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Hitchcock CL, Chapman GJ, Mojzisik CM, Mueller JK, Martin EW. A Concept for Preoperative and Intraoperative Molecular Imaging and Detection for Assessing Extent of Disease of Solid Tumors. Oncol Rev 2024; 18:1409410. [PMID: 39119243 PMCID: PMC11306801 DOI: 10.3389/or.2024.1409410] [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: 03/30/2024] [Accepted: 05/28/2024] [Indexed: 08/10/2024] Open
Abstract
The authors propose a concept of "systems engineering," the approach to assessing the extent of diseased tissue (EODT) in solid tumors. We modeled the proof of this concept based on our clinical experience with colorectal carcinoma (CRC) and gastrinoma that included short and long-term survival data of CRC patients. This concept, applicable to various solid tumors, combines resources from surgery, nuclear medicine, radiology, pathology, and oncology needed for preoperative and intraoperative assessments of a patient's EODT. The concept begins with a patient presenting with biopsy-proven cancer. An appropriate preferential locator (PL) is a molecule that preferentially binds to a cancer-related molecular target (i.e., tumor marker) lacking in non-malignant tissue and is the essential element. Detecting the PL after an intravenous injection requires the PL labeling with an appropriate tracer radionuclide, a fluoroprobe, or both. Preoperative imaging of the tracer's signal requires molecular imaging modalities alone or in combination with computerized tomography (CT). These include positron emission tomography (PET), PET/CT, single-photon emission computed tomography (SPECT), SPECT/CT for preoperative imaging, gamma cameras for intraoperative imaging, and gamma-detecting probes for precise localization. Similarly, fluorescent-labeled PLs require appropriate cameras and probes. This approach provides the surgeon with real-time information needed for R0 resection.
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Affiliation(s)
- Charles L. Hitchcock
- Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, United States
- Actis Medical, LLC, Powell, OH, United States
| | - Gregg J. Chapman
- Actis Medical, LLC, Powell, OH, United States
- Department of Electrical and Computer Engineering, College of Engineering, The Ohio State University, Columbus, OH, United States
| | | | | | - Edward W. Martin
- Actis Medical, LLC, Powell, OH, United States
- Division of Surgical Oncology, Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, United States
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Li K, Meng M, Zhang W, Li J, Wang Y, Zhou C. Diagnostic value of one-step nucleic acid amplification for sentinel lymph node metastasis in cytokeratin 19-positive tumors: evidence from bioinformatics and meta-analysis. Front Oncol 2024; 14:1370709. [PMID: 38651158 PMCID: PMC11033366 DOI: 10.3389/fonc.2024.1370709] [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: 01/16/2024] [Accepted: 03/19/2024] [Indexed: 04/25/2024] Open
Abstract
Background The status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database. Methods Two researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection. Results After literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/μl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/μl. Discussion OSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.
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Affiliation(s)
- Ke Li
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, Shandong, China
| | - Min Meng
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, Shandong, China
| | - Weiwei Zhang
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, Shandong, China
| | - Junyi Li
- Department of Clinical Medicine, Shandong First Medical University, Jinan, Shandong, China
| | - Yiting Wang
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, Shandong, China
| | - Changhui Zhou
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, Shandong, China
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Saez de Gordoa K, Rodrigo-Calvo MT, Archilla I, Lopez-Prades S, Diaz A, Tarragona J, Machado I, Ruiz Martín J, Zaffalon D, Daca-Alvarez M, Pellisé M, Camps J, Cuatrecasas M. Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study. Cancers (Basel) 2023; 15:5481. [PMID: 38001742 PMCID: PMC10670609 DOI: 10.3390/cancers15225481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/11/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.
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Affiliation(s)
- Karmele Saez de Gordoa
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Maria Teresa Rodrigo-Calvo
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Ivan Archilla
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Sandra Lopez-Prades
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Alba Diaz
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
| | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, 25198 Lleida, Spain;
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncología, Hospital Quirón-Salud Valencia, University of Valencia, 46010 Valencia, Spain;
- Centro de Investigación Biomédica en Red en Cancer (CIBERONC), 28029 Madrid, Spain
| | - Juan Ruiz Martín
- Pathology Department, Virgen de la Salud Hospital, 45071 Toledo, Spain;
| | - Diana Zaffalon
- Gastroenterology Department, Consorci Sanitari de Terrassa, 08227 Terrassa, Spain;
| | - Maria Daca-Alvarez
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Maria Pellisé
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Jordi Camps
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Cell Biology and Medical Genetics Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Autonomous University of Barcelona (UAB), 08193 Bellaterra, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
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Crafa F, Vanella S, Morante A, Catalano OA, Pomykala KL, Baiamonte M, Godas M, Antunes A, Costa Pereira J, Giaccaglia V. Non-exposed endoscopic wall-inversion surgery with one-step nucleic acid amplification for early gastrointestinal tumors: Personal experience and literature review. World J Gastroenterol 2023; 29:3883-3898. [PMID: 37426319 PMCID: PMC10324533 DOI: 10.3748/wjg.v29.i24.3883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/11/2023] [Accepted: 05/31/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Laparoscopic and endoscopic cooperative surgery is a safe, organ-sparing surgery that achieves full-thickness resection with adequate margins. Recent studies have demonstrated the safety and efficacy of these procedures. However, these techniques are limited by the exposure of the tumor and mucosa to the peritoneal cavity, which could lead to viable cancer cell seeding and the spillage of gastric juice or enteric liquids into the peritoneal cavity. Non-exposed endoscopic wall-inversion surgery (NEWS) is highly accurate in determining the resection margins to prevent intraperitoneal contamination because the tumor is inverted into the visceral lumen instead of the peritoneal cavity. Accurate intraoperative assessment of the nodal status could allow stratification of the extent of resection. One-step nucleic acid amplification (OSNA) can provide a rapid method of evaluating nodal tissue, whilst near-infrared laparoscopy together with indocyanine green can identify relevant nodal tissue intraoperatively.
AIM To determine the safety and feasibility of NEWS in early gastric and colon cancers and of adding rapid intraoperative lymph node (LN) assessment with OSNA.
METHODS The patient-based experiential portion of our investigations was conducted at the General and Oncological Surgery Unit of the St. Giuseppe Moscati Hospital (Avellino, Italy). Patients with early-stage gastric or colon cancer (diagnosed via endoscopy, endoscopic ultrasound, and computed tomography) were included. All lesions were treated by NEWS procedure with intraoperative OSNA assay between January 2022 and October 2022. LNs were examined intraoperatively with OSNA and postoperatively with conventional histology. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. Data were collected prospectively and analyzed retrospectively.
RESULTS A total of 10 patients (5 males and 5 females) with an average age of 70.4 ± 4.5 years (range: 62-78 years) were enrolled in this study. Five patients were diagnosed with gastric cancer. The remaining 5 patients were diagnosed with early-stage colon cancer. The mean tumor diameter was 23.8 ± 11.6 mm (range: 15-36 mm). The NEWS procedure was successful in all cases. The mean procedure time was 111.5 ± 10.7 min (range: 80-145 min). The OSNA assay revealed no LN metastases in any patients. Histologically complete resection (R0) was achieved in 9 patients (90.0%). There was no recurrence during the follow-up period.
CONCLUSION NEWS combined with sentinel LN biopsy and OSNA assay is an effective and safe technique for the removal of selected early gastric and colon cancers in which it is not possible to adopt conventional endoscopic resection techniques. This procedure allows clinicians to acquire additional information on the LN status intraoperatively.
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Affiliation(s)
- Francesco Crafa
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Serafino Vanella
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Aristide Morante
- Division of Gastorenterology and Endoscopy, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Onofrio A Catalano
- Department of Radiology, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Kelsey L Pomykala
- Department of Nuclear Medicine, Department of Radiological Sciences, University Hospital Essen, University of Duisburg-Essen, Essen 45141, Germany
| | - Mario Baiamonte
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Maria Godas
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Alexandra Antunes
- Department of General Surgery, Braga Hospital, Braga 4710-243, Portugal
| | | | - Valentina Giaccaglia
- Department of Surgery, Medclinic City Hospital, Dubai 505004, United Arab Emirates
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Molecular Detection of Lymph Node Metastases in Lung Cancer Patients Using the One-Step Nucleic Acid Amplification Method:Clinical Significance and Prognostic Value. Cells 2022; 11:cells11244010. [PMID: 36552774 PMCID: PMC9776771 DOI: 10.3390/cells11244010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/01/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
The one-step nucleic acid amplification (OSNA) method allows for the quantitative evaluation of the tumor burden in resected lymph nodes (LNs) in patients with lung cancer. This technique enables to detect macro and micrometastases, facilitating the correct classification of patients for appropriate follow-up of the disease after surgery. Of 160 patients with resectable lung cancer whose LNs were examined by OSNA, H&E and CK19 IHC between July 2015 and December 2018, 110 patients with clinical stages from IA1 to IIIB were selected for follow-up. LN staging in lung cancer by pathological study led to understaging in 13.64% of the cases studied. OSNA allowed to quantify the tumor burden and establish a prognostic value. Patients with a total tumor load of ≥1650 cCP/uL were associated with a significantly increased likelihood of recurrence. Moreover, the survival of patients with <4405 cCP/uL was significantly higher than patients with ≥4405 cCP/uL. The OSNA assay is a rapid and accurate technique for quantifying the tumor burden in the LNs of lung cancer patients and OSNA quantitative data could allow to establish prognostic values for recurrence-free survival and overall survival in this type of malignancy.
