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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.

BackgroundAfter the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.MethodsAll patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received.ResultsA total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a p = 0.742).ConclusionsConversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.

Background: Early Gastric Cancer (EGC) reaches 25% of the gastric cancers surgically treated in some areas of Northeastern Italy and is usually characterized by a good prognosis. However, among EGCs classified according to Kodama’s criteria, Pen A subgroup is characterized by extensive submucosal invasion, lymph node metastases and worse prognosis, whereas Pen B subgroup by better prognosis. The aim of the study was to characterize the differences between Pen A, Pen B and locally advanced gastric cancer (T3N0) in order to identify biomarkers involved in aggressiveness and clinical outcome. Methods: We selected 33 Pen A, 34 Pen B and 20 T3N0 tumors and performed immunohistochemistry of mucins, copy number variation analysis of a gene panel, microsatellite instability (MSI), TP53 mutation and loss of heterozygosity (LOH) analyses. Results: Pen A subgroup was characterized by MUC6 overexpression (p = 0.021). Otherwise, the Pen B subgroup was significantly associated with the amplification of GATA6 gene (p = 0.002). The higher percentage of MSI tumors was observed in T3N0 group (p = 0.002), but no significant differences between EGC types were found. Finally, TP53 gene analysis showed that 32.8% of Pen tumors have a mutation in exons 5–8 and 50.0% presented LOH. Co-occurrence of TP53 mutation and LOH mainly characterized Pen A tumors (p = 0.022). Conclusions: Our analyses revealed that clinico-pathological parameters, microsatellite status and frequency of TP53 mutations do not seem to distinguish Pen subgroups. Conversely, the amplification of GATA6 was associated with Pen B, as well as the overexpression of MUC6 and the TP53mut/LOH significantly characterized Pen A.

This study aimed to investigate which gastric cancer patients could benefit the most from staging laparoscopy.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.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 lt; 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%.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.

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.

Background: To validate a nodal regression system for gastric cancer and to verify its impact on prognosis. Methods: This is an ancillary study which included 47 patients of the GASTRODOC trial. The dedicated pathologists of each Institute were invited to revise all the lymph nodes included in the surgical specimens in order to classify the regression according to the grading system proposed by Tsekrekos et al. The association of the nodal regression system and the clinico-pathological characteristics and prognosis were investigated. Results: According to the classification of Tsekrekos et al., there were 19 (40.4%) patients with grade a, 14 (29.8%) with grade b and 14 (29.8%) with grade c nodal regression. This regression system showed significant statistical associations with pathological N status (p < 0.001), residual tumor classification (p = 0.003) and Becker regression system (p = 0.011). At multivariable analysis only Tsekrekos’ grading regression system was significantly associated with the PFS (HR 10.1, 95% CI 1.3–75.5; p = 0.025). Conclusions: The analyzed nodal regression system is significantly associated with Becker's regression system and it has a strong correlation with prognosis.

Introduction: In a gastric cancer (GC) setting, phase II and III studies refer to an ideal patient population and only describe a specific category of patients. Older patients or those in poorer clinical condition are generally excluded from clinical trials. We aimed to evaluate therapeutic approaches to GC in a real-world setting at our institute (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori [IRST] IRCCS) over a 10-year period. Methods: A total of 621 consecutive patients with GC diagnosed between January 2000 and December 2009 were considered retrospectively. Among these, 573 with available information on stage of disease were included in the analysis. Demographic and clinical data were collected from paper or electronic medical records. Results: During the study period, 343 (59.8%) patients were diagnosed with GC stage 0 to IIIC (M0): of these, 118 patients had a relapse of disease. A total of 230 patients (40.2%) presented with metastatic disease at diagnosis. Older age was associated with less frequent administration of adjuvant chemotherapy (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.83–0.91); interaction between age and period (OR, 1.02; 95% CI, 1.01–1.03) and stage of disease at diagnosis (OR, 7.95; 95% CI, 3.71–17.1) were positively associated with administration of adjuvant chemotherapy. Older age (OR, 0.87; 95% CI, 0.84–0.90) and presence of comorbidity (OR, 0.46; 95% CI, 0.26–0.83) were associated with less frequent administration of palliative chemotherapy, whereas from 2000–2004 to 2005–2009, patients were more frequently treated with palliative chemotherapy overall (OR, 3.70; 95% CI, 2.01–6.81). Conclusions: Our results confirm that resection is the standard surgical approach to GC, and that chemotherapy is not widely used in adjuvant and metastatic settings. Older age and comorbidities are associated with nontreatment.

