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Purpose To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. Methods Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. Results One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). Conclusions Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results. [ABSTRACT FROM AUTHOR]

Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision., Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg., Results: Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively)., Conclusion: Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer., Methods: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry., Results: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively)., Conclusions: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC., (© 2024 American Cancer Society.)

Background: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer., Methods: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series., Results: In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8β expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa., Conclusion: Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: Prognostic Nutritional Index (PNI) is a useful tool to predict short-term results in patients undergoing surgery for gastrointestinal cancer. Few studies have addressed this issue in colorectal cancer or specifically in rectal cancer. We evaluated the prognostic relevance of preoperative PNI on morbidity of patients undergoing laparoscopic curative resection for rectal cancer (LCRRC)., Methods: PNI data and clinico-pathological characteristics of LCRRC patients (June 2005-December 2020) were evaluated. Patients with metastatic disease were excluded. Postoperative complications were evaluated using the Clavien-Dindo classification., Results: A total of 182 patients were included in the analysis. Median preoperative PNI was 36.5 (IQR 32.8-41.2). Lower PNI was associated with females (p=0.02), older patients (p=0.0002), comorbidity status (p<0.0001), and those who did not receive neoadjuvant treatment (p=0.01). Post-operative complications occurred in 53 patients (29.1%), by the Clavien-Dindo classification: 40 grades I-II and 13 grades III-V. Median preoperative PNI was 35.0 (31.8-40.0) in complicated patients and 37.0 (33.0-41.5) in uncomplicated patients (p=0.09). PNI showed poor discriminative performance regarding postoperative morbidity (AUC 0.57) and was not associated with postoperative morbidity (OR 0.97) at multivariable analysis., Conclusions: Preoperative PNI was not associated with postoperative morbidity after LCRRC. Further research should focus on different nutritional indicators or hematological/immunological biomarkers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach., (© 2022. Italian Society of Surgery (SIC).)

Purpose: Left hemicolectomy is the standard surgical operation for a variety of colonic diseases, both benign and malignant. When colonic resection is extended, relocation of the small bowel loops can be difficult. Several techniques have been described to reposition the small intestine. Welti's technique consists in the passage of the entire small bowel to the left side of the abdomen, below the descending colon that is positioned on the right side. Methods: We retrospectively evaluated 23 patients who underwent extended left hemicolectomy and reconstruction according to the Welti's technique at our hospital. We assessed the recovery of intestinal function and the length of hospital stay; in the mid-term follow-up we searched for episodes of acute or chronic intestinal obstruction. Results: Median operative time was 215 minutes; median resumption of gas and stool emission were, respectively, 3 days (interquartile range [IQR]: 2-6) and 4 days (IQR: 2-9) after surgery. Median hospital stay was 8 (IQR: 5-37) day. After a median follow-up of 15 months (IQR: 3-132) we did not observe any episode of acute or chronic bowel obstruction. Conclusions: Welti's technique is safe and does not cause a delay in resumption of bowel functions or a delayed hospital discharge; it is a useful technique that the colorectal surgeon can use when needed.

Background: Studies evaluating sex differences in colorectal cancer (CRC) tumor microenvironment are limited, and no previous study has focused on rectal cancer patients' constitutive immune surveillance mechanisms. The authors aimed to assess gender-related differences in the immune microenvironment of rectal cancer patients., Methods: A systematic review and meta-analysis were conducted up to 31 May 2021, including studies focusing on gender-related differences in the CRC tumor microenvironment. Data on the mutational profile of rectal cancer were extracted from the Cancer Genome Atlas (TCGA). A subanalysis of the two IMMUNOREACT trials (NCT04915326 and NCT04917263) was performed, aiming to detect gender-related differences in the immune microenvironment of the healthy mucosa in patients with early (IMMUNOREACT 1 cohort) and locally advanced rectal cancer following neoadjuvant therapy (IMMUNOREACT 2 cohort). In the retrospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 442 patients (177 female and 265 male), while in the retrospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), we enrolled 264 patients (80 female and 184 male). In the prospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 72 patients (26 female and 46 male), while in the prospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), the authors enrolled 105 patients (42 female and 63 male)., Results: Seven studies reported PD-L1 expression in the CRC microenvironment, but no significant difference could be identified between the sexes. In the TGCA series, mutations of SYNE1 and RYR2 were significantly more frequent in male patients with rectal cancer. In the IMMUNOREACT 1 cohort, male patients had a higher expression of epithelial cells expressing HLA class I, while female patients had a higher number of activated CD4+Th1 cells. Female patients in the IMMUNOREACT 2 cohort showed a higher infiltration of epithelial cells expressing CD86 and activated cytotoxic T cells (P=0.01)., Conclusions: Male patients have more frequent oncogene mutations associated with a lower expression of T-cell activation genes. In the healthy mucosa of female patients, more Th1 cells and cytotoxic T cells suggest a potentially better immune response to the tumor. Sex should be considered when defining the treatment strategy for rectal cancer patients or designing prognostic scores., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Agenesis of the gallbladder (AGB) without extrahepatic biliary atresia is a rare congenital disease. Ultrasound (US) examination can be misleading and reveal a contracted shrunken gallbladder when there is not any and the patient in most cases is taken to the OR for a standard cholecystectomy. We describe the case of a 54-year-old female with colicky right upper abdominal pain with nausea. US revealed a contracted scleroatrophic gallbladder and the patient was listed for laparoscopic cholecystectomy. At laparoscopy, despite careful search, the gallbladder was never visualised, and the suspicion of AGB was raised. An intra-operative cholangiography confirmed the hypothesis. The post-operative recovery was uneventful, and abdominal computed tomography scan failed to show the presence of gallbladder, therefore confirming the diagnosis of AGB. Lack of awareness of this condition among radiologists and surgeons is the main reason for unnecessary operations and potentially damages to the biliary tract., Competing Interests: None