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Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage-A Multicentre Study. Cancers (Basel) 2022; 14:cancers14246072. [PMID: 36551559 PMCID: PMC9775901 DOI: 10.3390/cancers14246072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients.
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Algara M, Rodríguez E, Martínez-Arcelus FJ, Salinas J, Sanz X, Beato I, Manso A, Soler A, Rodríguez JR, Frías A, Calín A, Juan G, Meireles P, Flaquer A. OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial. Radiother Oncol 2022; 176:76-82. [PMID: 36210628 DOI: 10.1016/j.radonc.2022.09.006] [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: 03/01/2022] [Revised: 09/06/2022] [Accepted: 09/11/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND PURPOSE In breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. MATERIALS AND METHODS BC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250-15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). RESULTS Five-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI < 5.7%]; non-inferiority p = 0.075). Cumulative Incidences of LRR were 3.5% (INC) and 3.4% (INT) (difference of 0.1% [<4.8%]; p = 0.021), and 5% (INC) and 3.5% (INT) (difference 1.4% [<6.0%]; non-inferiority p = 0.101) for DR. CT was more Incident with INT (26.9%) than with INC (19.2%), though the difference was not statistically significant (HR 1.39 [95% CI: 0.92, 2.10]; p = 0.11). CONCLUSION Intentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR. REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT02335957.
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Affiliation(s)
- Manuel Algara
- Radiation Oncology Department, Del Mar Hospital, Passeig Maritim 25, 08003 Barcelona, Spain.
| | - Elvira Rodríguez
- Radiation Oncology Department, Virgen del Rocío University Hospital, Av. Manuel Siurot, S/n, 41013 Sevilla, Spain.
| | - Francisco José Martínez-Arcelus
- Radiation Oncology Department, La Fe Polytechnic University Hospital, Av. Fernando Abril Martorell, 106, 46026 Valencia, Spain.
| | - Juan Salinas
- Radiation Oncology Department, Santa Lucia General University Hospital, C. Minarete, s/n, 30202 Cartagena, Spain.
| | - Xavier Sanz
- Radiation Oncology Department, Del Mar Hospital, Passeig Maritim 25, 08003 Barcelona, Spain.
| | - Inmaculada Beato
- Radiation Oncology Department, Castellón Provincial Hospital, Av. del Dr. Clarà, 19, 12002 Castellón de La Plana, Spain.
| | - Aurea Manso
- Radiation Oncology Department, La Paz University Hospital, P.° de la Castellana, 261, 28046 Madrid, Spain.
| | - Ana Soler
- Radiation Oncology Department, De La Ribera Hospital, km 1, Ctra. Corbera, 46600 Alzira, Spain.
| | - José Reyes Rodríguez
- Radiation Oncology Department, University Hospital of Leon, C. Altos de Nava, s/n, 24071 León, Spain.
| | - Andere Frías
- Radiation Oncology Department, de Cruces University Hospital, Plaza de Cruces, 48903 Barakaldo, Spain.
| | - Ana Calín
- Radiation Oncology Department, Gregorio Marañón University General Hospital, C. Dr. Esquerdo, 46, 28007 Madrid, Spain.
| | - Germán Juan
- Radiation Oncology Department, Cabueñes University Hospital, Los Prados, 395, 33394 Gijón, Spain.
| | - Pedro Meireles
- Radiation Oncology Department, São João Universitary Hospital Center, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
| | - Amanda Flaquer
- Radiation Oncology Department, Araba Txagorritxu University Hospital, Jose Atxotegi Kalea, s/n, 01009 Gasteiz, Spain.
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Crafa F, Vanella S, Catalano OA, Pomykala KL, Baiamonte M. Role of one-step nucleic acid amplification in colorectal cancer lymph node metastases detection. World J Gastroenterol 2022; 28:4019-4043. [PMID: 36157105 PMCID: PMC9403438 DOI: 10.3748/wjg.v28.i30.4019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/03/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
Current histopathological staging procedures in colorectal cancer (CRC) depend on midline division of the lymph nodes (LNs) with one section of hematoxylin and eosin staining. Cancer cells outside this transection line may be missed, which could lead to understaging of Union for International Cancer Control Stage II high-risk patients. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid molecular diagnostic tool for LN metastases detection. It is a molecular technique that can analyze the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumor-specific cytokeratin 19 mRNA. Our findings suggest that the OSNA assay has a high diagnostic accuracy in detecting metastatic LNs in CRC and a high negative predictive value. OSNA is a standardized, observer-independent technique, which may lead to more accurate staging. It has been suggested that in stage II CRC, the upstaging can reach 25% and these patients can access postoperative adjuvant chemotherapy. Moreover, intraoperative OSNA sentinel node evaluation may allow early CRC to be treated with organ-preserving surgery, while in more advanced-stage disease, a tailored lymphadenectomy can be performed considering the presence of aberrant lymphatic drainage and skip metastases.
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Affiliation(s)
- Francesco Crafa
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Serafino Vanella
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Onofrio A Catalano
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Kelsey L Pomykala
- Department of Nuclear Medicine, Department of Radiological Sciences, David Geffen School of Medicine at University of California, Los Angeles, University Hospital Essen, University of Duisburg-Essen, Essen 45141, Germany
| | - Mario Baiamonte
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
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One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study. Sci Rep 2022; 12:7297. [PMID: 35508484 PMCID: PMC9068616 DOI: 10.1038/s41598-022-11064-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/01/2022] [Indexed: 11/24/2022] Open
Abstract
One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.
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Application of One-Step Nucleic Acid Amplification (OSNA) in different cancer entities and usefulness in prostate cancer: a systematic review. BMC Cancer 2022; 22:357. [PMID: 35366849 PMCID: PMC8976947 DOI: 10.1186/s12885-022-09355-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 01/28/2022] [Indexed: 12/24/2022] Open
Abstract
Background Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies. Methods To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time. Results Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques. Conclusion OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis.
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11
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Detection of lymph node metastasis in non-small cell lung cancer using the new system of one-step nucleic acid amplification assay. PLoS One 2022; 17:e0265603. [PMID: 35312731 PMCID: PMC8936453 DOI: 10.1371/journal.pone.0265603] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 03/06/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system. Materials and methods 199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology. Results Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively. Conclusion The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively.
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12
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Hitchcock CL, Povoski SP, Mojzisik CM, Martin EW. Survival Advantage Following TAG-72 Antigen-Directed Cancer Surgery in Patients With Colorectal Carcinoma: Proposed Mechanisms of Action. Front Oncol 2021; 11:731350. [PMID: 34950576 PMCID: PMC8688248 DOI: 10.3389/fonc.2021.731350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 10/25/2021] [Indexed: 12/09/2022] Open
Abstract
Patients with colorectal carcinoma (CRC) continue to have variable clinical outcomes despite undergoing the same surgical procedure with curative intent and having the same pathologic and clinical stage. This problem suggests the need for better techniques to assess the extent of disease during surgery. We began to address this problem 35 years ago by injecting patients with either primary or recurrent CRC with 125I-labeled murine monoclonal antibodies against the tumor-associated glycoprotein-72 (TAG-72) and using a handheld gamma-detecting probe (HGDP) for intraoperative detection and removal of radioactive, i.e., TAG-72-positive, tissue. Data from these studies demonstrated a significant difference in overall survival data (p < 0.005 or better) when no TAG-72-positive tissue remained compared to when TAG-72-positive tissue remained at the completion of surgery. Recent publications indicate that aberrant glycosylation of mucins and their critical role in suppressing tumor-associated immune response help to explain the cellular mechanisms underlying our results. We propose that monoclonal antibodies to TAG-72 recognize and bind to antigenic epitopes on mucins that suppress the tumor-associated immune response in both the tumor and tumor-draining lymph nodes. Complete surgical removal of all TAG-72-positive tissue serves to reverse the escape phase of immunoediting, allowing a resetting of this response that leads to improved overall survival of the patients with either primary or recurrent CRC. Thus, the status of TAG-72 positivity after resection has a significant impact on patient survival.
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Affiliation(s)
- Charles L. Hitchcock
- Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, United States
| | - Stephen P. Povoski
- Division of Surgical Oncology, Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, United States
| | - Cathy M. Mojzisik
- Division of Surgical Oncology, Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, United States
| | - Edward W. Martin
- Division of Surgical Oncology, Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, United States
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13
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Numata M, Shiozawa M, Godai T, Kazama K, Okamoto H, Kato A, Katayama Y, Sato S, Sugano N, Kohmura T, Higuchi A, Saito K, Iguchi K, Atsumi Y, Aoyama T, Tamagawa H, Mushiake H, Saeki H, Yukawa N, Taguri M, Sato M, Rino Y. Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801). J Surg Oncol 2021; 125:457-464. [PMID: 34704609 DOI: 10.1002/jso.26730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/19/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVES Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.