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.

AIM To analyze the clinicopathological characteristics of patients with both node-negative gastric carcinoma and diagnosis of recurrence during follow-up. METHODS We enrolled 41 patients treated with curative gastrectomy for pT2-4aN0 gastric carcinoma between 1992 and 2010, who developed recurrence (Group 1). We retrospectively selected this group from the prospectively collected database of 4 centers belonging to the Italian Research Group for Gastric Cancer, and compared them with 437 pT2-4aN0 patients without recurrence (Group 2). We analyzed lymphatic embolization, microvascular infiltration, perineural infiltration, and immunohistochemical determination of p53, Ki67, and HER2 in Group 1 and in a subgroup of Group 2 (Group 2bis) of 41 cases matched with Group 1 according to demographic and pathological characteristics. RESULTS T4a stage and diffuse histotype were associated with recurrence in the group of pN0 patients. In-depth pathological analysis of two homogenous groups of pN0 patients, with and without recurrence during long-term follow-up (groups 1 and 2bis), revealed two striking patterns: lymphatic embolization and perineural infiltration (two parameters that pathologists can easily report), and p53 and Ki67, represent significant factors for recurrence. CONCLUSION The reported pathological features should be considered predictive factors for recurrence and could be useful to stratify node-negative gastric cancer patients for adjuvant treatment and tailored follow-up.

The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10&ndash, 50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance, however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition.

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 25months (IQR 9-50). Median overall survival from surgery was 15months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12months 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.

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018, Background: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. Methods: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. Results: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. Conclusion: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Background and aims Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed. Methods A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated. Results A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component ( 10% SRCs) and PC carcinomas not otherwise specified (

// Raefa Abou Khouzam 1 , Chiara Molinari 2 , Samanta Salvi 2 , Monica Marabelli 1 , Valeria Molinaro 1 , Donata Orioli 3 , Luca Saragoni 4 , Paolo Morgagni 5 , Daniele Calistri 2 , Guglielmina Nadia Ranzani 1 1 Department of Biology and Biotechnology, University of Pavia, Pavia, Italy 2 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, Pavia, Italy 4 Pathology Unit, Morgagni-Pierantoni Hospital, Forli, Italy 5 Department of General Surgery, Morgagni-Pierantoni Hospital, Forli, Italy Correspondence to: Guglielmina Nadia Ranzani, email: guglielmina.ranzani@unipv.it Keywords: CDH1 transcripts, digital-PCR quantification, intestinal-type gastric cancer, normal gastric mucosa Received: October 04, 2016 Accepted: November 09, 2016 Published: November 16, 2016 ABSTRACT E-cadherin is a cell-cell adhesion protein encoded by CDH1 tumor-suppressor gene. CDH1 inactivating mutations, leading to loss of protein expression, are common in gastric cancer of the diffuse histotype, while alternative mechanisms modulating E-cadherin expression characterize the more common intestinal histotype. These mechanisms are still poorly understood. CDH1 intron 2 has recently emerged as a cis -modulator of E-cadherin expression, encoding non-canonical transcripts. One in particular, CDH1a , proved to be expressed in gastric cancer cell lines, while being absent in the normal stomach. For the first time, we evaluated by digital PCR the expression of CDH1 and CDH1a transcripts in cancer and normal tissue samples from 32 patients with intestinal-type gastric cancer. We found a significant decrease in CDH1 expression in tumors compared to normal counterparts ( P = 0.001), which was especially evident in 76% of cases. CDH1a was detected at extremely low levels in 47% of tumors, but not in normal mucosa. A trend was observed of having less CDH1 in tumors expressing CDH1a transcript. The majority of tumors with both a decrease in CDH1 and presence of CDH1a also showed a decrease in miR-101 expression levels. On the whole, the decrease of CDH1 transcript, corresponding to the canonical protein, and the presence of CDH1a , corresponding to an alternative isoform, are likely to perturb E-cadherin-mediated signaling and cell-cell adhesion, thus contributing to intestinal-type gastric carcinogenesis.

