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Angerilli V, Callegarin M, Govoni I, De Lisi G, Paudice M, Fugazzola P, Vanoli A, Parente P, Bergamo F, Luchini C, Dei Tos AP, Grillo F, Lonardi S, Mastracci L, Spolverato G, Fassan M. Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination. Gastric Cancer 2025:10.1007/s10120-025-01609-7. [PMID: 40205072 DOI: 10.1007/s10120-025-01609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/20/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Temporal and spatial molecular heterogeneity contributes to resistance to targeted and immune therapies in gastric and esophagogastric junction carcinoma (G/EGJ). This study evaluates differences in biomarker expression between primary G/EGJ and paired peritoneal metastases (PM). METHODS We analyzed 74 cases of primary G/EGJ and paired PM using immunohistochemistry for HER2, PD-L1, Claudin18 (CLDN18), DNA mismatch repair (MMR) proteins, p53, E-cadherin, and in situ hybridization for EBER. Biomarker concordance between primary and metastatic tumors was assessed. RESULTS Primary G/EGJ were predominantly poorly cohesive (45.9%) or mixed-type (37.8%). Regarding predictive biomarkers, low rates of HER2 overexpression (5.4%), MMR deficiency (4.1%), and EBER positivity (1.4%) were observed, while PD-L1 CPS ≥ 1 occurred in 79.7% of cases and CLDN18 positivity was observed in 31.1% of cases. Concordance was perfect for MMR and EBER, while PD-L1 showed the highest discordance (32.4%). HER2 had a low discordance rate (2.7%). CLDN18 exhibited good concordance (86.5%) and showed consistent positivity in PD-L1- and HER2-negative primary tumors (28.6%). CONCLUSION G/EGJ with PM show distinct molecular features and spatial heterogeneity, with MMR, EBER, and HER2 demonstrating strong concordance, while PD-L1 showed greater variability. As for novel biomarkers, CLDN18.2 shows substantial concordance between primary G/EGJ and PM and could be a promising target in HER2/PD-L1-negative G/EGJ with PM.
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Affiliation(s)
- Valentina Angerilli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
- ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Matilde Callegarin
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
| | - Ilaria Govoni
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Giuseppe De Lisi
- IRCCS San Matteo Hospital, Pavia, Italy
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Michele Paudice
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Paola Fugazzola
- General Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandro Vanoli
- IRCCS San Matteo Hospital, Pavia, Italy
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | | | - Claudio Luchini
- Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy
| | - Angelo Paolo Dei Tos
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
| | - Federica Grillo
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Sara Lonardi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Luca Mastracci
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy.
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
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Shi H, Yang H, Yan S, Zhang Q, Wang X. Development and validation of nomograms based on the SEER database for the risk factors and prognosis of distant metastasis in gastric signet ring cell carcinoma. Medicine (Baltimore) 2024; 103:e40382. [PMID: 39496020 PMCID: PMC11537633 DOI: 10.1097/md.0000000000040382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 10/16/2024] [Indexed: 11/06/2024] Open
Abstract
Poor prognosis in patients with distant metastasis of gastric signet ring cell carcinoma (GSRC), and there are few studies on the development and validation of the diagnosis and prognosis of distant metastasis of GSRC. The Surveillance, Epidemiology, and End Results database was used to identify patients with GSRC from 2004 to 2019. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for distant metastasis of GSRC, while univariate and multivariate Cox proportional hazard regression analysis were used to determine independent prognostic factors for patients with distant metastasis of GSRC. Two nomograms were established, and model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. A total of 9703 cases with GSRC were enrolled, among which 2307 cases (23.78%) were diagnosed with distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis included age, race, and T stage. Independent prognostic factors included T stage, chemotherapy, and surgery. The receiver operating characteristic curve, calibration curve, decision curve analysis curve, and Kaplan-Meier survival curve of the training set and validation set confirmed that the 2 nomograms could accurately predict the occurrence and prognosis of distant metastasis in GSRC. Two nomograms can serve as effective prediction tools for predicting distant metastasis in GSRC patients and the prognosis of patients with distant metastasis. They have a certain clinical reference value.
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Affiliation(s)
- Haomin Shi
- Department of Public Health, Qinghai University School of Medicine, Xining, China
- Qinghai Provincial People’s Hospital, Xining, China
| | - Huilian Yang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
| | - Su Yan
- Affiliated Hospital of Qinghai University, Xining, China
| | - Qi Zhang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
| | - Xingbin Wang
- Department of Public Health, Qinghai University School of Medicine, Xining, China
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Grinlinton M, Furkert C, Maurice A, Angelo N, Booth M. Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review. World J Gastrointest Surg 2024; 16:1629-1636. [PMID: 38983359 PMCID: PMC11230026 DOI: 10.4240/wjgs.v16.i6.1629] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/23/2024] [Accepted: 04/28/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Upper gastrointestinal (GI) signet ring cell carcinomas (SRCC) confer a poor prognosis. The benefit of operative intervention for this patient group is controversial in terms of overall survival. AIM To investigate factors relating to survival in patients with upper GI SRCC. METHODS A retrospective, tertiary, single-centre review of patients who were diagnosed with oesophageal, gastroesophageal junction and gastric SRCC was performed. The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management. Secondary outcomes included assessing the relationship between demographic and histopathological factors, and survival. RESULTS One hundred and thirty-one patients were included. The one-year survival for the operative group was 81% and for the nonoperative group was 19.1%. The five-year survival in the operative group was 28.6% vs 1.5% in the nonoperative group. The difference in overall survival between groups was statistically significant (HR 0.19, 95%CI (0.13-0.30), P < 0.001). There was no difference in survival when adjusting for age, smoking status or gender. On multivariate analysis, patients who underwent surgical management, those with a lower stage of disease, and those with a lower Charlson Comorbidity Index (CCI) had significantly improved survival. CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery. Offering surgery to a carefully selected patient group may improve the outcome for this disease.