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Affiliation(s)
- Masakatsu Numata
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Manabu Shiozawa
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Teni Godai
- Department of Surgery, Fujisawa Shonandai Hospital, Fujisawa, Kanagawa, Japan
| | - Keisuke Kazama
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Hironao Okamoto
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Aya Kato
- Department of Surgery, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan
| | - Yusuke Katayama
- Department of Surgery, Hadano Red Cross Hospital, Hadano, Kanagawa, Japan
| | - Sumito Sato
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Nobuhiro Sugano
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Takashi Kohmura
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Akio Higuchi
- Department of Surgery, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan
| | - Kentaro Saito
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Kenta Iguchi
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Yosuke Atsumi
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Hiroyuki Mushiake
- Department of Surgery, Saiseikai Yokohama Nanbu Hospital, Yokohama, Kanagawa, Japan
| | - Hiroyuki Saeki
- Department of Surgery, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Maho Sato
- Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
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Martínez-López E, Martínez-Pérez A, Navarro-Martínez S, Sebastián-Tomás JC, de'Angelis N, García-Granero E. Real-time fluorescence image-guided gastrointestinal oncologic surgery: Towards a new era. World J Gastrointest Oncol 2021; 13:1029-1042. [PMID: 34616510 PMCID: PMC8465438 DOI: 10.4251/wjgo.v13.i9.1029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/14/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Technological improvements are crucial in the evolution of surgery. Real-time fluorescence-guided surgery (FGS) has spread worldwide, mainly because of its usefulness during the intraoperative decision-making processes. The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes. FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections. Therefore, a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures. Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery, the technique is currently applied in gastric or splenic flexure cancers, as they both present complex and variable lymphatic drainages. FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies. New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins. The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery. We put a special focus on the different applications of FGS, discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.
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Affiliation(s)
- Elías Martínez-López
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Aleix Martínez-Pérez
- Faculty of Health Sciences, Valencian International University, Valencia 46002, Spain
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Sergio Navarro-Martínez
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Juan Carlos Sebastián-Tomás
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Nicola de'Angelis
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Eduardo García-Granero
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario y Politécnico La Fe, Valencia 46026, Spain
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15
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Tani K, Itabashi M, Okuya K, Okita K, Takemasa I, Tomita N, Ogawa S, Nagashima Y, Yamamoto M. Feasibility of Pooled One-Step Nucleic Acid Amplification for Molecular Staging of Pathologically Node-Negative Colon Cancer: A Prospective Multicenter Study. Ann Surg Oncol 2021; 28:8804-8812. [PMID: 34086123 DOI: 10.1245/s10434-021-10140-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 04/30/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND Although conventional one-step nucleic acid amplification (OSNA) is a useful molecular-staging method, its complexity hinders its use in clinical practice. A pooled approach for OSNA (pOSNA) has been evaluated for its feasibility in pathologically node-negative colon cancer (pNNCC) for molecular staging of lymph node metastasis in clinical practice. METHODS Subjects were patients diagnosed with clinical stage II-IIIA colon cancer between January 2017 and September 2018. pOSNA involved harvesting pericolic lymph nodes from fresh surgical specimens, cutting them in half, placing 50% of the nodes in a single test tube, and performing the OSNA assay. The remaining halved pericolic, intermediate, and main lymph nodes were submitted for histopathologic examination, with metastasis determined by hematoxylin and eosin staining of a cut surface of each node. RESULTS Of the 98 enrolled patients, 92 formed the analysis set. The mean number of harvested lymph nodes per case was 24.3 (range 5-66) and the mean number of lymph nodes used for pOSNA analysis was 6.9 (range 1-35). The concordance rate, sensitivity, and specificity between methods were 89.1%, 84.6% (95% confidence interval [CI] 0.80-0.91), and 90.9% (95% CI 0.88-0.94), respectively. The pOSNA upstaging rate for node-negative patients was 9.1% (6/66), and pOSNA returned false-negative results in 15.4% of node-positive cases (4/26). CONCLUSIONS pOSNA demonstrated an upstaging rate for pNNCC equivalent to that in previous studies, suggesting its feasibility for molecular staging of pNNCC in clinical practice.
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Affiliation(s)
- Kimitaka Tani
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Michio Itabashi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
| | - Koichi Okuya
- Department of Surgery, Surgical Oncology, and Science, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Kenji Okita
- Department of Surgery, Surgical Oncology, and Science, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology, and Science, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Naohiro Tomita
- Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.,Cancer Treatment Center, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Shimpei Ogawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Yoji Nagashima
- Department of Surgical Pathology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
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16
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Archilla I, Díaz-Mercedes S, Aguirre JJ, Tarragona J, Machado I, Rodrigo MT, Lopez-Prades S, Gorostiaga I, Landolfi S, Alén BO, Balaguer F, Castells A, Camps J, Cuatrecasas M. Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma? Clin Transl Gastroenterol 2021; 12:e00303. [PMID: 33939382 PMCID: PMC7909319 DOI: 10.14309/ctg.0000000000000303] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 12/18/2020] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC. METHODS In this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry. RESULTS One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001). DISCUSSION The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).
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Affiliation(s)
- Ivan Archilla
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Sherley Díaz-Mercedes
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | | | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncologia and Hospital QuironSalud, Valencia, Spain
| | - Maria Teresa Rodrigo
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Sandra Lopez-Prades
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Iñigo Gorostiaga
- Pathology Department, Arava University Hospital, Vitoria-Gasteiz, Spain
| | - Stefania Landolfi
- Pathology Department, Vall Hebron University Hospital, Barcelona, Spain
| | - Begoña Otero Alén
- Molecular Pathology Division, Pathology Department, CHUAC/INIBIC, A Coruña, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Jordi Camps
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Miriam Cuatrecasas
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
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17
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Weixler B, Teixeira da Cunha S, Warschkow R, Demartines N, Güller U, Zettl A, Vahrmeijer A, van de Velde CJH, Viehl CT, Zuber M. Molecular Lymph Node Staging with One-Step Nucleic Acid Amplification and its Prognostic Value for Patients with Colon Cancer: The First Follow-up Study. World J Surg 2021; 45:1526-1536. [PMID: 33512566 PMCID: PMC8026461 DOI: 10.1007/s00268-020-05949-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 01/11/2023]
Abstract
Background Molecular lymph node workup with one-step nucleic acid amplification (OSNA) is a validated diagnostic adjunct in breast cancer and also appealing for colon cancer (CC) staging. This study, for the first time, evaluates the prognostic value of OSNA in CC. Patients and methods The retrospective study includes patients with stage I-III CC from three centres. Lymph nodes were investigated with haematoxylin and eosin (H&E) and with OSNA, applying a 250 copies/μL threshold of CK19 mRNA. Diagnostic value of H&E and OSNA was assessed by survival analysis, sensitivity, specificity and time-dependent receiver operating characteristic curves. Results Eighty-seven patients were included [mean follow-up 53.4 months (± 24.9)]. Disease recurrence occurred in 16.1% after 19.8 months (± 12.3). Staging with H&E independently predicted worse cancer-specific survival in multivariate analysis (HR = 10.77, 95% CI 1.07–108.7, p = 0.019) but not OSNA (HR = 3.08, 95% CI 0.26–36.07, p = 0.197). With cancer-specific death or recurrence as gold standard, H&E sensitivity was 46.7% (95% CI 21.3–73.4%) and specificity 84.7% (95% CI 74.3–92.1%). OSNA sensitivity and specificity were 60.0% (95% CI 32.3–83.7%) and 75.0% (95% CI 63.4–84.5%), respectively. Conclusions In patients with CC, OSNA does not add relevant prognostic value to conventional H&E contrasting findings in other cancers. Further studies should assess lower thresholds for OSNA (< 250 copies/μL).
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.,Department of General, Visceral and Vascular Surgery, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany
| | | | - René Warschkow
- Department of Surgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Nicolas Demartines
- Department of Surgery, Vaudois University Hospital Centre, Lausanne, Switzerland
| | - Ulrich Güller
- Department of Oncology, Spital STS AG, Thun, Switzerland
| | - Andreas Zettl
- Department of Pathology, Viollier AG, Basel, Switzerland
| | - Alexander Vahrmeijer
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Carsten T Viehl
- Department of Surgery, Hospital Centre Biel, Biel, Switzerland
| | - Markus Zuber
- Department of Surgery, Cantonal Hospital Olten, Olten, Switzerland. .,Visceral Surgery Centre Clarunis, St. Clara Hospital and University Hospital Basel, University of Basel, Spitalstrasse 21, CH-4031, Basel, Switzerland.
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18
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Hiyoshi Y, Akiyoshi T, Fukunaga Y. The advantage of one-step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients. Ann Gastroenterol Surg 2021; 5:60-66. [PMID: 33532681 PMCID: PMC7832960 DOI: 10.1002/ags3.12392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/28/2020] [Accepted: 08/01/2020] [Indexed: 12/20/2022] Open
Abstract
Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)-stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time-consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one-step nucleic acid amplification (OSNA), is a rapid and semi-quantitative examination quantifying the number of cytokeratin 19 (CK-19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node-negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.
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Affiliation(s)
- Yukiharu Hiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Takashi Akiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Yosuke Fukunaga
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
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19
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Evaluation of the prognostic relevance of the recommended minimum number of lymph nodes in colorectal cancer-a propensity score analysis. Int J Colorectal Dis 2021; 36:779-789. [PMID: 33454816 PMCID: PMC7952332 DOI: 10.1007/s00384-021-03835-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/05/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE Nodal status in colorectal cancer (CRC) is an important prognostic factor, and adequate lymph node (LN) staging is crucial. Whether the number of resected and analysed LN has a direct impact on overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) is much discussed. Guidelines request a minimum number of 12 LN to be analysed. Whether that threshold marks a prognostic relevant cut-off remains unknown. METHODS Patients operated for stage I-III CRC were identified from a prospectively maintained database. The impact of the number of analysed LN on OS, CSS and DFS was assessed using Cox regression and propensity score analysis. RESULTS Of the 687 patients, 81.8% had ≥ 12 LN resected and analysed. Median LN yield was 17.0 (IQR 13.0-23.0). Resection and analysis of ≥ 12 LN was associated with improved OS (HR = 0.73, 95% CI: 0.56-0.95, p = 0.033), CSS (HR 0.52, 95% CI: 0.31-0.85, p = 0.030) and DFS (HR = 0.73, 95% CI: 0.57-0.95, p = 0.030) in multivariate Cox analysis. After adjusting for biasing factors with propensity score matching, resection of ≥ 12 LN was significantly associated with improved OS (HR = 0.59; 95% CI: 0.43-0.81; p = 0.002), CSS (HR = 0.34; 95% CI: 0.20-0.60; p < 0.001) and DFS (HR = 0.55; 95% CI: 0.41-0.74; p < 0.001) compared to patients with < 12 LN. CONCLUSION Eliminating biasing factors by a propensity score matching analysis underlines the prognostic importance of the number of analysed LN. The set threshold marks the minimum number of required LN but nevertheless represents a cut-off regarding outcome in stage I-III CRC. This analysis therefore highlights the significance and importance of adherence to surgical oncological standards.
