Full Robotic Distal Pancreatectomy: Safety and Feasibility Analysis of a Multicenter Cohort of 236 Patients.

Introduction. Despite the widespread use of the robotic technology, only a few studies with small sample sizes report its application to pancreatic diseases treatment. Our aim is to present the results of a multicenter study on the safety and feasibility of robot-assisted distal pancreatectomy (RDP). Materials and Methods. All RDPs for benign, borderline, and malignant diseases performed in 5 referral centers from 2008 to 2016 were included. Perioperative outcomes were evaluated. Results. Two hundred thirty-six patients were included. Spleen preservation was performed in 114 cases (48.3%). Operative time was 277.8 ± 93.6 minutes. Progressive improvement in operative time was observed over the study period. Conversion rate was 6.3%. Morbidity occurred in 102 cases (43.2%), mainly due to grade A fistulas. Reoperation was required in 10 patients. Postoperatively, 2 patients died of sepsis due to a grade C fistula. Hospital readmission was necessary in 11 cases. A R0 resection was always achieved, with a mean number of 16.2 ± 15 harvested lymph nodes. Conclusion. To our knowledge, this is one of the largest RDP series. Safety and feasibility including the low conversion rate, the high spleen preservation rate, the adequate operative time, and the acceptable morbidity and mortality rates confirm the validity of this technique. Appropriate oncological outcomes have been also obtained.

Short-term and long-term outcomes after robot-assisted versus laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors (pNETs): a multicenter comparative study.

PURPOSE: Minimally invasive surgery has increasingly gained popularity as a treatment of choice for pancreatectomy with encouraging initial results in robotic distal pancreatectomy (RDP). However, few data are available on the comparison between RDP and laparoscopic distal pancreatectomy (LDP) for pancreatic neuroendocrine tumors (pNETs). Our aim, thus, is to compare perioperative and long-term outcomes as well as total costs of RDP and LDP for pNETs. METHODS: All RDPs and LDPs for pNETs performed in four referral centers from 2008 to 2016 were included. Perioperative outcomes, histopathological results, overall (OS) and disease-free survival (DFS), and total costs were evaluated. RESULTS: Ninety-six RDPs and 85 LDPs were included. Demographic and clinical characteristics were comparable between the two cohorts. Operative time was 36.5 min longer in the RDP group (p = 0.009) but comparable to LDP after removing the docking time (247.9 vs 233.7 min; p = 0.6). LDP related to a lower spleen preservation rate (44.7% vs 65.3%; p < 0.0001) and higher blood loss (239.7 ± 112 vs 162.5 ± 98 cc; p < 0.0001). Advantages in operative time for RDP were documented in case of the spleen preservation procedures (265 ± 41.52 vs 291 ± 23 min; p = 0.04). Conversion rate, postoperative morbidity, and pancreatic fistula rate were similar between the two groups, as well as histopathological data, OS, and DFS. Significant advantages were evidenced for LDP regarding mean total costs (9235 (± 1935) € vs 11,226 (± 2365) €; p < 0.0001). CONCLUSIONS: Both RDP and LDP are safe and efficacious for pNETs treatment. However, RDP offers advantages with a higher spleen preservation rate and lower blood loss. Costs still remain the main limitation of the robotic approach.

The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer.

BACKGROUND AND PURPOSE: Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. PRIMARY OBJECTIVE: pathological outcome (TRG 1-2) among arms. MATERIALS AND METHODS: Low-located cT2N0-2M0, cT3N0-2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, +10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7-9 weeks after radiochemotherapy. RESULTS: From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G ≥ 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up:5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155). CONCLUSION: Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions.

Billroth II reconstruction in gastric cancer surgery: A good option for Western patients.