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Affiliation(s)
- Megan Grinlinton
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Chris Furkert
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Andrew Maurice
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
| | - Neville Angelo
- Department of Pathology, North Shore Hospital, Auckland 0620, New Zealand
| | - Michael Booth
- Department of General Surgery, North Shore Hospital, Auckland 0620, New Zealand
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4
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Valkema MJ, Vos A, van der Post RS, Ooms AHAG, Oudijk L, Eyck BM, Lagarde SM, Wijnhoven BPL, Klarenbeek BR, Rosman C, van Lanschot JJB, Doukas M. The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells. THE JOURNAL OF PATHOLOGY: CLINICAL RESEARCH 2023. [DOI: 10.1002/cjp2.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/24/2023] [Accepted: 03/11/2023] [Indexed: 03/29/2023]
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Guo Y, Wang Q, Tian Q, Bo C, Li N, Zhang S, Li P. Clinicopathological Features and Prognostic-Related Risk Factors of Gastric Signet Ring Cell Carcinoma: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3473445. [PMID: 36035278 PMCID: PMC9410921 DOI: 10.1155/2022/3473445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/06/2022] [Accepted: 07/17/2022] [Indexed: 11/23/2022]
Abstract
Background Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.
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Affiliation(s)
- Ying Guo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qian Wang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Qing Tian
- Thoracic Surgery Department, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Changwen Bo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Na Li
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Sujing Zhang
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Peishun Li
- Department of Oncology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, China
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6
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Zaafouri H, Jouini R, Khedhiri N, Khanchel F, Cherif M, Mesbahi M, Daghmouri A, Mahmoudi W, Akremi S, Sabbah M, Benzarti Y, Hadded D, Gargouri D, Bader MB, Maamer AB. Comparison between signet-ring cell carcinoma and non-signet-ring cell carcinoma of the stomach: clinicopathological parameters, epidemiological data, outcome, and prognosis-a cohort study of 123 patients from a non-endemic country. World J Surg Oncol 2022; 20:238. [PMID: 35858903 PMCID: PMC9297662 DOI: 10.1186/s12957-022-02699-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 06/29/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity. METHODS This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients. RESULTS The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635). CONCLUSION Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.
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Affiliation(s)
- Haithem Zaafouri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia.
| | - Raja Jouini
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Nizar Khedhiri
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Fatma Khanchel
- Department of Cytopathology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mona Cherif
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Meryam Mesbahi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Aziz Daghmouri
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Wiem Mahmoudi
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Soumaya Akremi
- Department of Anesthesiology, Habib Thameur Hospital, Tunis, Tunisia
| | - Meriam Sabbah
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Yazid Benzarti
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dhafer Hadded
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Dalila Gargouri
- Department of Gastroenterology, Habib Thameur Hospital, Tunis, Tunisia
| | - Mourad Ben Bader
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
| | - Anis Ben Maamer
- Department of General Surgery, Habib Thameur Hospital, Tunis, Tunisia
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Wang YF, Xu SY, Wang Y, Che GW, Ma HT. Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma: A systematic review and meta-analysis. World J Clin Cases 2021; 9:10969-10978. [PMID: 35047607 PMCID: PMC8678857 DOI: 10.12998/wjcc.v9.i35.10969] [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: 06/18/2021] [Revised: 07/29/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The clinical significance of signet ring cells (SRCs) in surgical esophageal and esophagogastric junction adenocarcinoma (EEGJA) remains unclear now.
AIM To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies.
METHODS The PubMed, Web of Science, and EMBASE electronic databases were searched for the relevant literature up to March 28, 2021. The relative risk (RR) with 95% confidence interval (CI) was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients, and the hazard ratio (HR) with 95%CI was calculated to explore the impact of SRC on the prognosis. All statistical analyses were conducted with STATA 12.0 software.
RESULTS A total of ten articles were included, involving 30322 EEGJA patients. The pooled results indicated that the presence of SRCs was significantly associated with tumor location (RR: 0.76, 95%CI: 0.61-0.96, P = 0.022; I2 = 49.4%, P = 0.160) and tumor-node-metastasis stage (RR: 1.30, 95%CI: 1.02-1.65, P = 0.031; I2 = 73.1%, P = 0.002). Meanwhile, the presence of SRCs in surgical EEGJA patients predicted a poor overall survival (HR: 1.36, 95%CI: 1.12-1.65, P = 0.002; I2 = 85.7%, P < 0.001) and disease-specific survival (HR: 1.86, 95%CI: 1.55-2.25, P < 0.001; I2 = 63.1%, P = 0.043).
CONCLUSION The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients. However, more high-quality studies are still needed to verify the above findings.
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Affiliation(s)
- Yi-Fan Wang
- Department of Thoracic Surgery, Affiliated Hospital of Chengdu University, Chengdu 610081, Sichuan Province, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Si-Yu Xu
- West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Wang
- Department of Thoracic Surgery, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Guo-Wei Che
- Department of Thoracic Surgery, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Hai-Tao Ma
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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8
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Bonnot PE, Lintis A, Mercier F, Benzerdjeb N, Passot G, Pocard M, Meunier B, Bereder JM, Abboud K, Marchal F, Quenet F, Goere D, Msika S, Arvieux C, Pirro N, Wernert R, Rat P, Gagnière J, Lefevre JH, Courvoisier T, Kianmanesh R, Vaudoyer D, Rivoire M, Meeus P, Villeneuve L, Piessen G, Glehen O. Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study). Br J Surg 2021; 108:1225-1235. [PMID: 34498666 DOI: 10.1093/bjs/znab200] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/07/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.