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The evolving role of one-step nucleic acid amplification (OSNA) for the intra-operative detection of lymph node metastases: A diagnostic accuracy meta-analysis. Eur J Surg Oncol 2020; 47:1233-1243. [PMID: 33309549 DOI: 10.1016/j.ejso.2020.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/21/2020] [Accepted: 12/01/2020] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND One Step Nucleic Acid Amplification (OSNA) assay has recently emerged as a rapid molecular diagnostic tool for the detection of lymph node (LN) metastases. It is a molecular technique that analyses the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumour specific cytoceratin 19 mRNA. AIM To ascertain the diagnostic accuracy of OSNA assay in detecting LN metastases amongst different types of malignancy. DESIGN We systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2020. Quality assessment was performed using the Modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We calculated pooled diagnostic indices using the random-effects model. Meta-regression and sub-group analyses were performed to address heterogeneity. RESULTS 31 studies were included in this meta-analysis, including four different types of cancer. The risk of bias and the overall quality of included studies was moderate to high. There was no evidence of publication bias. The pooled diagnostic odds ratio (DOR) for detecting LN metastases in gynaecological, head & neck/thyroid, gastrointestinal and lung cancer were 100.38, 76.17, 275.14, and 305.84, respectively. CONCLUSIONS Our findings suggest that OSNA assay had a high diagnostic accuracy in detecting metastatic LNs in different types of malignancy. This evidence is constrained by the limited studies available for few tumour types and the rather high heterogeneity for few outcomes.
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Prognostic Significance of Lymph Node Examination by the OSNA Method in Lung Cancer Patients-Comparison with the Standard Histopathological Procedure. Cells 2020; 9:cells9122611. [PMID: 33291819 PMCID: PMC7762050 DOI: 10.3390/cells9122611] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/26/2020] [Accepted: 12/01/2020] [Indexed: 12/25/2022] Open
Abstract
The aim of the study was to compare the prognostic significance of lymph node status of patients with lung cancer analyzed by three different methods: hematoxylin and eosin (H&E), immunohistochemistry of cytokeratin 19 (IHC CK19), and One-Step Nucleic Acid Amplification (OSNA). The clinical relevance of the results was evaluated based on relation to prognosis; the disease-free interval (DFI) and overall survival (OS) were analyzed. During radical surgical treatment, a total of 1426 lymph nodes were obtained from 100 patients, creating 472 groups of nodes (4–5 groups per patient) and examined by H&E, IHC CK19 and OSNA. The median follow-up was 44 months. Concordant results on the lymph node status of the H&E, IHC CK19 and OSNA examinations were reported in 78% of patients. We recorded shorter OS in patients with positive results provided by both OSNA and H&E. The study demonstrated a higher percentage of detected micrometastases in lymph nodes by the OSNA method. However, the higher sensitivity of the OSNA, with the cut-off value 250 copies of mRNA of CK19/µL, resulted in a lower association of OSNA positivity with progress of the disease compared to H&E. Increasing the cut-off to 615 copies resulted in an increase in concordance between the OSNA and H&E, which means that the higher cut-off is more relevant in the case of lung tumors.
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Bizzarri N, Pedone Anchora L, Zannoni GF, Santoro A, Valente M, Inzani F, Gallotta V, Conte C, Chiantera V, Fanfani F, Fagotti A, Ferrandina G, Scambia G. Role of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node low-volume metastasis in early-stage cervical cancer. Int J Gynecol Cancer 2020; 30:364-371. [PMID: 31980488 DOI: 10.1136/ijgc-2019-000939] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/27/2019] [Accepted: 01/06/2020] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Growing evidence in the literature supports the accuracy of sentinel lymph node (SLN) biopsy in early-stage cervical cancer. One-step nucleic acid amplification (OSNA) is a rapid assay able to detect cytokeratin 19-mRNA in SLNs, and it can be used for intra-operative detection of low-volume metastases. The aim of this study was to evaluate the rate of low-volume metastasis in SLNs detected by OSNA in patients with early-stage cervical cancer. Secondary aims were to define the sensitivity and the negative predictive value of SLN biopsy assessed with OSNA. METHODS After IRB approval, consecutive patients who underwent surgery for International Federation of Gynecology and Obstetrics stage IA1 with lymph-vascular space involvement to IB1 between November 2017 and July 2019 and had SLN biopsy and pelvic lymphadenectomy were included. SLNs were detected with indocyanine-green cervical injection and sent intra-operatively for OSNA. RESULTS Eighteen patients underwent SLN assessment with OSNA and systematic pelvic lymphadenectomy in the study period. Four (22.2%) patients had unilateral and 14 (77.8%) had bilateral mapping. OSNA detected micro-metastasis in 6/18 (33.3%) patients. All micro-metastases were detected in patients with bilateral SLN mapping. The sensitivity and negative predictive value of SLN in detecting lymph node metastasis with OSNA calculated per pelvic sidewall were 85.7% and 96.1%, respectively. The false negative rate in mapped sidewalls was 14.3%. DISCUSSION This is the first series entirely processing SLNs for OSNA in early-stage cervical cancer. OSNA is able to intra-operatively detect low-volume metastases in SLNs. Further studies are necessary to confirm the accuracy of this technique and to assess survival implications of low-volume metastases detected by OSNA.
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Affiliation(s)
- Nicolò Bizzarri
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
| | - Luigi Pedone Anchora
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
| | - Gian Franco Zannoni
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Angela Santoro
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Michele Valente
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Frediano Inzani
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Valerio Gallotta
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
| | - Carmine Conte
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
| | - Vito Chiantera
- Department of Gynecologic Oncology, ARNAS Civico Di Cristina Benfratelli, Università di Palermo, Palermo, Italy
| | - Francesco Fanfani
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Anna Fagotti
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Gabriella Ferrandina
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
| | - Giovanni Scambia
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy
- Università Cattolica del Sacro Cuore, Istituto di Ginecologia e Ostetricia, Roma, Italia, Rome, Italy
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Itabashi M, Yamamoto H, Tomita N, Inomata M, Murata K, Hayashi S, Miyake Y, Igarashi S, Kato T, Noura S, Furuhata T, Ozawa H, Takemasa I, Yasui M, Takeyama H, Okamura S, Ohno Y, Matsuura N. Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study. Ann Surg Oncol 2019; 27:1077-1083. [PMID: 31722072 PMCID: PMC7060165 DOI: 10.1245/s10434-019-07971-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Indexed: 01/11/2023]
Abstract
Background For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. Methods We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. Results Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). Conclusions This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC. Electronic supplementary material The online version of this article (10.1245/s10434-019-07971-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Michio Itabashi
- Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku, Japan
| | - Hirofumi Yamamoto
- Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan.
| | - Naohiro Tomita
- Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Kohei Murata
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Shigeoki Hayashi
- Department of Digestive Surgery, Nihon University Hospital, Chiyoda, Japan
| | - Yasuhiro Miyake
- Department of Surgery, Osaka Minato Central Hospital, Osaka, Japan
| | - Seiji Igarashi
- Division of Pathology, Tsuboi Cancer Center Hospital, Koriyama, Japan
| | - Takeshi Kato
- Department of Colorectal Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Shingo Noura
- Department of Surgery, Osaka Rosai Hospital, Sakai, Japan
| | - Tomohisa Furuhata
- Division of Gastroenterological and General Surgery, St. Marianna University Toyoko Hospital, Kawasaki, Japan
| | - Heita Ozawa
- Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | | | - Shu Okamura
- Department of Surgery, Suita Municipal Hospital, Suita, Japan
| | - Yuko Ohno
- Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, Suita, Japan
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Medas F, Coni P, Podda F, Salaris C, Cappellacci F, Faa G, Calò PG. Evaluation of accuracy of one-step nucleic acid amplification (OSNA) in diagnosis of lymph node metastases of papillary thyroid carcinoma. Diagnostic study. Ann Med Surg (Lond) 2019; 46:17-22. [PMID: 31485327 PMCID: PMC6717061 DOI: 10.1016/j.amsu.2019.08.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 08/13/2019] [Accepted: 08/17/2019] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets resistance due to the high incidence of postoperative complications. Recently, new molecular biologic techniques, such as One Step Nucleic Acid Amplification (OSNA), have spread widely, allowing to quickly isolate, amplify and quantify mRNA encoding for proteins selectively present in neoplastic cells, as Cytokeratine-19. The aim of this study is to evaluate the application of OSNA to intraoperative diagnosis of node metastases of PTC. METHODS We included in the study patients with preoperative diagnosis of PTC; from each patient one or more lymph nodes were collected. To assess OSNA accuracy, each lymph node was divided into two halves: the first one was analysed with histopathological and immunohistochemical examination, whereas the second was studied with OSNA. RESULTS Twenty-six lymph nodes from 13 patients were included in the study. Overall, OSNA sensitivity was 87.5%, specificity 94.4%, positive predictive value 87.5%, negative predictive value 94.4% and accuracy 92.8%. DISCUSSION AND CONCLUSION OSNA is effective in detecting lymph node metastases of PTC. Considering the high risk of complications in CLND, and the uncertain prognostic value of lymph node metastases of PTC, OSNA seems to be a promising tool to identify intraoperatively patients who may benefit from CLND.