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18&ndash, 1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2&ndash, 65.8) in arm A and 40.3% (95% CI: 28.9&ndash, 55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3&ndash, 72.2) and 53.9% (95% CI: 35.5&ndash, 69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.

403 Background: Surgical approach to gastric cancer with hepatic metastases is becoming more and more accepted but few information exist concerning the surgical management of gastric cancer with extra-hepatic metastases. With this retrospective study we evaluated if the prognosis is influenced by different metastatic sites and we looked for the presence of prognostic factors. Methods: We analysed 282 patients with gastric cancer and synchronous metastases treated at our Institutions from 2010 to January 2017. We investigated survival performances after surgery according to the site of metastases: peritoneal, haematogenous, hepatic, distant lymph nodes and more than one site. Furthermore, we investigated how survival was influenced by patient-, gastric cancer-, metastases- and treatment-related prognostic factors. Results: Median overall survival was 10.9 months. We found no survival differences according to the site of metastases: median survival was 11.2, 11.6, 9.8, 21.4, 7.0 months for peritoneal, hepatic, lymph-nodal, haematogenous and more than1 site of metastases, respectively (p = 0.797). In all subgroups we observed an interesting number of long-term survivors (peritoneal 14.3% ≥36 months, 7.6% ≥60 months; hepatic 13.0% ≥36 months, 2.2% ≥60 months; lymph nodes 12.5% ≥36 months, 3.1% ≥60 months; > 1 site 18.7% ≥36 months, 1.6% ≥60 months). At multivariate analysis the factors that influenced survival were: number of resected lymph-nodes (p = 0.013), extension of lymphadenectomy (p < 0.001), pN (p = 0.003), curativity (p = 0.032) and histology (p = 0.028). Conclusions: We showed that no differences in overall survival according to site of metastases exist and we suggest that patients in whom a curative resection is possible, should be treated by resection of both gastric cancer and metastases.

Background Early gastric cancer (EGC) generally has a good prognosis. However, the current definition of EGC includes various subgroups of patients with different pathological characteristics and different prognoses, some of whom have aggressive disease with a biological behavior similar to that of advanced carcinoma. Materials and Methods We retrospectively evaluated 1,074 patients with EGC who had undergone surgery between 1982 and 2009. The cumulative incidence function of cancer-specific mortality and competing mortality were estimated using the Fine and Gray method. Results The median follow-up period was 193 months (range 1–324). Five hundred and sixty-two (52.3%) patients died, 96 (8.9%) from EGC. The 5-, 10-, and 15-year cumulative incidence rates for mortality of all causes were 20.5% (95% confidence interval [CI] 18.0–22.9), 37.1% (95% CI 34.7–40.7), and 52.6% (95% CI 49.1–56.0), respectively; for cancer-specific mortality, 6.0% (95% CI 4.5–7.6), 9.9% (95% CI 7.9–11.9), and 11.1% (95% CI 8.8–13.3), respectively; and for mortality of other causes, 14.4% (95% CI 12.1–16.6), 27.2% (95% CI 24.2–30.2), and 41.5% (95% CI 38.1–43.3), respectively. A significant increase in the risk of cancer-specific mortality was observed for lesions >2 cm (adjusted hazard ratio [HR] = 1.44, 95% CI 1.07–1.94), Pen A-type disease (adjusted HR = 1.73, 95% CI 1.15–2.61), and node-positive cancers (adjusted HR = 2.28, 95% CI 1.61–3.21). Conclusion Patients with EGC with tumors >2 cm, Pen A-type disease according to Kodama, or lymph node metastases show a poorer prognosis and an increased risk of cancer-specific mortality. Implications for Practice Early gastric cancer generally has a good prognosis, and some patients can be treated radically by endoscopic resection. However, the current definition of early gastric cancer includes subgroups of patients with an aggressive disease. In particular, patients with lymph node metastases and Pen A-type tumors according to Kodama's classification need a more invasive treatment, such as subtotal or total gastrectomy with an extended D2 lymphadenectomy, plus eventual adjuvant chemotherapy.

