFS). RESULTS MVI was present in 189 patients (42.8 %). Grading, satellitosis, size of cancer, and alfa fetoprotein value were significantly related to MVI, which was present in 34.3 and 53.2 % of Milan+ and Milan- patients, respectively (p = 0.00001). Both MVI and the Milan criteria were associated with a lower overall and DFS, but only the Milan criteria were associated with the rate of early recurrence and the feasibility of a curative treatment of the recurrence. The application of MVI parameters to patients classified by the Milan criteria further selects the outcome in Milan+ patients (5-year survival rate of 54.1 and 67.9 %, respectively, in the presence or absence of MVI) but not in Milan- patients. CONCLUSIONS MVI is related to survival after LR for HCC, but the clinical value of this information is limited. In Milan+ patients, the absence of MVI selects the cases with better prognosis. In the presence of a liver recurrence, the Milan criteria related to the primary HCC show a better prognostic accuracy and have clinical relevance in the decision-making process.
Collapse
Affiliation(s)
- Nazario Portolani
- Department of Clinical and Experimental Sciences - Surgical Clinic, University of Brescia, Brescia, Italy
| | | | | | | | | | | |
Collapse
|
|
34
|
Zhou L, Liao Y, Yin P, Zeng Z, Li J, Lu X, Zheng L, Xu G. Metabolic profiling study of early and late recurrence of hepatocellular carcinoma based on liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 966:163-70. [PMID: 24582150 DOI: 10.1016/j.jchromb.2014.01.057] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 01/01/2014] [Accepted: 01/30/2014] [Indexed: 12/12/2022]
Abstract
The objectives of this pilot study were to predict early postoperative recurrence in hepatocellular carcinoma (HCC) patients based on metabolic features and to explore the related metabolic disturbances. Liquid chromatography-mass spectrometry-based metabolic profiling was performed on the plasma of 18 late recurrent and 22 early recurrent HCC patients. Metabolic differences were found to be related to amino acid, bile acid, cholesterol, fatty acid, phospholipid and carbohydrate metabolism. Bile acids, steroids and fatty acids showed significant variation in the early recurrent HCC group compared to the late recurrence group. Decreased levels of polyunsaturated eicosapentaenoic acid, docosahexaenoic acid and linolenic acid were found to be specific metabolic features for early recurrence. With the combination of methionine, GCDCA and cholesterol sulfate, 85% of the early recurrent HCCs can be predicted correctly with the corresponding area under the curve (AUC) equal to 0.95 in the training set, and 80% of the early recurrent HCCs can be predicted correctly with the corresponding AUC equal to 0.91 in the test set.
Collapse
Affiliation(s)
- Lina Zhou
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Yuan Liao
- State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, PR China
| | - Peiyuan Yin
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Zhongda Zeng
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Jia Li
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Xin Lu
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Limin Zheng
- State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, PR China
| | - Guowang Xu
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
| |
Collapse
|
|
35
|
Du M, Chen L, Zhao J, Tian F, Zeng H, Tan Y, Sun H, Zhou J, Ji Y. Microvascular invasion (MVI) is a poorer prognostic predictor for small hepatocellular carcinoma. BMC Cancer 2014; 14:38. [PMID: 24460749 PMCID: PMC3922738 DOI: 10.1186/1471-2407-14-38] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Accepted: 01/21/2014] [Indexed: 12/13/2022] Open
Abstract
Background Small hepatocellular carcinoma (SHCC) is a special type of hepatocellular carcinoma with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. However, the prognostic factors for SHCC remain controversial. The purpose of this study is to clarify the predictive factors of SHCC. Methods The study population consisted of 458 patients underwent hepatectomy for single SHCC between January 2006 and December 2008. Clinical data (included age, gender, virus infection, serum alfa-fetoprotein level, cirrhosis, capsule, border), histopathologic features (included differentiation, morphology subtype, microvascular invasion, tumor infiltrative lymphocytes (TIL), inflammatory