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Affiliation(s)
- P E Bonnot
- Department of Surgical Oncology, Centre Georges Francois Leclerc, Dijon, France.,Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - A Lintis
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of General Surgery, CHU Lille, Lille, France
| | - F Mercier
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of Surgical Oncology, Centre Hospitalier Universitaire de Montreal, Montreal, Quebec, Canada
| | - N Benzerdjeb
- Pathology Department, CHU Lyon Sud, Hospices Civils de Lyon, University of Lyon, Lyon, France
| | - G Passot
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Pocard
- Department of Surgical Oncology, Hôpital Lariboisière, Paris, France
| | - B Meunier
- Department of Surgical Oncology, CHU Pontchaillou, Rennes, France
| | - J M Bereder
- Department of Surgical Oncology, CHU L'Archet, Nice, France
| | - K Abboud
- Department of Surgical Oncology, CHU St Etienne, St Etienne, France
| | - F Marchal
- Department of Surgical Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France
| | - F Quenet
- Department of Surgical Oncology, Centre Val D'Aurelle, Montpellier, France
| | - D Goere
- Department of Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - S Msika
- Department of Surgical Oncology, CHU Louis Mourier, Paris, France
| | - C Arvieux
- Department of Surgical Oncology, CHU La Tronche, Grenoble, France
| | - N Pirro
- Department of Surgical Oncology, CHU La Timone, Marseille, France
| | - R Wernert
- Department of Surgical Oncology, Institut Paul Papin, Angers, France
| | - P Rat
- Department of Surgical Oncology, CHU Le Bocage, Dijon, France
| | - J Gagnière
- Department of Surgical Oncology, CHU Clermont-Ferrand, Clermont Ferrand, France
| | - J H Lefevre
- Department of Surgical Oncology, Hôpital Saint-Antoine, AP-HP, Paris, Sorbonne Université, Paris, France
| | - T Courvoisier
- Department of Surgical Oncology, CHU Poitiers, Poitiers, France
| | - R Kianmanesh
- Department of Surgical Oncology, CHU Reims, Reims, France
| | - D Vaudoyer
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - P Meeus
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - L Villeneuve
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Unité de Recherche Clinique, Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France
| | - G Piessen
- Department of General Surgery, CHU Lille, Lille, France
| | - O Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
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Fiocca R, Mastracci L, Lugaresi M, Grillo F, D’Errico A, Malvi D, Spaggiari P, Tomezzoli A, Albarello L, Ristimäki A, Bottiglieri L, Bonora E, Krishnadath KK, Raulli GD, Rosati R, Fumagalli Romario U, De Manzoni G, Räsänen J, Mattioli S. The Prognostic Impact of Histology in Esophageal and Esophago-Gastric Junction Adenocarcinoma. Cancers (Basel) 2021; 13:5211. [PMID: 34680360 PMCID: PMC8533974 DOI: 10.3390/cancers13205211] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/11/2021] [Accepted: 10/13/2021] [Indexed: 12/18/2022] Open
Abstract
Stage significantly affects survival of esophageal and esophago-gastric junction adenocarcinomas (EA/EGJAs), however, limited evidence for the prognostic role of histologic subtypes is available. The aim of the study was to describe a morphologic approach to EA/EGJAs and assess its discriminating prognostic power. Histologic slides from 299 neoadjuvant treatment-naïve EA/EGJAs, resected in five European Centers, were retrospectively reviewed. Morphologic features were re-assessed and correlated with survival. In glandular adenocarcinomas (240/299 cases-80%), WHO grade and tumors with a poorly differentiated component ≥6% were the most discriminant factors for survival (both p < 0.0001), distinguishing glandular well-differentiated from poorly differentiated adenocarcinomas. Two prognostically different histologic groups were identified: the lower risk group, comprising glandular well-differentiated (34.4%) and rare variants, such as mucinous muconodular carcinoma (2.7%) and diffuse desmoplastic carcinoma (1.7%), versus the higher risk group, comprising the glandular poorly differentiated subtype (45.8%), including invasive mucinous carcinoma (5.7%), diffuse anaplastic carcinoma (3%), mixed carcinoma (6.7%) (CSS p < 0.0001, DFS p = 0.001). Stage (p < 0.0001), histologic groups (p = 0.001), age >72 years (p = 0.008), and vascular invasion (p = 0.015) were prognostically significant in the multivariate analysis. The combined evaluation of stage/histologic group identified 5-year cancer-specific survival ranging from 87.6% (stage II, lower risk) to 14% (stage IVA, higher risk). Detailed characterization of histologic subtypes contributes to EA/EGJA prognostic prediction.
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Affiliation(s)
- Roberto Fiocca
- Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16125 Genova, Italy; (L.M.); (F.G.)
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
| | - Luca Mastracci
- Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16125 Genova, Italy; (L.M.); (F.G.)
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
| | - Marialuisa Lugaresi
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (M.L.); (E.B.); (S.M.)
- Division of Thoracic Surgery, Maria Cecilia Hospital, GVM Care & Research Group, Cotignola, 48022 Ravenna, Italy
| | - Federica Grillo
- Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16125 Genova, Italy; (L.M.); (F.G.)
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
| | - Antonietta D’Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (A.D.); (D.M.)
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
| | - Deborah Malvi
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (A.D.); (D.M.)
| | - Paola Spaggiari
- Unit of Anatomic Pathology, Humanitas University, 20089 Milan, Italy;
| | - Anna Tomezzoli
- Unit of Anatomic Pathology, Azienda Ospedaliera di Verona, 37122 Verona, Italy;
| | - Luca Albarello
- Pathology Unit, San Raffaele Scientific Institute, 20135 Milan, Italy;
| | - Ari Ristimäki
- Department of Pathology, HUSLAB and HUS Diagnostic Center, University of Helsinki, 00170 Helsinki, Finland;
- Helsinki University Hospital, 00170 Helsinki, Finland
| | - Luca Bottiglieri
- Unit of Anatomic Pathology, Istituto Europeo di Oncologia, 20122 Milan, Italy;
| | - Elena Bonora
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (M.L.); (E.B.); (S.M.)
- Unit of Medical Genetics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy
| | - Kausilia K. Krishnadath
- Laboratory of Experimental Medicine and Pediatrics (LEMP), Department of Gastroenterology and Hepatology, University Hospital Antwerp, 2650 Antwerp, Belgium;
| | | | - Riccardo Rosati
- Department of Gastrointestinal Surgery, San Raffaele Hospital, Vita-Salute San Raffaele University, 20135 Milan, Italy;
| | | | - Giovanni De Manzoni
- Department of Surgery, General and Upper G.I. Surgery Division, University of Verona, 37126 Verona, Italy;
| | - Jari Räsänen
- Department of General Thoracic and Esophageal Surgery, Helsinki University Hospital, 00170 Helsinki, Finland;
| | - Sandro Mattioli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (M.L.); (E.B.); (S.M.)