BACKGROUND: To investigate the role of Kodama PenA subtype in influencing survival in patients with early gastric cancer (EGC). METHODS: All patients surgically treated for EGC at 7 Italian centers (Forlì, Varese, Siena, Verona, Milan, Rome and Perugia) belonging to the Italian Research Group for Gastric Cancer (GIRCG) from January 1982 and December 2009 were included. RESULTS: PenA patients were 230 (21.5%) while other types were 839 (78.5%). Nodal metastases were more common in PenA (30.7%) than non-PenA (10.4%) EGCs. Among preoperative variables, only age (OR 1.02; 95% CI 1.00-1.03, p = 0.009) and macrotype III (OR 1.95; 95% CI 1.39-2.75, p = 0.0001) were significantly associated with Pen A type. Survival analysis performed on N0 patients demonstrated that only size >2 cm (HR 1.85; 95% CI 1.12-3.05, p = 0.017) and age (HR 1.06; 95% CI 1.03-1.08, p < 0.0001) were independent poor prognostic factor. Among N+ patients age (HR 1.04; 95% CI 1.00-1.07, p = 0.048), number of positive lymph nodes (HR 1.13; 95% CI 1.05-1.20, p = 0.0002) and PenA (HR 4.23; 95% CI 1.70-10.55, p = 0.002) were significantly correlated with poor prognosis at multivariate analysis. CONCLUSIONS: Kodama PenA subtype was the most powerful independent prognostic factor in patients with nodal metastases. Its status should always be investigated in EGCs patients.

The purpose of this retrospective study was to evaluate the incidence and prognostic value of metastases to “posterior” (8p, 12b/p, 13) and para-aortic lymph nodes in a large cohort of Western patients submitted to D2 plus lymphadenectomy. Removal of “posterior” nodes was performed in 743 patients, and para-aortic lymphadenectomy in a subgroup of 390 patients. After lymph node mapping and retrieval on the fresh specimen, a median number of 41 total lymph nodes were analyzed. The median follow-up period was 37 months for the entire series and 68 months for survivors. Of 743 included patients, 23 (3.1%) had metastases in station 8p, 12 (1.6%) in station 12b/p, and 19 (2.6%) in station 13. On the whole, 47 of 743 patients (6.3%) had positive “posterior” nodes. Para-aortic metastases were present in 42 of 390 patients (10.8%). Metastases to “posterior” stations were significantly related to depth of invasion, number of positive nodes, and surgical radicality. Distal tumors showed higher trend to metastasize to “posterior” nodes than upper third, whereas for para-aortic metastases it was the reverse. 5-year survival in patients with positivity to “posterior” nodes was 17%, with no significant difference according to 8p, 12b/p, and 13 stations; long-term outcome was overlapping to pN3b stage. 5-year survival in para-aortic positive cases was 11%, and a trend to better outcome was observed in proximal tumors. Although metastases to “posterior” and para-aortic nodes are expression of an advanced nodal stage, not negligible survival rates are observed in subgroups of patients.

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

BACKGROUND: Surgery has become an important tool for cancer treatment, requiring many available resources and a good organization of the surgery service. The aim of this study was to provide robust data for policymakers on the impact of hospital volume on survival, taking into account different sources of information. METHODS: We performed a retrospective study in a cohort of patients with gastric cancer submitted to partial or total gastrectomy. Data for the analysis were retrieved from regional administrative databases, the regional death registry, and histological reports. The main outcome measures were operative mortality and long-term survival. The associations between hospital volume and risk of mortality were calculated using a Cox multiple regression analysis. RESULTS: The estimated relationship between operative mortality and volume was not statistically significant. Conversely, high-volume hospitals had an increased likelihood of long-term survival compared to low-volume institutions: hazard ratio 0.79 (95 % confidence interval, 0.66-0.94, p = 0.01). The percentage variation between crude and adjusted HRs using only administrative data or administrative and histological data was very small. However, the combined use of administrative and clinical data provided a more accurate model for estimating risk-adjusted mortality. CONCLUSIONS: A positive association between hospital volume and survival was evident for long-term outcome after adjusting for patient and tumor confounding. Moreover, the patient's choice of hospital was not guided by specific care pathways or screening programs, and prognosis was not poorer for patients in high-volume hospitals. These findings suggest that there is leeway for improving access to surgery for gastric cancer patients.