Background: Infra-ampullary duodenal lesions are rare and surgical management is controversial. The commonly accepted treatment, which allows radical resection, is pancreaticoduodenectomy, but segmental duodenal resection has been considered as alternative. Aim of the study was to describe the effectiveness of minimally invasive resection of the third/fourth portion of the duodenum for both benign and malignant lesions, with pancreas preservation and reconstruction through end-to-side duodenojejunostomy. Methods: Data from patients undergoing elective laparoscopic curative duodenal resection with pancreas preservation between June 2005 and June 2019 were prospectively collected. Results: A total of 5 patients were identified (3M/2F), median age 73 years (range: 54-83). Lesions were all located in the third or fourth portion of the duodenum and were adenocarcinoma in 2 patients (pT2N0 and pT3N2, both 3 cm in diameter) and gastrointestinal stromal tumor in 3 patients (two pT1N0 and one pT2N0, low-risk according to Miettinen, of 3, 2, and 5 cm in diameter, respectively). The operations lasted a median of 225 minutes (range: 180-300). Digestive continuity was restored with fully laparoscopic side-to-side duodenojejunostomy in all cases. One patient developed pneumonia after surgery (20%) and required also postoperative blood transfusions. Reoperation and mortality rate was nil. Median postoperative stay was 11 days (range: 10-13). The median follow-up was 30 months. Conclusions: Fully laparoscopic pancreas-preserving duodenal resection with duodenojejunal reconstruction can be a safe and feasible option for both benign and malignant lesions of the third and fourth portion of the duodenum. It brings good oncological results, but it needs to be validated with larger number of patients.

Background: Internal hernia (IH) after laparoscopic colorectal surgery is a potentially severe complication. It may go undiagnosed in patients having their abdominal CT scan during oncologic follow-up. We evaluated the occurrence of IH on CT scans after laparoscopic curative resection for rectal cancer (LRRC) and routine closure of the mesenteric defect., Methods: Data from 189 consecutive patients undergoing elective curative LRRC in a 14-year period (June 2005-june 2019) were prospectively collected. Only patients with abdominal CT scans, performed as routine oncologic follow-up, between 3 months and 7 years post-operatively were included in the study and reviewed by a surgeon and a radiologist., Results: A total of 161 patients were eligible for the study with a median age of 69 years (IQR: 59-77) at surgery. They had abdominal follow-up CT scans at a median of 39.5 months (IQR: 12.8-62.7) after surgery. The prevalence of IH was 11.2% (18/161 patients). Of the 18 patients, 15 (83.3%) were fully asymptomatic, 2 (11.1%) reported chronic abdominal discomfort (including mostly nausea and colicky pain) during their oncologic follow-up (however, IH was not suspected neither prompted additional investigations), and 1 (5.6%) was reoperated elsewhere for IH and acute small bowel obstruction., Conclusions: IH following LRRC is not uncommon, with a prevalence > 10% in our experience. Most of these patients remain fully asymptomatic, but in a few patients, IH might be responsible for some symptoms or require reoperation. Awareness of this complication is important, given the potential risk of acute small bowel obstruction., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Laparoscopic and thoracoscopic surgery often require extraction of surgical specimens. The use of standard retrieval bag can be expensive, especially in case of multiple specimens during the same operation. We describe the use of a folded glove-finger as cheap alternative and easily reproducible means of specimen extraction. The medium finger of a glove, cut at its base, was used to locate several types of specimens. The edge of the glove was folded to allow an easier insertion and retrieval of the specimens. Using this technique in the last 5 years, we have retrieved hundreds of different types of specimens (including omentum, lymph nodes, appendix, peritoneal or pleural biopsies) during laparoscopic and thoracoscopic procedures. All the retrieval fingers were safely pulled outside and were intact when extracted through the ports with no fragmentation of the specimens. In conclusion, we suggest that a folded glove-finger can be used as an easy, quick and cheap strategy for specimen extraction during laparoscopic and thoracoscopic surgery.