- Division of Thoracic Surgery, Maria Cecilia Hospital, GVM Care & Research Group, Cotignola, 48022 Ravenna, Italy
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10
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Wang S, Li J, You J, Zhou Y. Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the gallbladder. BMC Gastroenterol 2021; 21:248. [PMID: 34090347 PMCID: PMC8180115 DOI: 10.1186/s12876-021-01831-4] [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] [Received: 01/25/2021] [Accepted: 05/24/2021] [Indexed: 02/08/2023] Open
Abstract
Background Signet ring cell carcinoma (SRC) is a rare histological subtype of gallbladder adenocarcinoma. The current study evaluates the clinicopathologic features and prognosis of SRC. Methods Patients with adenocarcinoma of the gallbladder were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2016. Overall survival (OS) and cancer-specific survival (CSS) of patients who had SRC were compared with those of patients who had non-SRC using Cox regression and propensity score methods. Results Of 22,781 gallbladder adenocarcinomas retrieved, 377 (1.7%) were SRC and the other 22,404 were non-SRC. SRC was more significantly associated with older age, female gender, poor differentiation, advanced tumor stage, lymph node metastasis, distant metastasis, and advanced AJCC stage. The 5-year OS and CSS in the SRC group were 7.2 and 6.5%, respectively, both of which were significantly worse than the 13.2 and 13.3% seen in the SRC group (P = 0.002 and P = 0.012, respectively). This survival disadvantage persisted in multivariable analyses [hazard ratio (HR) = 1.256, P = 0.021 and HR = 1.211, P = 0.036] and after propensity score matching (OS: HR = 1.341, P = 0.012 and CSS: HR = 1.625, P = 0.005). Surgery in combination with chemotherapy improved OS of gallbladder SRC patients compared with surgery alone (HR = 0.726, P = 0.036) or chemotherapy alone (HR = 0.433, P < 0.001). Conclusion Patients with SRC of the gallbladder have distinct clinicopathological features with poor prognosis. Surgery in combination with chemotherapy can improve survival.
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Affiliation(s)
- Shijie Wang
- Department of Hepatobiliary and Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Jiayi Li
- Department of Hepatobiliary and Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Jun You
- Department of Hepatobiliary and Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Yanming Zhou
- Department of Hepatobiliary and Pancreatovascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.
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11
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Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers. Biochim Biophys Acta Rev Cancer 2021; 1876:188538. [PMID: 33862149 DOI: 10.1016/j.bbcan.2021.188538] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 12/12/2022]
Abstract
Twenty mucin genes have been identified and classified in two groups (encoding secreted and membrane-bound proteins). Secreted mucins participate in mucus formation by assembling a 3-dimensional network via oligomerization, whereas membrane-bound mucins are anchored to the outer membrane mediating extracellular interactions and cell signaling. Both groups have been associated with carcinogenesis progression in epithelial cancers, and are therefore considered as potential therapeutic targets. In the present review, we discuss the link between mucin expression patterns and patient survival and propose mucins as prognosis biomarkers of epithelial cancers (esophagus, gastric, pancreatic, colorectal, lung, breast or ovarian cancers). We also investigate the relationship between mucin expression and overall survival in the TCGA dataset. In particular, epigenetic mechanisms regulating mucin gene expression, such as aberrant DNA methylation and histone modification, are interesting as they are also associated with diagnosis or prognosis significance. Indeed, mucin hypomethylation has been shown to be associated with carcinogenesis progression and was linked to prognosis in colon cancer or pancreatic cancer patients. Finally we describe the relationship between mucin expression and non-coding RNAs that also may serve as biomarkers. Altogether the concomitant knowledge of specific mucin-pattern expression and epigenetic regulation could be translated as biomarkers with a better specificity/sensitivity performance in several epithelial cancers.
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12
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Solomon D, Abbas M, Feferman Y, Haddad R, Perl G, Kundel Y, Morgenstern S, Menasherov N, Kashtan H. Signet Ring Cell Features are Associated with Poor Response to Neoadjuvant Treatment and Dismal Survival in Patients with High-Grade Esophageal Adenocarcinoma. Ann Surg Oncol 2021; 28:4929-4940. [PMID: 33709175 DOI: 10.1245/s10434-021-09644-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND While the prognosis of patients with locoregional esophageal adenocarcinoma (EAC) has improved in the neoadjuvant treatment (NAT) era, high-grade histology (G3) is still associated with a limited treatment response. We sought to investigate oncologic outcomes in patients after esophagectomy for G3 EAC and to identify predictors of poor survival among these patients. METHODS Patients with EAC who underwent resection with curative intent in 2011-2018 were divided by histologic grade (G3, G1/2) and compared for overall survival (OS). Cox regression was performed to analyze the response to NAT and the predictive role of signet ring cell (SRC) features. RESULTS The cohort included 163 patients, 94 (57.7%) with G3 histology. NAT was administered to 69 (73.4%) patients. Following resection, OS in the G3 EAC group was 30 months (95% confidence interval [CI] 23.9-36.1). On univariate analysis, G3 disease (p = 0.050) and SRC features (p = 0.019) predicted low OS. Median survival in the G3 EAC group was worse in patients with SRC histology (18 months, 95% CI 8.6-27.4) than those without (30 months, 95% CI 23.8-36.1; p = 0.041). No patients with SRC histology were alive at 5 years of follow-up. Among all patients administered NAT, 88.2% of those with SRC showed minimal or no pathologic response and only 27.8% were downstaged. CONCLUSIONS High-grade histology was found in most patients with EAC and predicted poor survival and treatment response. SRC features in patients with G3 disease were associated with lower OS. The benefit of NAT for G3 EAC in patients with SRC histology appears limited.