injury grade and fibrosis stage of surrounding liver), were evaluated to identify prognostic factors influencing SHCC patients’ survival and microvascular invasion. Results There were 384 males (83.8%) and 74 (16.2%) females with median ages of 52 years. The median progression-free survival (PFS) and overall survival (OS) durations were 53 and 54 months, respectively. About 91.9% (n = 421) SHCC were infected by Hepatitis B. One hundred forty-seven of the 446 (33.0%) patients with pre-operation serum AFP level record had serum alfa-fetoprotein (AFP) level ≥ 200 ug/ml and 178 of the 280 (63.8%) patients with post-operation serum AFP level record had AFP level ≥ 20 ug/ml. Liver cirrhosis was present in 411 cases (89.7%), while 434 (97.3%) tumors had clear border, and 250 (55.6%) tumors were encapsulated. MVI was identified in 83 patients (18.1%). In univariate analysis, a significant association between the presence of MVI and shortened PFS and OS was found (p = 0.012, 0.028, respectively). Histological differentiation had strong relationship with MVI (p = 0.009), in terms of MVI was more easily presented in patients with worse histological differentiation. In patients with MVI, worse survival was correlated with female patients, patients with G2 or G3 histological differentiation, pre-operation serum AFP level ≥ 200 ug/ml or post-operation serum AFP level ≥ 20 ug/ml, and TIL ≥ 50/HPF. Conclusions MVI is an independent poorer prognostic factor for PFS and OS of single SHCC patients. Tumor histological differentiation was closely related with MVI.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| |
Collapse
|
|
36
|
Jia WD, Liu WB. Comprehensive treatment for hepatocellular carcinoma in patients at a high risk of recurrence after hepatectomy. Shijie Huaren Xiaohua Zazhi 2013; 21:3183-3189. [DOI: 10.11569/wcjd.v21.i30.3183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is high in China. Hepatectomy is the first choice for some HCC patients at a high risk of recurrence; however, the rate of postoperative recurrence in these patients remains high. Since single postoperative treatment trying to avoid recurrence often does not work effectively, more than one means are needed to reduce the recurrence on the basis of understanding the effectiveness of different therapeutic methods. In this paper, we will discuss the origin and molecular mechanisms of recurrence as well as the related treatments for HCC at a high risk of recurrence, with an aim to explore more effective and reasonable comprehensive treatments to prevent recurrence in HCC patients at a high risk of recurrence after hepatectomy.
Collapse
|
|
37
|
Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion. World J Surg 2013; 37:1034-42. [PMID: 23435678 DOI: 10.1007/s00268-013-1957-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The prognosis of hepatocellular carcinoma (HCC) with macroscopic vascular invasion is extremely poor even after hepatic resection. We aimed to clarify the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with vascular invasion. METHODS A total of 73 HCC patients with macroscopic vascular invasion were divided into two groups: 38 with hepatectomy with HAI (HAI group) and 35 with hepatectomy alone (non-HAI group). From 1997 to 2007, HAI was performed via an implanted injection port. The treatment comprised three courses of weekly infusion of HAI, which comprised cisplatin (10 mg daily on days 1-5) followed by 5-fluorouracil (5-FU; 250 mg daily on days 1-5) infusion. From 2007, cisplatin (60 mg/m(2)), 5-FU (600 mg/m(2)), and a mixture of mitomycin C (3 mg/m(2)) and degradable starch microspheres were administered for two courses. RESULTS Overall, 92 % of patients completed adjuvant HAI. In the HAI and non-HAI groups, the 5-year disease-free survival (DFS) rates were 33.1 % and 11.8 %, respectively (p = 0.029), and the 5-year overall survival (OS) rates were 46.7 % and 32.7 %, respectively (p = 0.318). Among the patients with Vp3/4 or Vv3 (n = 32) in the HAI group, the 3-year DFS and OS rates were 33.7 % and 56.8 %, respectively (p = 0.049). Those in the non-HAI group were 8.3 % and 12.0 %, respectively (p = 0.023). Cox proportional multivariate analysis for DFS revealed that HAI was an independent favorable prognostic factor in all 73 patients (hazard ratio 0.536; p = 0.029). CONCLUSIONS Adjuvant HAI for HCC patients with vascular invasion might reduce the risk of recurrence.