Background: There are few reports comparing safety and efficacy of 2-D and 3-D video technology in laparoscopic right hemicolectomy. The aim of the study was to assess the short-term results of laparoscopic right hemicolectomy (LHR) with intracorporeal anastomosis with 2-D/3-D video in patients with right colon cancer., Methods: Data from 239 patients undergoing LRH for cancer in a 14-year period (June 2005-January 2020) were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons., Results: One hundred and fourteen patients were included in the study: 55 (48.2%) operated with 2-D and 59 (51.8%) with 3-D video. Tumor site and postoperative stage distribution were similar. Mean operative time was comparable in the two groups (159.0 ± 48.8 min vs. 17.06 ± 36.0 min, p = ns, group 2-D and 3-D, respectively). Group 3-D patients had a similar percentage of associated procedures (44.1% vs. 29.1%, p = ns). Intraoperative complications were nil in both groups, while postoperative complications were similar (30.9% 2-D vs 25.4% 3-D, p = ns). The mean number of lymph nodes retrieved was similar in group 3-D (26.0 ± 14.6 vs. 22.9 ± 9.3, p = ns) and the length of stay was comparable in 3-D and 2-D patients (8.4 ± 2.6 vs. 9.1 ± 3.3 days, respectively, p = ns)., Conclusions: Laparoscopic 3-D vision is as equally effective as 2-D vision in LRH with intracorporeal anastomosis, with a similar proportion of associated procedures and number of lymph nodes retrieved in the same operative time. Further prospective larger randomized studies are necessary to verify if LRH with 3-D video can reduce postoperative complications, compared to 2-D video., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

We developed a new technique to reduce the length of the enteric defect to be closed during intracorporeal anastomosis in laparoscopic right hemicolectomy (LRH), also avoiding the need to suture the first part of the anastomosis in a deep space with an acute angle. From January 2017, after the ileo-colic anastomosis was completed, an additional stapler cartridge was applied starting at the colonic rim and including the small bowel part of the anastomosis. The isoperistaltic fashion of the ileo-colonic anastomosis was maintained. The remaining defect left to be closed was 2-3 cm. We compared the results of the novel technique with those of the 'standard' closure (full-length enterotomy). In the last 30 months, this technique was successfully used in 32 patients (Group A), compared with 33 patients (2012-2016) operated with 'standard' closure (Group B). Age, BMI and post-operative stage distribution were similar. The mean operative time was 175.2 min (± 36.7) in Group A and 165.9 min (± 42.5) in Group B (p = ns), with 53.1% and 27.3% of associated procedures (cholecystectomy, ovariectomy, etc.), respectively (p < 0.05). Overall morbidity rate was 28.1% and 30.3% (Group A vs Group B, p = ns), with no anastomotic bleeding/leak in either group. This technique, which simplifies the closure of the enteric defect after LRH with intracorporeal anastomosis is safe, reproducible and easy to learn. It might help more surgeons to perform a fully laparoscopic procedure in right hemicolectomy, offering the advantages of intracorporeal anastomosis to their patients., (© 2021. Italian Society of Surgery (SIC).)

Background: Internal hernia (IH) is an infrequent complication following colorectal resection with minimally invasive technique. The real prevalence is difficult to define and there are only few large series reporting data on this complication, often focusing only on left-sided resections. Aim of the study was to evaluate the occurrence of IH following laparoscopic colorectal resection (LCR), reporting clinical presentation and treatment., Methods: Data from 1297 patients undergoing elective LCR for cancer or benign disease in a 15-year period (June 2005-March 2020) were prospectively collected. A database query was performed to search for small bowel obstructions requiring reintervention., Results: Five patients presented symptomatic IH (prevalence = 0.38%) and required reintervention. The preceding surgical procedure was left hemicolectomy for diverticular disease in all patients. The mesenteric defect had been originally closed in 4/5 patients. The median time interval between initial surgery and the occurrence of IH was 1 (range: 0.3-10) month. In all cases a small bowel loop was found herniating through the mesocolic defect. Small bowel resection was required in one patient only. The median hospital stay following reintervention was 7 (range: 4-17) days., Conclusions: IH following LCR is a rare but severe complication, potentially leading to death, if not promptly diagnosed and treated. Awareness of this complication, early recognition, and proper diagnostic and therapeutic management is mandatory allowing laparoscopic approach and often avoiding small bowel resection.