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Affiliation(s)
- Daniel Solomon
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Muhammad Abbas
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Feferman
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Riad Haddad
- Department of Surgery, Carmel Carmel Medical Center, Affiliated with the Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Gali Perl
- Davidoff Cancer Center, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yulia Kundel
- Davidoff Cancer Center, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sara Morgenstern
- Department of Pathology, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nikolai Menasherov
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hanoch Kashtan
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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13
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Khan N, Donohoe CL, Phillips AW, Griffin SM, Reynolds JV. Signet ring gastric and esophageal adenocarcinomas: characteristics and prognostic implications. Dis Esophagus 2020; 33:5831347. [PMID: 32378712 DOI: 10.1093/dote/doaa016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/11/2020] [Indexed: 12/11/2022]
Abstract
Controversy exists as to the relevance of the signet ring carcinoma (SRC) histological subtype of esophagogastric adenocarcinoma to long-term prognosis, with some studies reporting a worsened oncological outcome and others no clinically relevant impact. A retrospective analysis of outcomes of patients who underwent surgery with curative intent in two high-volume centers (2000-2015) was undertaken. Tumors were analyzed according to location (esophageal, junctional or gastric). Propensity score matching (PSM) analysis was used to match patients with signet ring histology to those without (195 SRC vs. 573 non-SRC), based on age, tumor location, use of neoadjuvant and adjuvant chemotherapy and pathological stage. A total of 2,500 patients with esophagogastric adenocarcinomas were treated, of whom 198 (7.9%) had signet ring histology. Signet ring tumors were more likely to have positive lymph nodes at pathological analysis (59% vs. 50%, P = 0.009). The 5-year survival rate for patients with early signet ring tumors (Stage 0/I/IIa) was 65% versus 85% for other early cancers (P < 0.003). Patients with esophageal signet ring tumors had a particularly poor prognosis with 23% 2-year survival and none alive at 5 years. With PSM, overall survival (OS) was significantly poorer in the signet ring group (44.3 ± 8.6 vs. 59.8 ± 8.5 months, 5-year OS 41% vs. 50%, P = 0.027). Signet ring cells within esophagogastric adenocarcinoma are associated with a poorer prognosis. Genomic studies to identify the composition of such tumors as well as identify strategies to improve treatment for this subtype are warranted.
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Affiliation(s)
- Niall Khan
- National Esophageal and Gastric Cancer Centre, St. James's Hospital, Dublin, Ireland.,Trinity College Dublin, Dublin, Ireland
| | - Claire L Donohoe
- National Esophageal and Gastric Cancer Centre, St. James's Hospital, Dublin, Ireland.,Trinity College Dublin, Dublin, Ireland.,Northern Oesophago-gastric Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - Alexander W Phillips
- Northern Oesophago-gastric Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - S Michael Griffin
- Northern Oesophago-gastric Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - John V Reynolds
- National Esophageal and Gastric Cancer Centre, St. James's Hospital, Dublin, Ireland.,Trinity College Dublin, Dublin, Ireland
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14
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Palmieri LJ, Dermine S, Abou Ali E, Lavolé J, Belle A, Beuvon F, Terris B, Chaussade S, Coriat R, Barret M. Early esophageal signet ring cell carcinoma: A contraindication to endoscopic resection? Clin Res Hepatol Gastroenterol 2020; 44:e98-e102. [PMID: 32033926 DOI: 10.1016/j.clinre.2020.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/30/2019] [Accepted: 01/06/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Endoscopic resection is a standard-of-care for early esophageal neoplasia. Early gastric signet ring cell carcinoma (SRCC) can be safely managed by endoscopic resection, if the early SRCC is limited to the mucosa and less than 15mm, with a low lymph node metastasis rate. It is not known if esophageal signet ring cell carcinoma is amenable to endoscopic resection. METHODS We retrospectively collected demographic, procedural, oncologic and follow-up data from all patients with esophageal SRCC resected endoscopically at our institution, and compared them to those of patients with endoscopically resected poorly differentiated esophageal adenocarcinomas. RESULTS Between 2016 and 2018, 170 endoscopic resections were performed for esophageal neoplasms, among which 7 patients with SRCC and 6 patients with poorly differentiated early adenocarcinomas were identified. The histologically complete (R0) resection rate was 28.6% (2/7) for SRCC vs. 100% for poorly differentiated adenocarcinomas (P=0.04). The presence of lymphovascular invasion or deep submucosal invasion led to curative resection rates of 14.2% (1/7) and 66.6% (4/6) for SRCC and poorly differentiated adenocarcinomas, respectively (P=0.1). CONCLUSION Endoscopic resection of early esophageal SRCC is neither histologically complete, nor curative in the majority of cases. These data argue against upfront endoscopic resection when SRCC is evidenced on esophageal biopsies.
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Affiliation(s)
- Lola-Jade Palmieri
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France.
| | - Solène Dermine
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France
| | - Julie Lavolé
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France
| | - Arthur Belle
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France
| | | | - Benoît Terris
- University of Paris, Paris, France; Pathology Department, Cochin Hospital, 75014 Paris, France
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France
| | - Maximilien Barret
- Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France
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15
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Corsini EM, Foo WC, Mitchell KG, Zhou N, Maru DM, Ajani JA, Hofstetter WL, Correa AM, Antonoff MB, Lin SH, Mehran RJ, Rajaram R, Rice DC, Roth JA, Sepesi B, Swisher SG, Vaporciyan AA, Walsh GL. Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy. J Thorac Cardiovasc Surg 2020; 162:1404-1412.e2. [PMID: 33010880 DOI: 10.1016/j.jtcvs.2020.08.108] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.
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Affiliation(s)
- Erin M Corsini
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Wai Chin Foo
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Kyle G Mitchell
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Nicolas Zhou
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Dipen M Maru
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex.
| | - Arlene M Correa
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Mara B Antonoff
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Steven H Lin
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Reza J Mehran
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Ravi Rajaram
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - David C Rice
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Jack A Roth
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Stephen G Swisher
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Ara A Vaporciyan
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Garrett L Walsh
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex
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16
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Li Y, Zhu Z, Ma F, Xue L, Tian Y. Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges. Cancer Manag Res 2020; 12:7973-7981. [PMID: 32943931 PMCID: PMC7478370 DOI: 10.2147/cmar.s268032] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/15/2020] [Indexed: 12/26/2022] Open
Abstract
Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.