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Affiliation(s)
- Fabio Medas
- Department of Surgical Sciences, University of Cagliari, Cittadella Universitaria, SS554, Bivio Sestu, 09042, Monserrato, Italy
| | - Pierpaolo Coni
- Division of Pathological, University of Cagliari, Cagliari, Italy
| | - Francesco Podda
- Department of Surgical Sciences, University of Cagliari, Cittadella Universitaria, SS554, Bivio Sestu, 09042, Monserrato, Italy
| | - Claudia Salaris
- Department of Surgical Sciences, University of Cagliari, Cittadella Universitaria, SS554, Bivio Sestu, 09042, Monserrato, Italy
| | - Federico Cappellacci
- Department of Surgical Sciences, University of Cagliari, Cittadella Universitaria, SS554, Bivio Sestu, 09042, Monserrato, Italy
| | - Gavino Faa
- Division of Pathological, University of Cagliari, Cagliari, Italy
| | - Pietro Giorgio Calò
- Department of Surgical Sciences, University of Cagliari, Cittadella Universitaria, SS554, Bivio Sestu, 09042, Monserrato, Italy
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Escalante Pérez M, Hermida Romero MT, Otero Alén B, Álvarez Martínez M, Fernández Prado R, de la Torre Bravos M, Concha López Á. Detection of lymph node metastasis in lung cancer patients using a one-step nucleic acid amplification assay: a single-centre prospective study. J Transl Med 2019; 17:233. [PMID: 31331335 PMCID: PMC6647159 DOI: 10.1186/s12967-019-1974-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 07/05/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The use of one-step nucleic acid amplification (OSNA) allows for lymph node (LN) metastasis to be detected rapidly and accurately. We conducted a prospective single-centre clinical trial to evaluate OSNA assay in detecting LN metastasis of lung cancer. PATIENTS AND METHODS A total of 705 LNs from 160 patients with clinical stage IA to IVA lung cancer were included in this study. The LNs were divided and submitted to routine histological diagnosis and OSNA assay and the results were compared. We also examined keratin 19 expression of different histological types lung primary tumours. RESULTS When the cut-off value was set to 250 copies/µl, the concordance rate between the two methods was 96.17% and the sensitivity 97.14%. Discordant results were observed in 27 LNs of 21 patients. Most of these discordant results were molecular micrometastasis expressing a very low number of copies with negative histology. Most thoracic tumours were positive for keratin 19. CONCLUSIONS Our data show that the OSNA assay might be a useful and sensitive method to diagnose LN metastasis in lung cancer and could be applied to intraoperative decision-making in personalised lung cancer surgery based on LN status and a more accurate staging of patients.
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Affiliation(s)
- María Escalante Pérez
- Biobank of A Coruña, INIBIC, A Coruña, Spain. .,Molecular Biology Area, Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain.
| | - María Teresa Hermida Romero
- Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain
| | - Begoña Otero Alén
- Molecular Biology Area, Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain. .,Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain.
| | - Mónica Álvarez Martínez
- Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain
| | | | | | - Ángel Concha López
- Biobank of A Coruña, INIBIC, A Coruña, Spain.,Molecular Biology Area, Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain.,Department of Anatomical Pathology, University Hospital Complex A Coruña, As Xubias 84, 15006, A Coruña, Spain
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Performance of a new system using a one-step nucleic acid amplification assay for detecting lymph node metastases in breast cancer. Med Oncol 2019; 36:54. [DOI: 10.1007/s12032-019-1277-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 04/26/2019] [Indexed: 11/25/2022]
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Bhalla A, Zulfiqar M, Bluth MH. Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018. Clin Lab Med 2019; 38:311-342. [PMID: 29776633 DOI: 10.1016/j.cll.2018.02.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management.
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Affiliation(s)
- Amarpreet Bhalla
- Department of Pathology and Anatomical Sciences, Jacobs School of Buffalo, Buffalo, NY 14203, USA.
| | | | - Martin H Bluth
- Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA; Pathology Laboratories, Michigan Surgical Hospital, 21230 Dequindre Road, Warren, MI 48091, USA
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Zhou M, Wang X, Jiang L, Chen X, Bao X, Chen X. The diagnostic value of one step nucleic acid amplification (OSNA) in differentiating lymph node metastasis of tumors: A systematic review and meta-analysis. Int J Surg 2018; 56:49-56. [PMID: 29753955 DOI: 10.1016/j.ijsu.2018.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Accepted: 05/06/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study was clarify the diagnostic accuracy of one step nucleic acid amplification (OSNA) for differentiating metastatic lymph nodes from non-metastatic ones in patients with tumors (not including breast cancer). METHODS A systematic literature search for original diagnostic studies was performed in PubMed. Findings were pooled by using combined effect models and hierarchic summary receiver operating characteristic curve models. Meta-regression analysis and threshold effect evaluating were performed to explore the sources of heterogeneity affected classification accuracy. RESULTS 19 studies (803 positive and 4594 negative lymph nodes) were analyzed, including 4 different tumor types (head and neck cancers, gastrointestinal cancers, lung cancer and gynecological malignancies). In the studies of head and neck cancers the pooled sensitivity, specificity and area under the curve (AUC) of the OSNA method were 0.85(0.79-0.89), 0.96(0.92-0.98) and 0.91 (0.88-0.93), respectively. Similarly, the corresponding values in the studies of gastrointestinal cancers were 0.90(0.85-0.94), 0.96(0.94-0.98) and 0.97 (0.96-0.99), respectively. Because of limited number of studies, the other two tumor types were inestimable in the subsequent meta-analyses. CONCLUSIONS Pooled data suggest that the OSNA assay has a high diagnostic accuracy for the detection of lymph node metastases. For wide spread implementation, additional studies on other different types of tumors are warranted.
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Affiliation(s)
- Min Zhou
- Department of Thyroid and Breast Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu 214200, China.
| | - Xuzhen Wang
- Department of Thyroid and Breast Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu 214200, China.
| | - Liping Jiang
- Department of Gynecology and Obstetrics, Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214000, China.
| | - Xu Chen
- Department of Thyroid and Breast Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu 214200, China.
| | - Xin Bao
- Department of Thyroid and Breast Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu 214200, China.
| | - Xiang Chen
- Department of Thyroid and Breast Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu 214200, China.
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Fanfani F, Monterossi G, Ghizzoni V, Rossi ED, Dinoi G, Inzani F, Fagotti A, Gueli Alletti S, Scarpellini F, Nero C, Santoro A, Scambia G, Zannoni GF. One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer. PLoS One 2018; 13:e0195877. [PMID: 29698418 PMCID: PMC5919630 DOI: 10.1371/journal.pone.0195877] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 03/30/2018] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). MATERIAL AND METHODS From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. RESULTS Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. CONCLUSIONS The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.
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Affiliation(s)
- Francesco Fanfani
- Department of Medicine and Aging Sciences, University "G. D’Annunzio" of Chieti-Pescara, Chieti, Italy
| | - Giorgia Monterossi
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Viola Ghizzoni
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Esther D. Rossi
- Gynecologic Oncology Pathology Unit, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Giorgia Dinoi
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Frediano Inzani
- Gynecologic Oncology Pathology Unit, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Anna Fagotti
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Salvatore Gueli Alletti
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Francesca Scarpellini
- Gynecologic Oncology Pathology Unit, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Camilla Nero
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Angela Santoro
- Gynecologic Oncology Pathology Unit, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Giovanni Scambia
- Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Gian F. Zannoni
- Gynecologic Oncology Pathology Unit, Department of Women and Child Health, Catholic University of the Sacred Heart, Rome, Italy
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Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M. Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial. World J Surg 2018; 41:2378-2386. [PMID: 28508233 DOI: 10.1007/s00268-017-4051-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Rickenbacher
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Dimitri Aristotle Raptis
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Carsten T Viehl
- Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Ulrich Guller
- Division of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Jessica Rueff
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Zettl
- Viollier AG, Histopathology/Cytology, Basel, Switzerland
| | - Markus Zuber
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.
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Vodicka J, Mukensnabl P, Vejvodova S, Spidlen V, Kulda V, Topolcan O, Pesta M. A more sensitive detection of micrometastases of NSCLC in lymph nodes using the one-step nucleic acid amplification (OSNA) method. J Surg Oncol 2017; 117:163-170. [PMID: 29205350 DOI: 10.1002/jso.24826] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 08/10/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Detection of tumor cells in lymph nodes (LNs) removed during the treatment of pulmonary tumor by radical surgery is limited by the possibilities of standard histopathological methods. The goal of this study was to obtain more accurate pTNM status by a more sensitive detection of micrometastases in LNs. METHODS A total of 885 LNs, an average of 13.8 LNs per patient, were removed during 64 surgeries. LNs from the same zone were pooled together as a group, five groups of LNs were examined in each patient. A total of 320 groups of LNs were examined. One-step nucleic acid amplification (OSNA) method was compared to standard histopathological examination with haematoxylin-eosin (H&E) staining and CK19 immunohistochemistry, specifically by an ultimate analysis of all intraoperatively removed LNs. RESULTS Identical results for H&E and OSNA examinations were recorded in 286 groups of LNs (89.4%). In total, positive examinations were recorded in 27 groups of LNs (8.4%) using the OSNA method, which were H&E negative. In seven groups of LNs (2.2%), the H&E examination was positive, while OSNA method produced negative results. CONCLUSIONS The OSNA examination led to a higher pTNM stage classification in 14 (21.9%) patients. The clinical significance remains the subject of follow-up research.