BACKGROUND: Only a few, small, monocentric randomized controlled trials (RCTs) have compared routine vs. no placement of a nasogastric or nasojejunal tube decompression (NG/NJT) in patients undergoing partial distal gastrectomy (PDG) for gastric cancer. However, to our knowledge, no multicenter prospective RCT has analyzed the role of decompression after both the Billroth II (BII) procedure and Roux-en-Y (RY) gastrojejunostomy. The aim of this study was to determine whether NG/NJT prevents the consequences of postoperative ileus after PDG for gastric cancer after both BII reconstruction and RY. METHODS: Two hundred seventy patients undergoing PDG for gastric cancer were randomly assigned NG/NJT placement (NG/NJT group) or not (no-NG/NJT group) with either Billroth II gastrojejunostomy or Roux-en-Y gastrojejunostomy. The patients were monitored for postoperative complications, mortality, and postoperative course. RESULTS: By January 2010 to June 2012, among 270 patients undergoing PDG for gastric cancer, 134 were randomly assigned to NG/NJT placement (NG/NJT group) and 136 to no decompression (no-NG/NJT group). Time to passage of flatus was significantly shorter in the NG/NJT group than in the no-NG/NJT group, but only after RY reconstruction (3.3 ± 1.5 vs. 4.3 ± 1.6 days, P < 0.001, respectively). Postoperative abdominal distention was significantly lower in the NG/NJT group than in the no-NG/NJT group after both BII and the RY procedure (P < 0.001). No significant differences in postoperative mortality or morbidity, especially anastomotic leakage or intra-abdominal sepsis, were observed between the groups. CONCLUSION: Routine placement of an NG/NJT after BII and RY PDG is not necessary in elective surgery for gastric cancer.

Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical-pathological characteristics and prognosis.DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of KIT, exons 12 and 18 of PDGFRA and exons 11 and 15 of BRAF were analyzed by direct sequencing. Cox regression analysis adjusted for clinical-pathological factors was performed to evaluate KIT and PDGFRA mutations in relation to the composite endpoint of relapse or death.KIT and PDGFRA mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and KIT deletions were associated with increased risk of relapse or death (p 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, KIT deletions remained an independent prognostic factor (HRadj = 2.65, 95% CI [1.15-6.13], p = 0.023). Moreover, KIT deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HRadj = 3.29 95% CI [1.64-6.64], p = 0.001).KIT deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death.

Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. On June 19–22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled “Rationale of oncological follow-up after gastrectomy for cancer.” Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years.

Background Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity-related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co-morbid patients. Methods In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. Results Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, pÂ

Background: The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system. Methods: We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006. Results: Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient's age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively). Conclusions: Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer.

The presence of lymph node metastasis is one of the most important prognostic factors in patients with gastric carcinoma. Node-negative patients have a better outcome, nevertheless a subgroup of them experience disease recurrence.To analyze the clinicopathological characteristics of lymph node-negative advanced gastric carcinoma patients submitted to gastrectomy and D2 lymphadenectomy with a retrieved number of nodes greater than 15, after an actual follow-up of almost 5 years, and to evaluate outcome indicators.The records of 301 patients who underwent curative gastrectomy for gastric carcinoma and were adequately staged as N0 between 1992 and 2002 were retrospectively analyzed from the prospectively collected database of 7 centers participating to the Italian Research Group for Gastric Cancer.Disease-specific and disease-free survival after 3, 5, and 10 years were 90.4%, 86.1%, 75.9%, and 72.1%, 57.3%, 57.3%, respectively. Mortality was 1.7%. The factors associated with a better disease-free survival at univariate analysis were age60, T2 tumors, distal location, intestinal histotype, and number of retrieved nodes25; depth of infiltration and histotype were the only 2 independent predictors of 5-year recurrence-free survival at multivariate analysis.These parameters must be considered to stratify node-negative gastric cancer patients for an adjuvant treatment and follow-up scheduling. Survival was similar to that previously reported by Eastern Centers. Lymphadenectomy is suggested to be effective, and retrieval of more than 25 nodes may be warranted.

The incidence of gastric cancer (GC) is decreasing worldwide, especially for intestinal histotype of the distal third of the stomach. On the contrary, proximal location and diffuse Lauren histotype have been reported to be generally stable over time. In the west, no clear improvement in long-term results was observed in clinical and population-based studies. Results of treatment in these neoplasms are strictly dependent on tumor stage. Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however, results are still unsatisfactory for advanced stages (III and IV), for which additional treatments could provide a survival benefit. This implies a tailored approach to GC. The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC. Perioperative or postoperative treatments, including chemotherapy, chemoradiotherapy, targeted therapies, and hyperthermic intraperitoneal chemotherapy have been reviewed, and the main ongoing and completed trials have been analyzed. An original tailored multimodal approach to non-cardia GC has been also proposed.

