Genomic events stratifying prognosis of early gastric cancer.

BACKGROUND: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. METHODS: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. RESULTS: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). CONCLUSIONS: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.

International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

Textbook Oncological Outcome in European GASTRODATA.

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM).

OBJECTIVES: Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. METHODS: Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). RESULTS: In the final round, 23 out of 24 items obtained agreement ( ≥ 8) and consensus ( ≤ 2) and 19 out 24 items obtained a good stability (p > 0.05). CONCLUSIONS: The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making. KEY POINTS: • Imaging represents the cornerstone for tailored treatment in GC patients. • CT-structured radiology report in GC patients is useful for multidisciplinary decision making.

Early Gastric Cancer: identification of molecular markers able to distinguish submucosa-penetrating lesions with different prognosis.

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.

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

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

Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study.

OBJECTIVE: Utilizing a standardized dataset based on a newly developed list of 27 univocally defined complications, this study analyzed data to assess the incidence and grading of complications and evaluate outcomes associated with gastrectomy for cancer in Europe. SUMMARY BACKGROUND DATA: The absence of a standardized system for recording gastrectomy-associated complications makes it difficult to compare results from different hospitals and countries. METHODS: Using a secure online platform (www.gastrodata.org), referral centers for gastric cancer in 11 European countries belonging to the Gastrectomy Complications Consensus Group recorded clinical, oncological, and surgical data, and outcome measures at hospital discharge and at 30 and 90 days postoperatively. This retrospective observational study included all consecutive resections over a 2-year period. RESULTS: A total of 1349 gastrectomies performed between January 2017 and December 2018 were entered into the database. Neoadjuvant chemotherapy was administered to 577 patients (42.8%). Total (46.1%) and subtotal (46.4%) gastrectomy were the predominant resections. D2 or D2+ lymphadenectomy was performed in almost 80% of operations. The overall complications' incidence was 29.8%; 402 patients developed 625 complications, with the most frequent being nonsurgical infections (23%), anastomotic leak (9.8%), other postoperative abnormal fluid from drainage and/or abdominal collections (9.3%), pleural effusion (8.3%), postoperative bleeding (5.6%), and other major complications requiring invasive treatment (5.6%). The median Clavien-Dindo score and Comprehensive Complications Index were IIIa and 26.2, respectively. In-hospital, 30-day, and 90-day mortality were 3.2%, 3.6%, and 4.5%, respectively. CONCLUSIONS: The use of a standardized platform to collect European data on perioperative complications revealed that gastrectomy for gastric cancer is still associated with heavy morbidity and mortality. Actions are needed to limit the incidence of, and to effectively treat, the most frequent and most lethal complications.

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

BACKGROUND: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. METHODS: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. RESULTS: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72-11.3, 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.

International consensus on a complications list after gastrectomy for cancer.

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.

E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer.

CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miRs) are involved in its transcriptional control. We evaluated CDH1 expression by quantitative real-time PCR (RT-qPCR) in 33 IGC patients and found a significant downregulation in tumor tissues compared to normal counterparts (p-value = 0.025). Moreover, 14 miRs, predicted to be involved in CDH1 regulation in both a direct and indirect manner, were selected and analyzed by RT-qPCR in an independent case series of 17 IGCs and matched normal tissues. miR-101, miR-26b, and miR-200c emerged as significantly downregulated and were confirmed in the case series of 33 patients (p-value < 0.001). Finally, we evaluated EZH2 expression, a target of both miR-101 and miR-26b, which showed significant upregulation in IGCs (p-value = 0.005). A significant inverse correlation was observed between EZH2 overexpression and CDH1, miR-101, and miR-26b levels (p-value < 0.001). Our results reinforce the link between CDH1 and IGC, highlighting the role of miRs in its transcriptional control and improving our understanding of GC subtypes and biomarkers.

Early Gastric Cancer: Clinical Behavior and Treatment Options. Results of an Italian Multicenter Study on Behalf of the Italian Gastric Cancer Research Group (GIRCG).

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.

Laparoendoscopic rendezvous in the treatment of cholecysto-choledocholitiasis: a single series of 200 patients.

BACKGROUND AND AIM: Although the ideal management of cholecysto-choledocholitiasis is controversial, the two-stage approach, namely the common bile duct (CBD) clearance through endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy, remains the standard way of management. However, whenever feasible, the one-stage approach, using the so-called "laparoendoscopic rendezvous" (LERV) technique, offers some advantages, mainly reducing the hospital stay and the risk of post-ERCP pancreatitis. The aim of this study was to evaluate the safety and the efficacy of the one-stage approach, and to compare our results with data from available large studies. MATERIALS AND METHODS: We reviewed our series of consecutive patients with cholecysto-choledocholitiasis treated by LERV from January 2003, to October 2016. Both elective and emergency cases were included. The primary end-point was the efficacy to obtain the CBD stones clearance. Secondary end-points were morbidity and mortality, operative time, conversion rate, and in-hospital stay. RESULTS: A total of 200 patients underwent a LERV procedure for the intra-operative diagnosis by intra-operative cholangiogram of cholecysto-choledocholitiasis. In 187 patients (93.5%), it was possible to cannulate the cystic duct with the jag-wire. Success rate was 95%. Conversion rate was 3%. The mean operative time was 135 min and the mean in-hospital stay was 4 days. 29 (14.5%) were the early complications, six mild pancreatitis. Four patients required re-operation during the hospital stay. 11 patients (5.5%) developed late complications during a median follow-up of 57.7 months. CONCLUSIONS: Our results confirm that LERV technique is a safe procedure with high success rates for the treatment of cholecysto-choledocholitiasis. The major advantages include the single-stage treatment, the shorter hospital stay, and the lower incidence of post-ERCP pancreatitis.

Incidence and Prognostic Value of Metastases to "Posterior" and Para-aortic Lymph Nodes in Resectable Gastric Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015.

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.

Surgical management of duodenal stump fistula after elective gastrectomy for malignancy: an Italian retrospective multicenter study.

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 < 0.001). The indication for first DSF surgery was intra-abdominal sepsis; the failure rate was over 30%, associated with the appearance of fistulas of neighboring organs, bleeding, and the need for reoperations. The mortality rate was 28% and was related to the presence of vascular disease (P = 0.04), more than one reoperation (P = 0.05), sepsis (P < 0.001), and renal failure (P < 0.001). Fifty-four patients recovered after a median of 39 days (interquartile range 22-68 days); the need to perform more reoperations (P < 0.01) and the presence of an abdominal abscess (P < 0.01) led to an increase in healing time. CONCLUSIONS: Surgery for DSF has a poor prognosis. Our data will help to identify patients at risk of death, but unfortunately could not establish the best surgical procedure applicable to all cases of DSF.

Follow-up after gastrectomy for cancer: the Charter Scaligero Consensus Conference.

PURPOSE: 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. METHODS: 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." RESULTS: 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. CONCLUSION: 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.

Krukenberg Tumors of Gastric Origin: The Rationale of Surgical Resection and Perioperative Treatments in a Multicenter Western Experience.

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.

Gastric cancer and synchronous hepatic metastases: is it possible to recognize candidates to R0 resection?

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.

Is a clear benefit in survival enough to modify patient access to the surgery service? A retrospective analysis in a cohort of gastric cancer patients.

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.