Collapse
|
|
38
|
Huang J, Zhang Y, Peng Z, Gao H, Xu L, Jiao LR, Chen M. A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy. J Cancer Res Clin Oncol 2013; 139:1709-19. [PMID: 23982274 DOI: 10.1007/s00432-013-1497-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 08/15/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the accuracy of the 7th edition of the American Joint Committee on Cancer staging system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and to propose a modified TNM system for better prediction of survival. METHODS Clinico-pathological data for 1,313 patients who underwent hepatectomy as initial treatment for HCC between 2000 and 2008 were retrieved from a prospective database. Overall survival (OS) and disease-free survival (DFS) were analyzed to evaluate the predictive value. RESULTS The 1-, 3-, 5-year OS and DFS of 1,313 patients were 79.2, 55.4, 45.5 %, and 52.6, 36.1, 31.8 %, respectively. Multivariate analysis revealed that major vascular invasion was the most important prognostic factor for both OS and DFS, along with tumour number and size. Patients with pT1 and pT2 disease had significantly better OS and DFS than those with pT3 disease (P < 0.001). There was no significant difference between pT3a and pT4 (P = 0.552) but patients with pT3b disease had a worse OS and DFS than those with pT4 disease (P = 0.006 and P < 0.001, respectively). A modified TNM system within the existing framework was proposed to combine the current pT3a and pT4 together as the new pT3 and to change pT3b to the new pT4. Analysis showed that this modified system had a better prognostic power than either TNM-6 or TNM-7. CONCLUSION TNM-7 would seem to be inaccurate for staging advanced HCC. The modified system can improve both the prognostic accuracy and the hazard discrimination of disease to be consistent among subgroups of HCC.
Collapse
Affiliation(s)
- Junting Huang
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Chan ACY, Fan ST, Poon RTP, Cheung TT, Chok KSH, Chan SC, Lo CM. Evaluation of the seventh edition of the American Joint Committee on Cancer tumour-node-metastasis (TNM) staging system for patients undergoing curative resection of hepatocellular carcinoma: implications for the development of a refined staging system. HPB (Oxford) 2013; 15:439-48. [PMID: 23659567 PMCID: PMC3664048 DOI: 10.1111/j.1477-2574.2012.00617.x] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Accepted: 08/30/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES This study aimed to evaluate the seventh edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system and to compare its efficacy with those of the fifth and sixth editions of the AJCC staging system and the TNM staging system defined by the Liver Cancer Study Group of Japan. METHODS Data for 754 patients submitted to hepatectomy for hepatocellular carcinoma (HCC) between 1989 and 2005 were reviewed. Tumour-free survival was estimated using the Kaplan-Meier method and compared between subgroups using the log-rank test. Prognostic factors for tumour-free survival were identified by multivariable analysis. The accuracy of these staging systems was evaluated using the Cox regression model and a refined staging system was developed based on the drawbacks of the respective systems. RESULTS According to the criteria defined by the seventh AJCC TNM staging system, 5-year survival was 50.6% in patients with T1 tumours, 21.0% in patients with T2 tumours, 14.6% in patients with T3a tumours, 12.1% in patients with T3b tumours, and 12.9% in patients with T4 tumours. There was no survival difference between patients with T3a and T3b tumours (P = 0.073), nor between those with T3b and T4 tumours (P = 0.227). Significant prognostic tumour factors were microvascular invasion, tumour multiplicity, bilobar disease and a tumour size of ≥5.0 cm. The fifth and sixth editions of the AJCC TNM staging system were found to be more accurate in prognosis than the seventh. CONCLUSIONS The seventh edition of the AJCC TNM staging system is able to adequately stratify patients with early HCC only. A refined staging system is therefore proposed.