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Affiliation(s)
- Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhikai Zhu
- School of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Fuhai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
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17
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Tang A, Rappaport J, Raja S, Bribriesco AC, Sudarshan M, Siddiqui HU, Raymond D, Murthy SC, Ahmad U. Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma. Ann Thorac Surg 2020; 111:214-222. [PMID: 32579884 DOI: 10.1016/j.athoracsur.2020.04.134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 03/21/2020] [Accepted: 04/27/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Signet ring cell (SRC) histology is regarded as a poor prognostic indicator for esophageal cancer. The objectives of this study were to understand the clinical presentation and stage-specific survival outcomes of patients with SRC and nonsignet adenocarcinoma (AC). METHODS From 2004 to 2016, 140,324 patients were diagnosed with esophageal and gastroesophageal junction cancers in the National Cancer Database. Demographics, tumor variables, and treatment were studied. Overall survival was shown by the Kaplan-Meier method, and random survival forest identified important predictors. RESULTS SRC patients (N = 3825) comprised roughly 3% of esophageal cancers per year. SRC patients were less likely to present at early stage disease (cStage I: 10.2% vs 17.8% for AC; P < .001) and more likely to have pathologic upstaging (28% vs 16%, P < .001) and less pathologic downstaging after neoadjuvant therapy (36% vs 48%, P < .001). More SRC patients had positive margins after resection (15% vs 6.0%, P < .001). In a stage-matched comparison median survival for SRC patients was worse than for AC patients (cStage I: 60 vs 113 months; cStage II: 31 vs 40 months; cStage III: 22 vs 30 months). Clinical tumor and nodal stage, chemotherapy sequence, and age were important predictors of survival. CONCLUSIONS SRC patients had worse survival than their AC counterparts. Worse biology and higher rates of incomplete resection in SRC should steer patients away from undergoing limited resection, such as endoscopic submucosal dissection, even when identified at very early stages. In future esophageal cancer staging iterations, separating SRC from AC appears to be indicated because of their different clinical behavior and response to therapy.
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Affiliation(s)
- Andrew Tang
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Jesse Rappaport
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Siva Raja
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Alejandro C Bribriesco
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Monisha Sudarshan
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Hafiz U Siddiqui
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Daniel Raymond
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Sudish C Murthy
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio
| | - Usman Ahmad
- Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio.
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18
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Diniz TP, da Costa WL, Fonseca de Jesus VH, Ribeiro HSC, Diniz AL, de Godoy AL, de Farias IC, Torres SM, Felismino TC, Coimbra FJF. Does hipec improve outcomes in gastric cancer patients treated with perioperative chemotherapy and radical surgery? A propensity-score matched analysis. J Surg Oncol 2020; 121:823-832. [PMID: 31950511 DOI: 10.1002/jso.25823] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 12/22/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with improved survival when compared with surgery alone for non-metastatic gastric cancer patients in randomized trials and meta-analyses. However, little evidence is available regarding the use of HIPEC in nonmetastatic patients who are treated with perioperative chemotherapy and radical surgery. The aim of this study was to investigate the putative survival benefit of HIPEC in the subgroup of gastric cancer patients treated with perioperative chemotherapy and surgery. PATIENTS AND METHODS This was a retrospective cohort study that included gastroesophageal junction and gastric cancer patients who were treated with perioperative chemotherapy and curative resection in a single cancer center in the period between 2006 and 2017. In this time period, younger patients with diffuse-type tumors and serosa invasion or positive lymph node disease were often offered an adjuvant HIPEC protocol. This study compared the survival outcomes of these patients to the ones of those who received only perioperative chemotherapy and resection. A 2:1 propensity-score matched analysis for the two groups was also performed, and variables used were postchemotherapy T (ypT) and N (ypN) stages, histology and tumor site. RESULTS The study population comprised 269 subjects, 241 treated with chemotherapy and surgery and 28 who also received HIPEC. The mean age was 59 years old (standard deviation: 12.2) and 60% of all individuals were male. A total gastrectomy was performed in 137 patients and a distal resection in 132, with a D2-lymphadenectomy in 97.4% of the sample. Overall 60-day morbidity and mortality rates were 35.3% and 3.3%, respectively. In the HIPEC group, patients were younger, and more frequently had American Society of Anesthesiologists (ASA) 1 to 2 classification, tumors located in the gastric body, had diffuse histology, and ypN+ disease. Overall survival (OS; 5 years) results in the HIPEC and no HIPEC group were 59.5% vs 68.7% (P = .453), and disease-free survival (DFS) ones were 49.5% and 65.8% (P = .060), respectively. In the multivariable Cox regression model, ypT and ypN were independent overall and DFS predictors; also, ASA 3 to 4 classification and diffuse histology were associated with worse OS. In the matched analysis, HIPEC did not improve either overall (53.5% vs 59.5%; P = .517) or DFS (50.0% vs 49.5%; P = .993). CONCLUSION Treatment with HIPEC in patients who received perioperative chemotherapy and a D2-resection did not improve survival outcomes. Both ypT and ypN stages remained as the most important survival predictors in this cohort.
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Affiliation(s)
| | - Wilson L da Costa
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil.,Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | | | - Héber S C Ribeiro
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Alessandro L Diniz
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - André Luís de Godoy
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | | | - Silvio Melo Torres
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Tiago C Felismino
- Department of Clinical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil
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19
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The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas. Am J Clin Oncol 2019; 41:1176-1184. [PMID: 29672365 DOI: 10.1097/coc.0000000000000447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ(2) analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. RESULTS The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. CONCLUSIONS Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.