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Affiliation(s)
- Josef Vodicka
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
| | - Petr Mukensnabl
- Sikl's Department of Pathology, University Hospital in Pilsen, Pilsen, Czech Republic
| | - Sarka Vejvodova
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
| | - Vladimir Spidlen
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
| | - Vlastimil Kulda
- Department of Medical Chemistry and Biochemistry, Charles University, Pilsen, Czech Republic
| | - Ondrej Topolcan
- Department of Nuclear Medicine-Immunoanalytic Laboratory, University Hospital in Pilsen, Pilsen, Czech Republic
| | - Martin Pesta
- Department of Biology, Charles University, Pilsen, Czech Republic.,Biomedical Centre, Charles University, Pilsen, Czech Republic
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Weixler B, Viehl CT, Warschkow R, Guller U, Ramser M, Sauter G, Zuber M. Comparative Analysis of Tumor Cell Dissemination to the Sentinel Lymph Nodes and to the Bone Marrow in Patients With Nonmetastasized Colon Cancer: A Prospective Multicenter Study. JAMA Surg 2017; 152:912-920. [PMID: 28593306 DOI: 10.1001/jamasurg.2017.1514] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Importance Small nodal tumor infiltrates (SNTI; isolated tumor cells and micrometastases) in sentinel lymph nodes and bone marrow micrometastases (BMM) were independently described as prognostic factors in patients with colon cancer. Objective To examine the association between the occurrence of SNTI and BMM as well as their prognostic relevance. Design, Setting, and Participants This prospective study was conducted at 3 university-affiliated institutions in Switzerland between May 2000 and December 2006. Statistical analyses were performed in October 2016. A total of 122 patients with stage I to III colon cancer were included. Follow-up time exceeded 6 years, with no patients lost to follow-up. Interventions Bone marrow aspiration from the iliac crests and in vivo sentinel lymph node mapping were performed during open standard oncological resection. Bone marrow aspirates were stained with the pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent multilevel sectioning and were stained with hematoxylin-eosin and the pancytokeratin marker AE1/AE3. Main Outcomes and Measures Association of SNTI in sentinel lymph nodes and BMM in patients with stage I to III colon cancer and the prognostic effect on disease-free survival (DFS) and overall survival (OS). Results Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of 71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found in a total of 21 patients (17.2%) and 46 patients (37.7%), respectively. The occurrence of BMM was not associated with the presence of SNTI by standard correlation (κ, -0.07; 95% CI, -0.29 to 0.14; P = .49) nor by univariate logistic regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67; P = .37) or multivariate logistic regression analysis (odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The presence of SNTI was an independent negative prognostic factor for DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93; P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45; P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06; P = .04; and HR, 2.68; 95% CI, 1.26-5.70; P = .01; respectively). The combined detection of BMM and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76; P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49; P = .03). Conclusions and Relevance This study demonstrates no association between the occurrence of SNTI and BMM in patients with stage I to III colon cancer. However, both SNTI and BMM are independent negative prognostic factors regarding DFS and OS, and the occurrence of both is associated with significantly worse prognosis compared with either one of them. Trial Registration clinicaltrials.gov Identifier: NCT00826579.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Carsten T Viehl
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Rene Warschkow
- Department of Surgery, Kantonsspital St Gallen, St Gallen, Switzerland.,Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Ulrich Guller
- Department of Oncology and Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Michaela Ramser
- Department of Surgery, University Hospital Basel, Basel, Switzerland
| | - Guido Sauter
- Department of Pathology, University Hospital Basel, Basel, Switzerland.,Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Markus Zuber
- Department Surgery, Cantonal Hospital Olten, Olten, Switzerland
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Kaczka KA, Pomorski L. One-step nucleic acid amplification analysis of sentinel lymph nodes in papillary thyroid cancer patients. Arch Med Sci 2017; 13:1416-1426. [PMID: 29181073 PMCID: PMC5701692 DOI: 10.5114/aoms.2017.65466] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 10/02/2016] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION It is essential to look for methods to define the need for central lymphadenectomy for papillary thyroid cancer patients. The aim is to determine the efficacy of one-step nucleic acid amplification (OSNA) and sentinel lymph node (SLN) biopsy in the intraoperative detection of nodal involvement. MATERIAL AND METHODS This prospective, experimental study enrolled 49 patients with clinically negative lymph nodes. Intraoperatively, 1% Patent Blue dye was injected intratumorally. Lymph nodes that stained blue were defined as SLNs. They were directly cut into blocks at 2-mm intervals. Nonadjacent blocks were subjected to either the OSNA assay or histological examination. RESULTS Sixty-five SLNs were found in 43 (87.8%) patients. There were 20 (30.8%) histopathologically positive SLNs. According to the OSNA, 22 (33.8%) SLNs were positive. The OSNA results were different from histopathology in 8 (12.3%) SLNs. The OSNA gave a positive result in 5 (7.7%) SLNs, while they were not involved according to the histopathology. However, OSNA upstaged N status from N0 to N1 only in 2 (3.1%) patients. Inverse results (histopathology +, OSNA-) were obtained in 3 (4.6%) SLNs. Positive and negative predictive values (PPV and NPV) for OSNA were 0.77 and 0.93, respectively. The concordance rate between examinations was 85.5%. CONCLUSIONS In some patients with clinically negative lymph nodes, OSNA and SLN biopsy may prevent unnecessary central lymphadenectomy. On the other hand, the sentinel lymph node biopsy may reveal the presence of potentially involved sentinel lymph nodes outside the central compartment. These SLNs can also be assessed by means of OSNA.
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Affiliation(s)
- Krzysztof A Kaczka
- Department of General and Oncological Surgery, Medical University of Lodz, Lodz, Poland
| | - Lech Pomorski
- Department of General and Oncological Surgery, Medical University of Lodz, Lodz, Poland
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Miyake Y, Mizushima T, Hata T, Takahashi H, Hanada H, Shoji H, Nomura M, Haraguchi N, Nishimura J, Matsuda C, Takemasa I, Doki Y, Maeda I, Mori M, Yamamoto H. Inspection of Perirectal Lymph Nodes by One-Step Nucleic Acid Amplification Predicts Lateral Lymph Node Metastasis in Advanced Rectal Cancer. Ann Surg Oncol 2017; 24:3850-3856. [PMID: 28924845 DOI: 10.1245/s10434-017-6069-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Lateral lymph node dissection (LLND) is performed for advanced rectal cancers in Japan; however, it can cause sexual and urinary dysfunction. The incidence of lateral LN metastasis is estimated at 7-13.9%; therefore, excessive rectal surgery with LLND should be avoided, especially for prophylactic purposes. To identify the patients who require LLND, we examined metastases in perirectal LNs by using a one-step nucleic acid amplification (OSNA) assay to predict lateral LN metastases. METHODS Twenty-five patients who underwent surgery with bilateral LN dissection due to T3-T4 rectal cancers were prospectively included in this study. Twenty-two patients (88.0%) received preoperative chemotherapy. Among 1052 LNs from 25 patients (median 40 per case), 135 perirectal LNs (median 6 per patient) were divided into three pieces and analyzed by OSNA, reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen mRNA, and pathological examination after surgery. These results were compared with the pathological diagnosis of lateral LNs. RESULTS Lateral LN metastases were present in 4 of 25 patients (16.0%). All of these patients were positive by OSNA for perirectal LN metastases. The OSNA assay had a sensitivity of 100%, specificity of 86%, positive predictive value of 57%, and negative predictive value (NPV) of 100% for predicting lateral LN metastases. CONCLUSIONS The findings from this prospective study suggest that the OSNA assay of perirectal LNs may be useful for determining when LLND is necessary because of its high NPV, even in patients treated with preoperative chemotherapy.
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Affiliation(s)
- Yuichiro Miyake
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Taishi Hata
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Hidekazu Takahashi
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Hiroyuki Hanada
- Laboratory for Clinical Investigation, Osaka University Hospital, Suita City, Osaka, Japan
| | - Hiroki Shoji
- Laboratory for Clinical Investigation, Osaka University Hospital, Suita City, Osaka, Japan
| | - Masatoshi Nomura
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Naotsugu Haraguchi
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Junichi Nishimura
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Chu Matsuda
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo City, Hokkaido, Japan
| | - Yuichiro Doki
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Ikuhiro Maeda
- Laboratory for Clinical Investigation, Osaka University Hospital, Suita City, Osaka, Japan
| | - Masaki Mori
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan
| | - Hirofumi Yamamoto
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan. .,Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
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Is it time for one-step nucleic acid amplification (OSNA) in colorectal cancer? A systematic review and meta-analysis. Tech Coloproctol 2017; 21:693-699. [PMID: 28887714 DOI: 10.1007/s10151-017-1690-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 08/01/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND Lymph node metastasis (LNM) is prognostic in colorectal cancer (CRC). However, evaluation by routine haematoxylin and eosin histology (HE) limits nodal examination and is subjective. Missed LNMs from tissue allocation bias (TAB) might under-stage disease, leading to under-treatment. One-step nucleic acid amplification (OSNA) for CK19 messenger ribonucleic acid (mRNA), a marker of LNM, analyses the whole node. The aim of the present systematic review and meta-analysis was to assess recent studies on OSNA versus HE and its implications for CRC staging and treatment. METHODS Databases including OVID, Medline and Google Scholar were searched for OSNA, LNM and CRC. Study results were pooled using a random-effects model. Summary receiver operator curves (SROC) assessed OSNA's performance in detecting LNM when compared to routine HE histology. RESULTS Five case-control studies analysing 4080 nodes from 622 patients were included. The summary estimates of pooled results for OSNA were sensitivity 0.90 [95% confidence interval (CI) 0.86-0.93], specificity 0.94 (95% CI 0.93-0.95) and diagnostic odds ratio 179.5 (CI 58.35-552.2, p < 0.0001). The SROC curve indicated a maximum joint sensitivity and specificity of 0.88 and area under the curve of 0.94, p < 0.0001. On average, 5.4% HE-negative nodes were upstaged by OSNA. CONCLUSIONS OSNA is as good as routine HE. It may avoid TAB and offer a more objective and standardised assay of LNM. However, for upstaging, its usefulness as an adjunct to HE or superiority to HE requires further assessment of the benefits, if any, of adjuvant therapy in patients upstaged by OSNA.