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. 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. 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

This study was aimed at evaluating the prognostic significance of the number of metastatic nodes in early gastric cancer (EGC).In this multicenter retrospective study 652 cases of resected EGC were analyzed. We searched for lymph node metastases-associated risk factors and to identify subsets of patients with different prognosis according to the number of involved nodes.Nodal involvement was observed in 14.1%. A significant correlation was found between the presence of node metastases and tumor size (RR 1.34, P = 0.001), submucosal invasion (RR: 3.14, P = 0.007), Lauren diffuse/mixed type (RR: 4.88, P0.001) and Kodama Pen A type (RR: 4.59, P0.001). The 10-year survival rate was 92% for N0 cases, 82% and 73% for tumors with one to three and four to six positive nodes while it dropped to 27% with more than six metastatic nodes. Interestingly enough, the 10-year risk of recurrence diminished with the increasing number of retrieved nodes (15) even in N0 patients.Nodal involvement confirmed to be a significant prognostic factor. In view of the trend to a lower risk of recurrence when more than 15 nodes were retrieved and the better staging achieved we consider D2 lymphadenectomy the treatment of choice.

The present study aimed at investigating whether in gastric cancer patients stage migration occurs with extension of lymphadenectomy, when node metastases are staged according to the new pN classification (UICC 1997). The investigation involved 921 patients, who underwent R0 gastric resection for gastric cancer between 1988 and 1998 in three different Italian centres: Verona (n=236), Forli (n=409), Siena (n=276). The relation among lymphadenectomy and pN category was assessed by Kendall's partial rank-order correlation coefficient, controlling for depth of tumour invasion. A direct evaluation of the Will Rogers phenomenon was accomplished in the Verona series, by comparing the number of positive nodes actually observed with the number of positive nodes which would have been retrieved by a less extended lymphadenectomy (D1). The number of positive nodes increased remarkably with the enlargement of lymphadenectomy, especially in pT2 patients (from 2.2±3.9 in D1 to 3.9±5.0 in D3) and in pT3/pT4 patients (from 5.1±5.9 in D1 to 11.3±12.6 in D3). Non-parametric statistics highlighted a weak (Kendall's partial T=0.128) but significant (P

Background: Duodenal stump fistula (DSF) is a severe complication of gastrectomy. Although nonsurgical therapy is preferred, surgery is still mandatory in one third of DSF patients. The aim of this article is to analyze the surgical management of DSF and factors related to its outcome. Methods: We performed a retrospective multicenter study using data from January 1990 to November 2011 in 16 Italian surgery centers. We collected 8,268 elective gastrectomies for malignancies, 7,987 by the laparotomic and 281 by the laparoscopic approach. Two hundred five patients developed a DSF, 75 of whom underwent surgery for DSF. We analyzed mortality and DSF healing time as well as the impact of clinical, oncological, and surgical characteristics. Results: The laparoscopic approach increased the risk of DSF development (odds ratio 5.6, 95% confidence interval 2.7–10.6, P&nbsp

In an attempt to attract a wider diversity of professionals to the 10th International Gastric Cancer Association Congress (IGCC) held in June 2013, the Scientific Committee of the conference organized a number of pre-congress Web Round Tables to discuss cutting-edge topics relating to gastric cancer treatment. Twenty Web Round Tables, each coordinated by a different chairman, were proposed on the IGCC Website 1 year before the congress. Each chairman identified a number of studies related to the theme of his/her Round Table and invited corresponding authors to send an update of their conclusions in light of their subsequent experience, which would then form the basis of discussion of the Web Round Tables. The chairmen posted several questions regarding these updates on the web and opened a forum for a period of 1-2 months. The forum was free and specifically intended for congress participants. Fifty-one (9.9 %) of the 516 authors contacted took part in the initiative. Two hundred fifty participants from 21 countries joined the forum discussion and posted 671 comments. The Web Round Tables were viewed 15,810 times while the forum was open. Overall, the Web Round Tables aroused considerable interest, especially among young professionals working in the area of gastric cancer who had the opportunity to contact and interact with experts in what often turned out to be an interesting and lively exchange of views. All the discussions are now freely available for consultation on the IGCC website. The Web Round Table experience was presented, with great success, during the conference at special afternoon sessions.