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20
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Bouabdallah I, Thomas PA, D'Journo XB. Recurrence in complete responders after trimodality therapy in esophageal cancer. J Thorac Dis 2019; 11:S1304-S1306. [PMID: 31245116 DOI: 10.21037/jtd.2019.04.77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Ilies Bouabdallah
- Department of Thoracic Surgery, North Hospital, Aix-Marseille University, CNRS, INSERM, CRCM, AP-HM, Chemin des Bourrely, 13915 Marseille, France
| | - Pascal Alexandre Thomas
- Department of Thoracic Surgery, North Hospital, Aix-Marseille University, CNRS, INSERM, CRCM, AP-HM, Chemin des Bourrely, 13915 Marseille, France
| | - Xavier Benoit D'Journo
- Department of Thoracic Surgery, North Hospital, Aix-Marseille University, CNRS, INSERM, CRCM, AP-HM, Chemin des Bourrely, 13915 Marseille, France
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21
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Heger U, Sisic L, Nienhüser H, Blank S, Hinz U, Haag GM, Ott K, Ulrich A, Büchler MW, Schmidt T. Neoadjuvant Therapy Improves Outcomes in Locally Advanced Signet-Ring-Cell Containing Esophagogastric Adenocarcinomas. Ann Surg Oncol 2018; 25:2418-2427. [PMID: 29855828 DOI: 10.1245/s10434-018-6541-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Only a few studies have analyzed multimodal treatment concepts in the subgroup of signet-ring-cell containing upper gastrointestinal (GI) cancer. Recent retrospective, multicentric data favor primary resection without neoadjuvant chemotherapy for gastric signet-ring-cell containing carcinomas (SRCs). We compared the outcomes of primarily resected carcinomas with neoadjuvantly treated, locally advanced esophagogastric SRCs. METHODS A total of 310 patients with esophagogastric SRC-staged cT3/4/Nany/Many from a prospective unicentric database were included in this study; 192 (61.9%) received neoadjuvant therapy (NEO group) and 118 (38.1%) were primarily resected (RES group). RESULTS Overall, 128 (41.3%) patients presented with adenocarcinoma of the esophagogastric junction (AEG) and 182 (58.7%) presented with gastric cancer. Neoadjuvant therapy was significantly associated with resection in curative intent (NEO: 91.1%; RES: 75.4%; P = 0.001), improved (y)pT category (P = 0.035), improved (y)pN category (P < 0.001), and R0 resections (curative intent cohort: 76.0% in NEO vs. 60.7% in RES; P = 0.010), among others, but not with postoperative complications. Overall survival was significantly improved by neoadjuvant treatment {median survival 28.5 months (95% confidence interval [CI] 14.4-39.6) vs. RES: 14.9 months (10.6-17.5); P < 0.001}, as well as in subgroups (AEG and gastric tumors, R0-resected patients, and patients with and without relevant comorbidities). Independent prognostic factors were neoadjuvant therapy (hazard ratio [HR] 0.66; P = 0.023), pT4 category (HR 1.71; P = 0.041), pN2 category (HR 1.86; P = 0.013), pN3 category (HR 2.40; P < 0.001), pM1 category (HR 1.95; P = 0.003), age > 70 years (HR 1.79; P = 0.006), gastric localization (HR 0.69; P = 0.032), American Society of Anesthesiologists classification 3/4 (HR 1.71; P = 0.004), and incomplete resection R1/2 (HR 1.6; P = 0.014). CONCLUSIONS Our results demonstrate a survival advantage for advanced-stage esophagogastric SRC patients by neoadjuvant treatment.
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Affiliation(s)
- Ulrike Heger
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Leila Sisic
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Henrik Nienhüser
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Susanne Blank
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Georg Martin Haag
- National Center for Tumor Diseases (NCT), University Hospital, Heidelberg, Germany
| | - Katja Ott
- Department of Surgery, RoMed Klinikum, Rosenheim, Germany
| | - Alexis Ulrich
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany.
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22
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Abstract
In the World Health Organization (WHO) classification, adenocarcinoma of esophagus comprises preinvasive type (dysplasia), adenocarcinoma, adenoid cystic carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. For adenocarcinoma, it is important to determine the grading of the cancer and histological variants such as signet ring adenocarcinoma. In the current day management of esophageal adenocarcinoma by neoadjuvant therapy, the histology of the cancer and the lymph nodal status may change after the therapy. Tumor regression grading systems could be used to assess the response to the neoadjuvant therapy in esophageal adenocarcinoma.
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Affiliation(s)
- Alfred K Lam
- Cancer Molecular Pathology of School of Medicine, Griffith University, Gold Coast, Australia.
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23
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Bleaney CW, Barrow M, Hayes S, Ang Y. The relevance and implications of signet-ring cell adenocarcinoma of the oesophagus. J Clin Pathol 2017; 71:201-206. [PMID: 29212656 DOI: 10.1136/jclinpath-2017-204863] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 11/15/2017] [Accepted: 11/16/2017] [Indexed: 12/20/2022]
Abstract
AIM To review the current understanding of signet-ring type oesophageal adenocarcinoma including evidence for prognosis. METHODS We conducted a literature search of nine healthcare literature databases for articles detailing the biology and clinical outcomes of signet-ring cell adenocarcinoma of the oesophagus. The impact of signet-ring cell morphology was analysed and detailed in written text and tabular format. Current understanding of the biology of signet-ring cell adenocarcinoma of the oesophagus was summarised. RESULTS Signet-ring cell carcinoma was represented in 7.61% of the 18 989 cases of oesophageal carcinoma reviewed in multiple studies. The presence of signet-ring cells conferred a worse prognosis and these tumours responded differently to conventional treatments as compared with typical adenocarcinoma. Little is known about the biological features of signet-ring cell adenocarcinoma of the oesophagus. Work in gastric lesions has identified potential targets for future treatments such as CDH1 and RHOA genes. Categorisation of signet-ring cell carcinomas by the proportion of signet-ring cells within tumours differs among clinicians despite WHO criteria for classification. The current UK guidelines for histopathological reporting of oesophageal tumours do not emphasise the importance of identifying signet-ring cells. CONCLUSION The presence of signet-ring cells in oesophageal adenocarcinomas leads to poorer clinical outcomes. Current understanding of signet-ring cell biology in oesophageal cancer is limited.
