Surgical treatment of hepatic metastases from gastric cancer

The purpose of the study was to investigate the clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. We conducted a retrospective multicentre review. We evaluated how survival from surgery was influenced by patient-related, tumour-related and treatment-related prognostic factors. We analysed data on 144 patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting. In 117 cases, an R0 resection was achieved, while in 27 an R\u2009+\u2009hepatic resection was performed. Chemotherapy was administered to 55 patients. Surgical mortality was 2.1% and morbidity 21.5%. One-, 3-, and 5-year OS rates after surgery were 49.9, 19.4 and 11.6%, respectively, with a median OS of 12.0 months. T4 gastric cancer, H3 hepatic involvement, non-curative resection, recurrence after surgery, and abstention from chemotherapy were associated with a worse prognosis. Factor T and H displayed a clear (p\u2009<\u20090.001) cumulative effect. Our data show that R0 resection must be pursued whenever possible. The treatment of T4 gastric cancer with hepatic bilateral and diffuse metastasis (H3) should be considered carefully or it should be probably avoided. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results

Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study

Background: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. Methods: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72\u201311.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04\u201331.4, p = 0.045). Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement

Siewert III esophagogastric junction adenocarcinoma: does TNM 8th save us?

Siewert III cancers were classified as esophageal cancers by the TNM 7th edition (TNM7), while being defined as gastric cancers by the new TNM 8th edition (TNM8). Aim of this study was to compare previous and present TNM classifications of Siewert III. From 2000 to 2015, 309 patients with Siewert III adenocarcinoma were treated at ten high-volume centers, belonging to the GIRCG (Italian Research Group for Gastric Cancer). We retrospectively analyzed overall survival according to TNM classifications: gastric TNM8 was compared with either gastric TNM7 or esophageal TNM7. Median number of lymph nodes harvested was 31 (interquartile range 22-44). Agreement between gastric TNM7 and TNM8 was very good (weighted kappa 92.3%, IC 95% 90.3-94.1%). Accordingly, stage migration was observed in 54 of 309 patients (17.5%), with 12 patients upstaged (3.9%) and 42 downstaged (13.6%). Cox models including either gastric TNM7 or TNM8 achieved similar goodness-of-fit and c-index. Differences were much larger, when shifting from esophageal TNM7 to gastric TNM8: the agreement was much lower (weighted kappa 69.1%, 65.2-73.2%), with 196 of 309 patients (63.4%) downstaging. The corresponding Cox model presented the lowest goodness-of-fit and discrimination ability. Gastric TNM7 and TNM8 were largely superimposable, so that stage migration was minor and prognostic significance was similar. At variance, stage migration was substantial when shifting from esophageal TNM7 to TNM8. Moreover, survival models with esophageal TNM7 presented the worst goodness-of-fit and the lowest discrimination ability. This further supports placing Siewert III among gastric cancers, as done in TNM8

Pathological response and outcome after neoadjuvant chemotherapy with DOC (docetaxel, oxaliplatin, capecitabine) or EOF (epirubicin, oxaliplatin, 5-fluorouracil) for clinical T3-T4 non-metastatic gastric cancer

In this prospective observational study, we sought to compare the efficacy and safety of docetaxel + oxaliplatin + capecitabine (DOC) with epirubicin + oxaliplatin + 5-fluouracil (EOF) as neoadjuvant chemotherapy (NAC) for clinical T3 or T4 non-metastatic gastric cancer (GC) patients

Which gastric cancer patients could benefit from staging laparoscopy? A GIRCG multicenter cohort study

Background: This study aimed to investigate which gastric cancer patients could benefit the most from staging laparoscopy. Methods: A retrospective cohort study was carried out, including 316 (216 cM- and 100 cM+) gastric cancer patients who had undergone staging laparoscopy between 2010 and 2020 in seven GIRCG centers. A model including easily-accessible clinical, biochemical and pathological markers was constructed to predict the risk of carcinomatosis. ROC curve and decision curve analyses were used to verify its accuracy and net benefit. Results: In the cM-population staging laparoscopy could detect 67 cases who had peritoneal carcinomatosis or positive cytology, for a yield of 30.5%. In cM-patients, intestinal type tumors (0.25, 0.12-0.51; p = 0.002), cT4 tumors (2.18, 1.11-4.28; p = 0.023) and cancers of the lower third (0.31, 0.14-0.70; p = 0.004) were associated with the presence of peritoneal carcinomatosis and/or positive cytology. The ROC curve analysis of the model including the three variables showed an AUC of 0.75 (0.68-0.81, p < 0.001). The decision curve analyses showed that the model had a higher net benefit than the treating all strategy between threshold probabilities of 15 and 50%. Conclusions: Staging laparoscopy is a useful tool to address the patient with gastric cancer to the most adequate treatment. In cM-patients the assessment of the location of the tumor, the Lauren's histotype and the cT status may help in providing additional elements in indicating or not the use of staging laparoscopy

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group's analysis

Background The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. Methods It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. Results Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. Conclusion The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers

Which gastric cancer patients could benefit from staging laparoscopy? A GIRCG multicenter cohort study

Background: This study aimed to investigate which gastric cancer patients could benefit the most from staging laparoscopy.Methods: A retrospective cohort study was carried out, including 316 (216 cM-and 100 cM thorn ) gastric cancer patients who had undergone staging laparoscopy between 2010 and 2020 in seven GIRCG centers. A model including easily-accessible clinical, biochemical and pathological markers was constructed to predict the risk of carcinomatosis. ROC curve and decision curve analyses were used to verify its accuracy and net benefit.Results: In the cM-population staging laparoscopy could detect 67 cases who had peritoneal carcino-matosis or positive cytology, for a yield of 30.5%. In cM-patients, intestinal type tumors (0.25, 0.12-0.51; p = 0.002), cT4 tumors (2.18, 1.11-4.28; p = 0.023) and cancers of the lower third (0.31, 0.14-0.70; p = 0.004) were associated with the presence of peritoneal carcinomatosis and/or positive cytology. The ROC curve analysis of the model including the three variables showed an AUC of 0.75 (0.68-0.81, p < 0.001). The decision curve analyses showed that the model had a higher net benefit than the treating all strategy between threshold probabilities of 15 and 50%. Conclusions: Staging laparoscopy is a useful tool to address the patient with gastric cancer to the most adequate treatment. In cM-patients the assessment of the location of the tumor, the Lauren's histotype and the cT status may help in providing additional elements in indicating or not the use of staging laparoscopy.(c) 2022 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Stage IV Gastric Cancer: The Surgical Perspective of the Italian Research Group on Gastric Cancer

Background/Aim: This work explored the prognostic role of curative versus non-curative surgery, the prognostic value of the various localizations of metastatic disease, and the possibility of identifying patients to be submitted to aggressive therapies. Patients and Methods: Retrospective chart review of stage IV patients operated on in our institutions. Results: Two hundred and eighty-two patients were considered; 73.4% had a single metastatic presentation. In 117 cases, a curative (R0) resection of primary and metastases was possible; 75 received a R1 resection and 90 a palliative R2 gastrectomy. Surgery was integrated with chemotherapy in multiple forms: conversion therapy, HIPEC, neo-adjuvant and adjuvant treatment. Median overall survival (OS) of the entire cohort was 10.9 months, with 14 months for the R0 subgroup. There was no correlation between metastasis site and survival. At multivariate analysis, several variables associated with the lymphatic sphere showed prognostic value, as well as tumor histology and the curativity of the surgical procedure, with a worse prognosis associated with a low number of resected nodes, D1 lymphectomy, pN3, non-intestinal histology, and R+ surgery. Considering the subgroup of R0 patients, the variables pT, pN and D displayed an independent prognostic role with a cumulative effect, showing that patients with no more than 1 risk factor can reach a median survival of 33 months. Conclusions: Our data show that the possibility of effective care also exists for Western patients with stage IV gastric cancer

Consequences of the COVID-19 pandemic on the diagnosis and treatment of gastric cancer in referral centers in Italy

Background: The coronavirus pandemic had a major impact in Italy. The Italian health system's re-organization to face the emergency may have led to significant consequences especially in the diagnosis and treatment of malignancies. This study aimed to assess the impact of the pandemic in the diagnosis and treatment of gastric cancer in nine Gruppo Italiano RIcerca Cancro Gastrico (GIRCG) centers. Methods: All patients assessed for gastric adenocarcinoma at nine GIRCG centers between January 2019 and November 2020 were included. Patients were grouped according to the date of "patient 1's" diagnosis in Italy: preCOVID versus COVID. Clinico-pathological and outcome differences between the two groups were analyzed. Results: A total of 632 patients were included in the analysis (205 in the COVID group). The cT4 weighted ratios were higher in 2020 from April to September, with the greatest differences in May, August and September. The cM+ weighted ratio was significantly higher in July 2020. The mean number of gastrectomies had the greatest reduction in March and May 2020 compared with 2019. The median times from diagnosis to chemotherapy, to complete diagnostic work-up or to operation were longer in 2019. The median time from the end of chemotherapy to surgery was 17 days longer in the preCOVID group. Conclusions: A greater number of advanced or metastatic cases were diagnosed after the spread of SARS-CoV-2 infection, especially after the "full lockdown" periods. During the pandemic, once gastric cancer patients were referred to one of the centers, a shorter time to complete the diagnostic work-up or to address them to the best treatment option was required

Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study

BACKGROUND: Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides. METHODS: In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5. FINDINGS: Across the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522–0·737) to 0·836 (0·795–0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752–0·841) to 0·897 (0·513–0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676–0·794) to 0·863 (0·747–0·969) for detection of microsatellite instability and from 0·672 (0·403–0·989) to 0·859 (0·823–0·919) for detection of EBV status. INTERPRETATION: Classifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer. FUNDING: German Cancer Aid and German Federal Ministry of Health