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.

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 1.72-11.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04-31.4, 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.

Background: The aim of this study is to compare surgical outcomes including postoperative complications and prognosis between total gastrectomy (TG) and proximal gastrectomy (PG) for proximal gastric cancer (GC). Propensity-score-matching analysis was performed to overcome patient selection bias between the two surgical techniques., Methods: Among 457 patients who were diagnosed with GC between January 1990 and December 2010 from four Italian institutions, 91 underwent PG and 366 underwent TG. Clinicopathologic features, postoperative complications, and survivals were reviewed and compared between these two groups retrospectively., Results: After propensity-score matching had been done, 150 patients (75 TG patients, 75 PG patients) were included in the analysis. The PG group had smaller tumors, shorter resection margins, and smaller numbers of retrieved lymph nodes than the TG group. N stages and 5-year survival rates were similar after TG and PG. Postoperative complication rates after PG and TG were 25.3 and 28%, respectively, (P = 0.084). Rates of reflux esophagitis and anastomotic stricture were 12 and 6.6% after PG and 2.6 and 1.3% after TG, respectively (P < 0.001 and P = 0.002). 5-year overall survival for PG and TG group was 56.7 and 46.5%, respectively (P = 0.07). Survival rates according to the tumor stage were not different between the groups. Multivariate analysis showed that type of resection was not an independent prognostic factor., Conclusion: Although PG for upper third GC showed good results in terms of survival, it is associated with an increased mortality rate and a higher risk of reflux esophagitis and anastomotic stricture.

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 + hepatic 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 < 0.001) 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.

According to the more recent European guidelines, the D2 lymphadenectomy is considered the standard for curative intent treatment of patients with gastric cancer. Although, the surgical definition of D2 dissection and its technical aspects had been learned from Eastern surgeons in the past decades, some variations in the approach to D2 lymphadenectomy by European surgeons were detectable in randomized clinical trials dealing with lymphadenectomy. Despite in more recent years an improvement in surgical quality has been reported in European series, some differences in the practice of D2 dissection are thought to persist. As, these may contribute to discrepancies in gastric cancer survival observed across European countries, the standardization of surgical quality is an urgent need to improve the outcome of gastric cancer patients in Europe. In this manuscript, we focus on the technical aspects of the D2 dissection both in open and laparoscopic gastrectomy in order to contribute to the improvement of surgical care of gastric cancer in the West., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Resection margin (RM) involvement is associated with negative prognosis after gastrectomy. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time-consuming and resource-consuming. The aim of this study was to assess risk factors associated with RM involvement to identify patients who would benefit from IFS analysis., Methods: We retrospectively analyzed patients who underwent gastrectomy with curative intent for gastric or esophagogastric junction (EGJ) cancer from 2000 to 2014 in six Italian hospitals. RM status was assessed by IFS analysis and/or definitive histopathology examination. A set of 21 potential risk factors were compared in a multivariate analysis between patients with positive RMs on IFS analysis or definitive histopathology examination and a control cohort of similar patients with negative RMs, with the samples stratified into three subgroups (T1, T2-T4 Lauren intestinal pattern, T2-T4 Lauren diffuse/mixed pattern)., Results: One hundred forty-five patients had positive RMs. Survival was significantly worse in positive RM patients than in negative RM patients (89.5 months vs 28.9 months). Multivariate analysis showed that in T1 cancers a margin distance of less than 2 cm is a risk factor for RM involvement (odds ratio 15.7), in T2-T4 intestinal pattern cancers, serosa invasion (odds ratio 6.0), EGJ location (odds ratio 4.1), and a margin distance of less than 3 cm (odds ratio 4.0) are independent risk factors, and in T2-T4 diffuse/mixed pattern cancers, lymphatic infiltration (odds ratio 4.2), tumor diameter greater than 4 cm (odds ratio 3.5), EGJ location (odds ratio 2.8), and serosa invasion (odds ratio 2.2) are independent risk factors., Conclusions: Survival after gastrectomy is negatively affected by positive RMs. IFS analysis should be routinely used in patients with a high risk of positive RMs, especially in diffuse pattern cancers.