The Italian Research Group for Gastric Cancer supports the practice of follow-up after radical surgery for gastric cancer.This multicenter, retrospective study (1998-2009) included patients with T1-4N0-3M0 gastric cancer who had undergone D2 gastrectomy and lymphadenectomy, with at least 15 lymph nodes examined, and who had developed recurrent disease. Timing and site of recurrence were correlated to the actual scheduled follow-up timing and modalities.From eight centers, 814 patients with recurrent cancer and over 1,754 (46.4 %) patients undergoing gastrectomy were investigated (median follow-up 31 months). The most frequent sites of recurrence were local/regional lymph nodes (35.4 %), liver (24.3 %), peritoneum (30.3 %), lung (10.4 %) and intraluminal (7.5 %). Ninety-four percent of the recurrences were diagnosed within 2 years and 98 % within 3 years. Thoracoabdominal computed tomography (CT) scan and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET) detected more than 90 % of recurrences, abdominal ultrasound detected 70 % and tumor markers detected 40 %, while10 % were identified by physical examination, chest X-ray, and upper gastrointestinal endoscopy. Twenty-six percent of patients with recurrence were treated, but only 3.2 % were treated with potentially radical intent.Oncological follow-up after radical surgery for gastric cancer should be focused in the first 3 years, and based mainly on thoracoabdominal CT scan and 18-FDG-PET.

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in 69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1–G2 grading, I and II tumor—node—metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. Clin Cancer Res; 20(6); 1502–12. ©2014 AACR.

BACKGROUND: During the 1970s, a special type of Gastric Cancer with excellent prognosis (early gastric cancer; EGC) was identified by the Japanese Research Society for Gastric Cancer. EGC has been defined as a tumor which invades the mucosa and/or submucosa, regardless of the lymph node status. Using this definition, we identified an initial phase of tumor development which could be treated both endoscopically and surgically.METHODS: We examined 412 EGC patients, recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an end-point of interest for the survival analysis.RESULTS: Submucosal tumors ( P = 0.008), Pen A (see definition below) type disease ( P = 0.0001), and lymph node-positive cancers ( P = 0.0002) were significant prognostic factors on univariate analysis. Moreover, bivariate analysis showed that the worst prognosis, in terms of survival, was for patients with nodal involvment, submucosal invasion, and node-positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a lesion with a diameter of less than 4 cm, which invades the submucosa diffusely. Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa extensively, with nodular masses, causing the complete destruction of the muscularis mucosae.CONCLUSION: In our series, Pen A type was an important prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49-19.86. For this reason, we believe it is important to evaluate the infiltration into the wall in all patients with EGC, paying particular attention to the growth pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a considerably worse prognosis and this finding was reinforced when lymph node metastases coexisted. We suggest, therefore, that surgical treatment with at least a D2 lymphadenectomy is performed in all these patients, as the lesions must be considered to be advanced, no longer being EGC.

e15148 Background: The treatment of these patients is controversial and influenced by personal, often passive, attitude. Knowledge of variables affecting outcome may promote clinical pragmatism.We surveyed the clinical approach to the subset of patients presenting with synchronous hepatic metastases as sole metastatic site at diagnosis of gastric cancer, focusing on the results achieved by different treatments and investigated the prognostic factors of major clinical relevance. Methods: Retrospective multi-centre chart review evaluating 210 patients admitted in surgical units. We studied how survival from surgery or diagnosis was influenced by different patient-related, gastric cancer-related, metastases-related and treatment-related candidate prognostic factors. Results: Seventeen patients received supportive care, 44 minor palliative surgery, 98 palliative gastrectomy in 16 cases associated to R+ hepatectomy, while 51 patients received both curative gastrectomy and hepatic resection/s (R0). Adjuvant chemotherapy was administered to 41 patients. Therapeutic approach was selected on the basis of stage of disease, patients’ general conditions and surgeon’s attitude toward the disease, without any pre-set common criteria, in absence of institutional protocols or guidelines. Surgical mortality was 4.6%, surgical morbidity 17.6%. Survival was independently influenced by the degree of hepatic involvement (p= 0.036) but therapeutic approach to the metastases was the principal prognostic variable (p

Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.