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Affiliation(s)
| | - Mickhaiel Barrow
- Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, UK
| | - Stephen Hayes
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Department of Histopathology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Yeng Ang
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Department of Gastroenterology, Salford Royal NHS Foundation Trust, Salford, UK
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24
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Chen L, Liu X, Gao L, Wang R, Gao D, Bai D. The clinicopathological features and prognosis of signet ring cell carcinoma of the esophagus: A 10-year retrospective study in China. PLoS One 2017; 12:e0176637. [PMID: 28486494 PMCID: PMC5423587 DOI: 10.1371/journal.pone.0176637] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Accepted: 04/13/2017] [Indexed: 12/14/2022] Open
Abstract
Objectives The aim of this study was to analyze the clinicopathological features and prognosis of esophageal signet ring cell (SRC) carcinoma in China. Methods Patients with poorly differentiated adenocarcinoma were identified in two hospitals from January 2006 to June 2016. The patients were divided into three groups according to component of SRCs: SRC≥50% group, SRC < 50% group and non-SRC poorly differentiated adenocarcinoma group. Results Fifty-seven patients had carcinoma (SRC≥50%), and 79 patients had tumors containing <50% SRCs, and 535 patients was in non-SRC poorly differentiated adenocarcinoma group. There were no significant differences among the three groups in clinicopathological characteristics. Patients in SRC≥50% group had a lower overall survival rate (at 3-year 37.6%versus71.1%; at 5-year 0% versus 43.3%; p<0.001) compared with the control group. Even survival outcome of patients in SRC < 50%was inferior to that of in control group (at 3-year 53.0%versus71.1%; at 5-year 25.9% versus 43.3%; p<0.001). Female sex, large tumor size and increasing TNM stage were independent prognostic factors for SRC ≥50% esophageal carcinoma patients. Conclusions The incidence of esophageal SRC carcinoma is relatively rare and the worst outcome is observed in the SRC≥ 50% group. It is necessary to explore new therapeutic modalities to achieve further improvements in the clinical outcome of these patients.
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Affiliation(s)
- Lei Chen
- Department of Thoracic Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Xi Liu
- Department of Thoracic Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Linggen Gao
- Department of Comprehensive Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Rong Wang
- Department of Comprehensive Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China
| | - Dewei Gao
- Department of Comprehensive Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China
- * E-mail: (DG); (DB)
| | - Dongyu Bai
- Department of Pathology, the First Affiliated Hospital of Xiamen University, Province Fujian, Xiamen, China
- * E-mail: (DG); (DB)
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25
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Is signet-ring cell carcinoma a specific entity among gastric cancers? Gastric Cancer 2016; 19:1027-1040. [PMID: 26606931 DOI: 10.1007/s10120-015-0564-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 11/02/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognosis and chemoresistance of signet-ring cell (SRC) gastric adenocarcinoma have been reported and debated, and the utility of perioperative chemotherapy for such a tumor has been questioned . This study was performed to assess the impact of the SRC type on survival following resection of gastric adenocarcinoma, and to assess whether the prognostic factors (including perioperative chemotherapy) for non-SRC adenocarcinoma differed from those for SRC adenocarcinoma. METHODS 1799 cases of adenocarcinoma that were consecutively treated from 1997 to 2010 in 19 French centers by subtotal or total gastrectomy were included in a retrospective study. A D2 lymphadenectomy was performed for antropyloric tumors, and a modified D2 for upper tumors. SRC adenocarcinoma was diagnosed based on the presence of isolated carcinoma cells containing mucin. RESULTS A total gastrectomy was performed in 979 (54.4 %) patients. SRC adenocarcinoma was diagnosed in 899 (50 %) patients. Patients with an SRC tumor were more frequently female, younger, and malnourished, had lower ASA scores, and had larger tumors than non-SRC patients. Median survival in patients with non-SRC carcinoma was 51 months, as compared to 26 months in patients with SRC carcinoma (p < 0.001). At multivariate analysis, SRC type remained an independent adverse prognostic factor (HR = 1.182). Factors that were prognostic in the SRC subgroup but not in the non-SRC subgroup were age >60 years, linitis, and involvement of adjacent organs. In contrast to non-SRC tumors, pre- and postoperative chemotherapy did not significantly impact on survival following resection of SRC adenocarcinoma. CONCLUSION In comparison to non-SRC adenocarcinoma, the SRC type has a worse prognosis, different prognostic factors, and is only poorly sensitive to perioperative chemotherapy. Non-SRC and SRC adenocarcinomas should be considered different entities in future therapeutic trials.
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26
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Turner KO, Genta RM, Sonnenberg A. Oesophageal signet ring cell carcinoma as complication of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2015; 42:1222-31. [PMID: 26345286 DOI: 10.1111/apt.13395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 07/28/2015] [Accepted: 08/16/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Signet ring cell carcinoma occurs as a histological variant of oesophageal adenocarcinoma. AIM In a cross-sectional study, to pursue the hypothesis that oesophageal signet ring cell cancers constitute a complication of gastro-oesophageal reflux disease. METHODS In a large national database of histopathology records, we accumulated 91 802 patients with Barrett's oesophagus (BE), 2817 with oesophageal nonsignet ring adenocarcinoma (EAC) and 278 with oesophageal signet ring cell carcinoma (SRC). The three groups were compared with respect to their clinical and demographic characteristics, as well as socio-economic risk factors (associated with patients' place of residence). RESULTS About 9% of all oesophageal adenocarcinomas harboured features of signet ring cell carcinoma. Patients with oesophageal adenocarcinoma and signet ring cell carcinoma were characterised by almost identical epidemiological patterns. Patients with either cancer type were slightly older than those with Barrett's oesophagus (EAC 68.0, SRC 66.7 vs. BE 63.7 years), and both showed a striking male predominance (EAC and SRC 85% vs. BE 67%). Both cancer types were associated with a similar set of alarm symptoms, such as dysphagia, pain and weight loss. The distribution by race (Whites vs. Blacks) and socio-economic parameters, such as levels of college education and family income, were similar among the three groups of patients. CONCLUSIONS Signet ring cell carcinoma is a rare variant of oesophageal adenocarcinoma with similar epidemiological characteristics. The reasons why a minority of reflux patients progress to develop signet ring cell carcinoma, rather than the usual type of oesophageal adenocarcinoma, remain unknown.
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Affiliation(s)
- K O Turner
- Miraca Life Sciences Research Institute, Irving, TX, USA.,University of Texas Southwestern Medical Center College of Medicine, Dallas, TX, USA
| | - R M Genta
- Miraca Life Sciences Research Institute, Irving, TX, USA.,University of Texas Southwestern Medical Center College of Medicine, Dallas, TX, USA.,VA Medical Center, Dallas, TX, USA
| | - A Sonnenberg
- Oregon Health & Science University, Portland, OR, USA.,VA Medical Center, Portland, OR, USA
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