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Marhic A, Tremblay JF, Kaci R, André T, Eveno C, Pocard M. Molecular analysis of sentinel lymph node in colon carcinomas by one-step nucleic acid amplification (OSNA) reduces time to adjuvant chemotherapy interval. Dig Liver Dis 2017; 49:924-928. [PMID: 28668271 DOI: 10.1016/j.dld.2017.05.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 05/01/2017] [Accepted: 05/17/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC. METHODS We performed a prospective study analyzing 56 consecutive patients who had surgery for CC between July 2012 and October 2014, including 20 patients needing AC. SLN status was determined intraoperatively in 17 patients in the OSNA group; when positive, a portacath (PAC) was placed during the procedure for upcoming AC. In the remaining patients, we proceeded without SLN status determination and the PAC was installed after definitive histopathological analysis of the specimen if needed. RESULTS There was no difference between the groups regarding cancer staging, duration of hospitalization (7.5days in the OSNA group and 10days in the control group, p=0.43) and major complications (20% vs 30% respectively, p=0.55). The time interval between surgery and adjuvant chemotherapy was significantly shorter in the OSNA group at 35 (±8) days vs 67 (±36) days (p=0.021). CONCLUSION SLN status determination by the OSNA technique is safe, feasible and could significantly reduce time between surgery and adjuvant chemotherapy in a pilot study.
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Affiliation(s)
- Alix Marhic
- Digestive and Surgical Oncology Department, Lariboisière Hospital, Assistance publique-Hôpitaux de Paris, 2 rue Ambroise-Paré, 75010, Paris, France
| | - Jean-François Tremblay
- Digestive and Surgical Oncology Department, Lariboisière Hospital, Assistance publique-Hôpitaux de Paris, 2 rue Ambroise-Paré, 75010, Paris, France
| | - Rachid Kaci
- Department of Pathology, Lariboisière Hospital, Assistance publique-Hôpitaux de Paris, 2 rue Ambroise-Paré, 75010, Paris, France
| | - Thierry André
- Department of Medical Oncology, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; University Pierre et Marie Curie (UMPC), Paris VI,4 Place Jussieu, Paris 75005, France
| | - Clarisse Eveno
- Digestive and Surgical Oncology Department, Lariboisière Hospital, Assistance publique-Hôpitaux de Paris, 2 rue Ambroise-Paré, 75010, Paris, France; Paris Diderot University, USPC, Sorbonne Paris Cité, CART, INSERM U965, CART Carcinomatosis Angiogenesis and Translational Research F-74575 Paris, France
| | - Marc Pocard
- Digestive and Surgical Oncology Department, Lariboisière Hospital, Assistance publique-Hôpitaux de Paris, 2 rue Ambroise-Paré, 75010, Paris, France; Paris Diderot University, USPC, Sorbonne Paris Cité, CART, INSERM U965, CART Carcinomatosis Angiogenesis and Translational Research F-74575 Paris, France.
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Peg V, Sansano I, Vieites B, Bernet L, Cano R, Córdoba A, Sancho M, Martín MD, Vilardell F, Cazorla A, Espinosa-Bravo M, Pérez-García JM, Cortés J, Rubio IT, Ramón y Cajal S. Role of total tumour load of sentinel lymph node on survival in early breast cancer patients. Breast 2017; 33:8-13. [DOI: 10.1016/j.breast.2017.02.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 02/18/2017] [Accepted: 02/20/2017] [Indexed: 10/20/2022] Open
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Colling R, Yeung T, Hompes R, Kraus R, Cahill R, Mortensen N, Wang LM. OSNA testing for lymph node staging in colorectal cancer. J Clin Pathol 2017; 70:638-639. [DOI: 10.1136/jclinpath-2016-204299] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 02/13/2017] [Accepted: 03/10/2017] [Indexed: 01/11/2023]
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Rakislova N, Montironi C, Aldecoa I, Fernandez E, Bombi JA, Jimeno M, Balaguer F, Pellise M, Castells A, Cuatrecasas M. Lymph node pooling: a feasible and efficient method of lymph node molecular staging in colorectal carcinoma. J Transl Med 2017; 15:14. [PMID: 28088238 PMCID: PMC5237515 DOI: 10.1186/s12967-016-1114-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 12/22/2016] [Indexed: 01/11/2023] Open
Abstract
Background Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP). Results Molecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort). A median of 13 LNs (IQR 10–18) per patient were harvested in the individual cohort, and 18 LNs (IQR 13–25) per patient in the pooling cohort (p ≤ 0.001). The median of molecular assays performed in the pooling cohort was 2 per patient (IQR 1–3), saving a median of 16 assays/patient. The number of molecular assays performed in the individual cohort was 13 (IQR 10–18), corresponding to the number of LNs to be analyzed. The sensitivity and specificity of the pooling method for LN involvement (assessed by hematoxylin and eosin) were 88.9% (95% CI 56.5–98.0) and 79.2% (95% CI 68.9–86.8), respectively; concordance, 80.2%; PPV, 33.3%; NPV, 98.4%. The individual method had 100% sensitivity (95% CI 72.2–100), 44.6% specificity (95% CI 34.8–54.7), 50% concordance, 16.4% PPV, and 100% NPV. The amount of tumor burden detected in all LNs of a case, or total tumor load (TTL) was similar in both cohorts (p = 0.228). Conclusions LN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.
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Affiliation(s)
- Natalia Rakislova
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Carla Montironi
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Iban Aldecoa
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Eva Fernandez
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Josep Antoni Bombi
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Mireya Jimeno
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Maria Pellise
- Gastroenterology Department, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department-Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5, 08036, Barcelona, Spain. .,Tumor Bank, Biobanc Clinic-IDIBAPS and Xarxa de Bancs de Tumors de Catalunya (XBTC), Barcelona, Spain.
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Oka R, Nakashiro KI, Goda H, Iwamoto K, Tokuzen N, Hamakawa H. Annexin A8 is a novel molecular marker for detecting lymph node metastasis in oral squamous cell carcinoma. Oncotarget 2016; 7:4882-9. [PMID: 26700817 PMCID: PMC4826250 DOI: 10.18632/oncotarget.6639] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 12/05/2015] [Indexed: 01/17/2023] Open
Abstract
Cervical lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC), but its accurate assessment after sentinel node biopsy or neck dissection is often limited to the histopathological examination of only one or two sections. Previous our study showed the usefulness of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) targeting keratin 19 (KRT19) mRNA for the genetic detection of lymph node metastasis, but the sensitivity was insufficient. Here, we have attempted to identify novel molecular markers for OSCC cells in lymph nodes. We performed microarray analysis to identify genes overexpressed in 7 metastatic lymph nodes from OSCC patients, compared to 1 normal lymph node and 5 salivary glands from non-cancer patients. We then used real-time quantitative RT-PCR (qRT-PCR) and RT-LAMP to compare the expression of these genes in newly resected metastatic and normal lymph nodes. Of 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 mRNA were detected by qRT-PCR in metastatic lymph nodes but not in normal lymph nodes. Furthermore, ANXA8 mRNA expression was detected in all KRT19-negative metastatic lymph nodes. Both KRT19 and ANXA8 mRNA may be useful markers for detecting lymph node metastases in OSCC patients.
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Affiliation(s)
- Ryota Oka
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Koh-Ichi Nakashiro
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Hiroyuki Goda
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Kazuki Iwamoto
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Norihiko Tokuzen
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
| | - Hiroyuki Hamakawa
- Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
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One-step nucleic acid amplification (OSNA): where do we go with it? Int J Clin Oncol 2016; 22:3-10. [DOI: 10.1007/s10147-016-1030-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 08/08/2016] [Indexed: 12/29/2022]
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Aldecoa I, Atares B, Tarragona J, Bernet L, Sardon JD, Pereda T, Villar C, Mendez MC, Gonzalez-Obeso E, Elorriaga K, Alonso GL, Zamora J, Planell N, Palacios J, Castells A, Matias-Guiu X, Cuatrecasas M. Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study. Virchows Arch 2016; 469:385-94. [PMID: 27447172 PMCID: PMC5033997 DOI: 10.1007/s00428-016-1990-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 06/17/2016] [Accepted: 07/07/2016] [Indexed: 01/11/2023]
Abstract
Stage I–II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I–II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient’s total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/μL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62–0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I–II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.