Background: In case of Krukenberg tumor (KT) of gastric origin it is controversial and debated whether radical surgery in case of synchronous KT or metastasectomy in case of metachronous ones is associated with additional benefits. Role of perioperative treatments is unclear., Methods: Among 2515 female patients who were diagnosed with gastric cancer between January 1990 and December 2012 from 9 Italian centers, 63 presented simultaneously or developed KT as recurrence., Results: Thirty patients presented with synchronous KT, while 33 developed metachronous ovarian metastases during follow-up. The differences between the two groups were analyzed and compared. The median age of 63 patients was 48.0 years (range 31-71). Resection was possible in 53 patients (20 synchronous and 33 metachronous). Twelve patients in the synchronous group and 15 patients of the metachronous group underwent hyperthermic intraperitoneal chemotherapy after resection of KT. All of them underwent adjuvant chemotherapy after KT resection. The median survival for all population was 23 months (95 % confidence interval, 7-39 months). The median survival time in the metachronous group was 36 months, which was significantly longer than that in the synchronous group, 17 months, p < 0.0001., Conclusions: KT remains a clinical challenge for gastric cancer therapy. The extent of disease and feasibility of removal of the metastatic lesion must be carefully evaluated prior to surgery to define the patients group who could benefit most from a resection associated with perioperative treatments.

Purpose: Management of patients with synchronous hepatic metastases as the sole metastatic site at diagnosis of gastric cancer is debated. We studied a cohort of patients admitted to surgical units, investigating prognostic factors of clinical relevance and the results of various therapeutic strategies., Methods: Retrospective multicentre chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors., Results: Forty-four patients received palliative surgery without resection, 98 palliative gastrectomy (in 16 cases associated with R+ hepatectomy), whereas 53 patients received both curative gastrectomy and hepatic resection(s) (R0). Adjuvant chemotherapy was administered to 44 patients. Therapeutic approach was selected on the basis of extension of disease, patient's general conditions and surgeon's attitude. Surgical mortality was 4.6 % and morbidity was 17.4 %. Survival was independently influenced by the factor T of the gastric primary (p = 0.036) and by the degree of hepatic involvement (p = 0.010). T > 2 and H3 liver involvement were associated with worse prognosis with cumulative effect (p = 0.002). Therapeutic approach to the metastases (p = 0.009) and adjuvant chemotherapy (p < 0.001) displayed independent impact upon survival, with benefit for those receiving aggressive multimodal treatment. The 1-, 3-, and 5-year survival rates were 50.4, 14.0, and 9.3 %, respectively, for patients submitted to curative surgery, 16, 8.5, and 4.3 % after palliative gastrectomy, and 6.8, 2.3, and 0 % after palliative surgery without resection., Conclusions: Our data suggest some clinical criteria that may facilitate selection of candidates to curative surgery, which offers the best survival chances, especially when associated with adjuvant chemotherapy.

Importance: The role of multivisceral resection, in the setting of locally advanced gastric cancer, is still debated. Previous studies have reported a higher risk for perioperative morbidity and mortality, with limited objective benefit in terms of survival. Conversely, recent studies have shown the feasibility of enlarged resections and the potential advantage of extended resection for clinical stage T4b gastric adenocarcinoma with good long-term results., Objective: To analyze the role of multivisceral resection for locally advanced gastric cancer with particular attention to the brief and long-term results and to the prognostic value of clinical and pathologic factors., Design: Prospective multicenter study using data from between January 1, 1995, and December 31, 2008., Settings: Seven Italian surgery centers., Patients: A total of 2208 patients underwent curative resections for gastric carcinoma at the centers. Among them, 206 patients presented with a clinical T4b carcinoma. One hundred twelve underwent a combined resection of the adjacent organs with a gastrectomy owing to suspicion or direct invasion of these organs by the gastric cancer., Main Outcomes and Measures: Clinical and pathologic variables were prospectively collected and the feasibility and efficacy of multivisceral resection for locally advanced clinical T4b gastric cancer were assessed., Results: Postoperative mortality and complication rates of patients who underwent a gastrectomy with a combined resection of the involved organs were 3.6% and 33.9%, respectively. Pathologic factors revealed that the nodal involvement was present in about 89.3% of patients and the mean (SD) number of pathologic lymph nodes was 14.8 (16.6). The overall 5-year survival rate was 27.2%. The completeness of resection and lymph node invasion represent independent prognostic parameters at multivariate analysis., Conclusions and Relevance: Our study indicates that patients undergoing extended resections experience acceptable postoperative morbidity and mortality rates, and an en bloc multivisceral resection should be performed in patients when a complete resection can be realistically obtained and when lymph node metastasis is not evident.