Collapse
Affiliation(s)
- Albert C Y Chan
- Department of Surgery, University of Hong KongHong Kong, China
| | - Sheung Tat Fan
- Department of Surgery, University of Hong KongHong Kong, China,State Key Laboratory for Liver Research, University of Hong KongHong Kong, China,Correspondence Sheung Tat Fan, Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, 102 Pokfulam Road, Hong Kong, China. Tel: + 852 2 255 4703. Fax: + 852 2 986 5262. E-mail:
| | - Ronnie T P Poon
- Department of Surgery, University of Hong KongHong Kong, China,State Key Laboratory for Liver Research, University of Hong KongHong Kong, China
| | - Tan To Cheung
- Department of Surgery, University of Hong KongHong Kong, China
| | | | - See Ching Chan
- Department of Surgery, University of Hong KongHong Kong, China,State Key Laboratory for Liver Research, University of Hong KongHong Kong, China
| | - Chung Mau Lo
- Department of Surgery, University of Hong KongHong Kong, China,State Key Laboratory for Liver Research, University of Hong KongHong Kong, China
| |
Collapse
|
|
40
|
Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma. Eur J Surg Oncol 2013; 39:858-64. [PMID: 23669199 DOI: 10.1016/j.ejso.2013.04.003] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 03/26/2013] [Accepted: 04/25/2013] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The preoperative predictors of microvascular invasion (MVI) in multinodular hepatocellular carcinoma (HCC) are currently unclear. METHODS We retrospectively analyzed 266 patients who underwent potentially curative resection of multinodular HCC. MVI was diagnosed on pathological examination in 64 patients. Preoperative risk factors for MVI were identified and survival curves were analyzed. RESULTS Patients with MVI had significantly lower overall and recurrence-free survival rates than those without MVI (overall survival, 1 year: 86% vs. 71%, 3 years: 58% vs. 16%; recurrence-free survival, 1 year: 69% vs. 12%; 3 years: 48% vs. 12%; both P < 0.001). Multivariate analysis showed that serum alpha-fetoprotein (AFP) level >400 μg/L (odds ratio [OR] = 3.732, P = 0.016), serum gamma-glutamyltransferase (GGT) level >130 U/L (OR = 19.779, P < 0.001), total tumor diameter >8 cm (OR = 5.545, P = 0.010), and tumor number >3 (OR = 11.566, P = 0.007) were independent predictors of MVI. A scoring system was constructed, and the MVI rate was significantly higher in patients with a score of ≥3 than those with a score of <3 (64.1% vs. 10.9%, P < 0.001). Overall and recurrence-free survival rates were significantly lower in patients with a score of ≥3 (both P < 0.001). CONCLUSIONS Serum AFP level >400 μg/L, serum GGT level >130 U/L, total tumor diameter >8 cm, and tumor number >3 were preoperative predictors of MVI in patients with multinodular HCC. In patients with a high risk of MVI and well-preserved liver function, anatomic resection may be worth considering.
Collapse
|
|
41
|
Zhao G, Huang ZM, Kong YL, Wen DQ, Li Y, Ren L, Zhang HY. Cortactin is a sensitive biomarker relative to the poor prognosis of human hepatocellular carcinoma. World J Surg Oncol 2013; 11:74. [PMID: 23518204 PMCID: PMC3620941 DOI: 10.1186/1477-7819-11-74] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 03/10/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cortactin is an important regulator involved in invasion and migration of hepatocellular carcinoma (HCC). The aim of this study was to elucidate the forecasting role of cortactin in resectable HCCs. METHODS We compared the invasiveness and motility among liver epithelial cell line and HCC cell lines by using Transwell assay and wound healing assay. We further investigated the CTTN mRNA expression by real-time PCR. Next, 91 HCC and 20 normal liver tissue samples were detected by IHC and real-time PCR. Finally, we analyzed the clinicopathologic features and survival time of the HCC cases. RESULTS We identified that HepG2, LM3, and SK-Hep-1 had more invasiveness and motility (P <0.05). Compared with liver epithelial cell line, CTTN expression was higher in LM3, HepG2, and MHCC97-L (P <0.01) and lower in SK-Hep-1 (P <0.05). IHC examination showed cortactin expression was closely relative to TNM stage (AJCC/UICC), cancer embolus, and metastasis (P <0.01). Cortactin overexpression indicated a longer survival time of 52 ± 8.62 months and low expression of a shorter survival time of 20 ± 4.95 months (P <0.01). Cortactin examination has more predictive power in patients with Child-Pugh grade A and BCLC stage 0-B. CONCLUSIONS Overexpression of cortactin is closely associated with poor human HCCs prognosis that caused by cancer embolus and metastasis. Cortactin and CTTN should be used for differentiating varieties of survival for patients after HCC resection.
Collapse
Affiliation(s)
- Gang Zhao
- Department of Hepatobiliary Surgery, Chinese PLA Air Force General Hospital, No,30 Fucheng Road, Haidian District, Beijing 100142, China
| | | | | | | | | | | | | |
Collapse
|
|
42
|
Chen L, Zhang Q, Chang W, Du Y, Zhang H, Cao G. Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma. Eur J Cancer 2012; 48:1977-87. [DOI: 10.1016/j.ejca.2012.01.015] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Revised: 01/08/2012] [Accepted: 01/16/2012] [Indexed: 02/06/2023]
|