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Affiliation(s)
- Iban Aldecoa
- Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5. Villarroel 170, Barcelona, 08036, Spain
| | - Begoña Atares
- Pathology Department, Alava University Hospital, Vitoria-Gasteiz, Spain
| | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain
| | - Laia Bernet
- Pathology Department, Hospital L. Alcanyis, Xativa, Spain
| | | | - Teresa Pereda
- Pathology Department, Hospital Costa del Sol, Marbella, Spain
| | - Carlos Villar
- Pathology Department, Hospital Reina Sofia, Cordoba, Spain
| | - M Carmen Mendez
- Pathology Department, Hospital Severo Ochoa, Leganes, Madrid, Spain
| | | | - Kepa Elorriaga
- Pathology Department, Hospital Onkologikoa, San Sebastian, Spain
| | | | - Javier Zamora
- Biostatistic Unit, Hospital Ramon y Cajal, Madrid, Spain
| | - Nuria Planell
- Gastroenterology Department and Bioinformatics Unit, CIBERehd, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Jose Palacios
- Pathology Department, Hospital Ramon y Cajal, Madrid, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | | | - Miriam Cuatrecasas
- Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5. Villarroel 170, Barcelona, 08036, Spain.
- CIBERehd, and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain.
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Aldecoa I, Montironi C, Planell N, Pellise M, Fernandez-Esparrach G, Gines A, Delgado S, Momblan D, Moreira L, Lopez-Ceron M, Rakislova N, Martinez-Palli G, Balust J, Bombi JA, de Lacy A, Castells A, Balaguer F, Cuatrecasas M. Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden. Surg Endosc 2016; 31:723-733. [PMID: 27324339 PMCID: PMC5266760 DOI: 10.1007/s00464-016-5026-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Accepted: 06/06/2016] [Indexed: 02/07/2023]
Abstract
Background Colorectal cancer (CRC) screening programs result in the detection of early-stage asymptomatic carcinomas suitable to be surgically cured. Lymph nodes (LN) from early CRC are usually small and may be difficult to collect. Still, at least 12 LNs should be analyzed from colectomies, to ensure a reliable pN0 stage. Presurgical endoscopic tattooing improves LN procurement. In addition, molecular detection of occult LN tumor burden in histologically pN0 CRC patients is associated with a decreased survival rate. We aimed to study the impact of presurgical endoscopic tattooing on the molecular detection of LN tumor burden in early colon neoplasms. Methods A prospective cohort study from a CRC screening-based population was performed at a tertiary academic hospital. LNs from colectomies with and without preoperative endoscopic tattooing were assessed by two methods, hematoxylin and eosin (HE), and RT-LAMP, to detect tumor cytokeratin 19 (CK19) mRNA. We compared the amount of tumor burden and LN yields from tattooed and non-tattooed specimens. Results HE and RT-LAMP analyses of 936 LNs were performed from 71 colectomies containing early carcinomas and endoscopically unresectable adenomas (8 pT0, 17 pTis, 27 pT1, 19 pT2); 47 out of 71 (66.2 %) were tattooed. Molecular positivity correlated with the presence of tattoo in LN [p < 0.001; OR 3.1 (95 % CI 1.7–5.5)]. A significantly higher number of LNs were obtained in tattooed specimens (median 17 LN vs. 14.5 LN; p = 0.019). Conclusions Endoscopic tattooing enables the analysis of those LNs most prone to harbor tumor cells and improves the number of LN harvested. Electronic supplementary material The online version of this article (doi:10.1007/s00464-016-5026-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Iban Aldecoa
- Pathology Department-Centre de Diagnostic Biomedic (CDB), Hospital Clínic, University of Barcelona (CIBERehd) and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Escala 3, Planta 5, Villarroel 170, 08036, Barcelona, Spain
| | - Carla Montironi
- Pathology Department-Centre de Diagnostic Biomedic (CDB), Hospital Clínic, University of Barcelona (CIBERehd) and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Escala 3, Planta 5, Villarroel 170, 08036, Barcelona, Spain
| | | | - Maria Pellise
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Gloria Fernandez-Esparrach
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Angels Gines
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | | | - Dulce Momblan
- Surgery Department, Hospital Clinic, Barcelona, Spain
| | - Leticia Moreira
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Maria Lopez-Ceron
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Natalia Rakislova
- Pathology Department-Centre de Diagnostic Biomedic (CDB), Hospital Clínic, University of Barcelona (CIBERehd) and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Escala 3, Planta 5, Villarroel 170, 08036, Barcelona, Spain
| | | | - Jaume Balust
- Anestesiology Department, ICMDiM, Hospital Clinic-IDIPAPS, Barcelona, Spain
| | - Josep Antoni Bombi
- Pathology Department-Centre de Diagnostic Biomedic (CDB), Hospital Clínic, University of Barcelona (CIBERehd) and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Escala 3, Planta 5, Villarroel 170, 08036, Barcelona, Spain
| | | | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Catalonia, Spain
| | - Miriam Cuatrecasas
- Pathology Department-Centre de Diagnostic Biomedic (CDB), Hospital Clínic, University of Barcelona (CIBERehd) and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Escala 3, Planta 5, Villarroel 170, 08036, Barcelona, Spain.
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Oezkan F, Khan AM, Hager T, Freitag L, Christoph D, Darwiche K. OSNA: A Fast Molecular Test Based on CK19 mRNA Concentration for Assessment of EBUS-TBNA Samples in Lung Cancer Patients. Clin Lung Cancer 2016; 17:198-204. [DOI: 10.1016/j.cllc.2015.09.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 09/03/2015] [Accepted: 09/11/2015] [Indexed: 01/06/2023]
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Weixler B, Warschkow R, Zettl A, Riehle HM, Guller U, Viehl CT, Zuber M. Intranodal Mapping Using Carbon Dye Results in More Accurate Lymph Node Staging in Colon Cancer Patients. World J Surg 2016; 39:2583-9. [PMID: 26154574 DOI: 10.1007/s00268-015-3130-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Small nodal tumor infiltrates (SNTI)-defined as isolated tumor cells and micrometastases-are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients. MATERIALS AND METHODS Isosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin-eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI. RESULTS Of a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9 %). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (p < 0.001). In 52 out of 59 LN (88.1 %), phagocytosed carbon dye was in close proximity to SNTI. CONCLUSIONS In the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping-which has been previously described for melanoma-can be extended to colon cancer patients.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
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Ong MLH, Schofield JB. Assessment of lymph node involvement in colorectal cancer. World J Gastrointest Surg 2016; 8:179-192. [PMID: 27022445 PMCID: PMC4807319 DOI: 10.4240/wjgs.v8.i3.179] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Revised: 10/24/2015] [Accepted: 01/04/2016] [Indexed: 02/06/2023] Open
Abstract
Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.
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Weixler B, Warschkow R, Güller U, Zettl A, von Holzen U, Schmied BM, Zuber M. Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. BMC Cancer 2016; 16:106. [PMID: 26879046 PMCID: PMC4754888 DOI: 10.1186/s12885-016-2130-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 02/04/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits ≤ 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.
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Affiliation(s)
- B. Weixler
- />Department of Surgery, Kantonsspital Olten, Baslerstrasse 150, CH - 4600 Olten, Switzerland
- />Department of Surgery, University Hospital Basel, Basel, Switzerland
| | - R. Warschkow
- />Department of Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland
- />Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - U. Güller
- />Department of Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
- />University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - A. Zettl
- />Viollier AG, Histopathology/Cytology, Basel, Switzerland
| | - U. von Holzen
- />Department of Surgery, University Hospital Basel, Basel, Switzerland
| | - B. M. Schmied
- />Department of Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - M. Zuber
- />Department of Surgery, Kantonsspital Olten, Baslerstrasse 150, CH - 4600 Olten, Switzerland
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Yamamoto H, Tomita N, Inomata M, Furuhata T, Miyake Y, Noura S, Kato T, Murata K, Hayashi S, Igarashi S, Itabashi M, Kameoka S, Matsuura N. OSNA-Assisted Molecular Staging in Colorectal Cancer: A Prospective Multicenter Trial in Japan. Ann Surg Oncol 2016; 23:391-396. [DOI: 10.1245/s10434-015-4880-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Masai K, Nakagawa K, Yoshida A, Sakurai H, Watanabe SI, Asamura H, Tsuta K. Cytokeratin 19 expression in primary thoracic tumors and lymph node metastases. Lung Cancer 2014; 86:318-23. [DOI: 10.1016/j.lungcan.2014.09.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2014] [Revised: 09/18/2014] [Accepted: 09/22/2014] [Indexed: 11/25/2022]
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Bhalla A, Zulfiqar M, Weindel M, Shidham VB. Molecular diagnostics in colorectal carcinoma. Clin Lab Med 2014; 33:835-59. [PMID: 24267189 DOI: 10.1016/j.cll.2013.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Molecular pathogenesis and classification of colorectal carcinoma are based on the adenoma-carcinoma sequence in the Vogelstein model, serrated polyp pathway, and microsatellite instability. The genetic basis for hereditary nonpolyposis colorectal cancer is based on detection of genetic mutations. Genetic testing for Lynch syndrome includes microsatellite instability, methylator phenotyping, BRAF mutation, and molecular testing. Molecular makers include quantitative multigene reverse transcriptase-polymerase chain reaction assay and KRAS and BRAF mutation analysis. Potential biomarkers include one-step nucleic acid amplification and epigenetic inactivation of endothelin 2 and endothelin 3 in colon cancer. Molecular screening approaches in colorectal cancer using stool DNA are under investigation.
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Affiliation(s)
- Amarpreet Bhalla
- Pathology Department, Harper University Hospital, Detroit Medical Center, Wayne State University School of Medicine, 3990 John R Street, Detroit, MI 48201, USA
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