PURPOSE: The aim of this study is to report the short and long-term results of a cohort of patients who underwent Billroth II (BII) Distal Gastrectomy (DG) for gastric cancer (GC), in a tertiary referral Western center. METHODS: From January 2005 to December 2015, a prospective observational study was conducted in candidate patients to elective gastrectomy for cancer. RESULTS: Among 514 patients observed with GC, a series of 258 patients underwent BII DG for middle/lower third GC. Postoperative mortality and complication rates were 1.5% and 12.4% respectively. The overall and disease-free 5-year survival rates were 78% and 69%, respectively. Young age, lymph nodes retrieved, radicality of resection, and early tumor stages were independent positive prognostic factors at multivariate analysis for 5-year overall survival. Abdominal complications and advanced tumor stages negatively influenced 5-year disease-free survival at multivariate analysis. CONCLUSION: BII provides excellent results in terms of short and long-term prognosis and should be regarded as an acceptable reconstructive option following DG for GC.

Total vs proximal gastrectomy for adenocarcinoma of the upper third of the stomach: a propensity-score-matched analysis of a multicenter western experience (On behalf of the Italian Research Group for Gastric Cancer-GIRCG).

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.

Classification of nodal stations in gastric cancer.

The lymphatic drainage from the stomach is anatomically elaborate and it is very hard to predict the pattern of lymph node (LN) metastases from gastric cancer (GC). However, there are LN stations metastases that are more frequently observed depending on the tumor location. Furthermore, the incidence of metastasis to various regional LN stations depends on the depth of gastric-wall invasion. The Japanese Gastric Cancer Association (JGCA) classifies the regional LNs draining the stomach into 33 regional lymphatic stations. These are distinguished into three (N1-N3) groups with respect to the location of the primary tumor. The aim of this classification is to provide a common language for the clinical, surgical, and pathological description of GC.

Postoperative hyperglycemia in nondiabetic patients after gastric surgery for cancer: perioperative outcomes.

BACKGROUND: Hyperglycemia (HG) is widely known to be associated with increased postoperative complications after colorectal surgery. Very few data on the effects of HG on patients after gastric surgery for cancer are reported in literature. The aim of this study was to evaluate the effects of postoperative HG in non-diabetic patients undergoing gastrectomy for cancer. METHODS: One hundred and ninety-three consecutive gastrectomies for cancer performed between January 2010 and December 2015 were considered. Diabetic patients, and those undergoing pancreatic resections were excluded. Postoperative blood glucose levels were monitored in the first 72 h after surgery. Postoperative complications, mortality, and postoperative course were analyzed in patients who experienced postoperative HG (blood glucose level; BGL > 125 mg/dl) compared with euglycemic patients (BGL ≤ 125 mg/dl). Differences between mild HG (BGL between 125 and 200 mg/dl) and severe HG (BGL ≥ 200 mg/dl) were also analyzed. RESULTS: Ninety-six patients (55.5 %) experienced postoperative HG. In 11 patients (6.4 %), a severe postoperative HG was found. Postoperative BGL > 200 mg/dl was related to worse outcomes than those experienced by euglycemic patients (and even than patients who experienced mild postoperative HG). The postoperative complications rate was 24.8 % (43 patients out of 173), but significantly higher in patients with postoperative severe HG compared to mild HG and normoglycemic patients (63.6, 30.6, and 13 %, respectively, p < 0.001). CONCLUSION: Poor postoperative glycemic control seems to be related to worse postoperative outcomes even in patients undergoing elective gastric surgery for cancer.

Altered mitochondrial quality control signaling in muscle of old gastric cancer patients with cachexia.

Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions.

Indications and results of pancreatic stump duct occlusion after duodenopancreatectomy.

Severe post-operative complications after pancreaticoduodenectomy (PD) are largely due to pancreatic fistula onset. The occlusion of the main pancreatic duct using synthetic glue may prevent these complications. Aim of this study is to describe this technique and to report short- and long-term results as well as the post-operative endocrine and exocrine insufficiency. Two hundred and four patients who underwent PD with occlusion of the main pancreatic duct in a period of 15 years were retrospectively analyzed. Post-operative complications and their management were the main aim of the study with particular focus on pancreatic fistula incidence and its treatment. At 1-year follow-up endocrine and exocrine functions were analyzed. We observed a 54 % pancreatic fistula incidence, most of which (77/204 patients) were a grade A fistula with little change in medical management. Twenty-eight patients developed a grade B fistula while only 2 % of patients (5/204) developed a grade C fistula. Nine patients required re-operation, 5 of whom had a post-operative grade C fistula. Post-operative mortality was 3.4 %. At 1-year follow-up, 31 % of patients developed a post-operative diabetes while exocrine insufficiency was encountered in 88 % of patients. The occlusion of the main pancreatic duct after PD can be considered a relatively safe and easy-to-perform procedure. It should be reserved to selected patients, especially in case of soft pancreatic texture and small pancreatic duct and in elderly patients with comorbidities, in whom pancreatic fistula-related complications could be life threatening.

Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness.

Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy.

A case report of a giant rectal adenoma causing secretory diarrhea and acute renal failure: McKittrick-Wheelock syndrome.

BACKGROUND: The McKittrick-Wheelock syndrome is a rare depletion syndrome caused by a secretory villous adenoma or a carcinoma of the rectosigmoid tract. An aggressive hydroelectrolyte rebalancing is often needed, and curative treatment is obtained only with complete removal of the lesion, by endoscopy or surgery. Low clinical suspicion often delays the diagnosis, resulting in detrimental complications. CASE PRESENTATION: We report the case of a 75-year-old woman, presenting to the emergency department with acute renal failure and electrolyte imbalance, reporting an history of recurrent episodes of dehydration and chronic diarrhea. After being admitted to the nephrology department she underwent diagnostic investigation that revealed the presence of a giant adenoma of the rectum. The patients received supportive therapy and was subsequently treated with surgery, with a favorable outcome. CONCLUSIONS: A prompt diagnosis plays an important role in the treatment of McKittrick-Wheelock syndrome. We describe a case of this condition in detail and review the related literature, underlining the typical diagnostic features and exploring the possible therapeutic options.

Surgical Management of Retroperitoneal Soft Tissue Sarcomas: Role of Curative Resection.

Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. However, factors affecting the recurrence and long-term survival are not well understood. The aim of this study was to assess clinical, pathological, and treatment-related factors affecting prognosis in patients with retroperitoneal sarcomas. The hospital records of 107 patients who underwent surgical exploration at our unit for primary or recurrent retroperitoneal sarcomas between 1984 and 2013 were reviewed. Of these patients, 92 had a primary tumor and 15 had a recurrent neoplasm. Study end points included factors affecting overall and recurrence-free survival for the 92 patients with primary disease. Mean follow-up was 79.7 ± 56.3 months. Only the patients undergoing surgery for primary sarcoma were included in this study. Overall 5-year survival was 71 per cent. Disease-free 5-year survival was 65 per cent. Only tumor grade affects overall and disease-free survival. This study confirmed the importance of an aggressive surgical management for retroperitoneal sarcomas to offer these patients the best chance of cure. In our series, only the tumor grade seems to be associated with worse outcome and higher rate of recurrence, regardless of the size of the tumor.

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.

Anastomotic leakage after anterior resection for rectal cancer with mesorectal excision: incidence, risk factors, and management.

We investigated risk factors and prognostic implications of symptomatic anastomotic leakage after anterior resection for rectal cancer, and the influence of a diverting stoma. Our retrospective review of prospective collected data analyzed 475 patients who underwent anterior resection for rectal cancer. Uni- and multivariate analysis was made between anastomotic leakage and patient, tumor, and treatment variables, either for the overall group (n = 475) and in the midlow rectal cancer subgroup (n = 291). Overall rate of symptomatic leakage was 9 per cent (43 of 475) with no related postoperative mortality. At univariate analysis, significant factors for leak were a tumor less than 6 cm from the anal verge (13.7 vs 6.6%; P = 0.011) and intraoperative transfusions (16.9 vs 4.3%; P = 0.001). Similar results were observed in the midlow rectal cancer subgroup. At multivariate analysis, no parameter resulted in being an independent prognostic factor for risk of leakage. In patients with a leakage, a temporary enterostomy considerably reduced the need for reoperation (12.5 vs 77.8%; P < 0.0001) and the risk of a permanent stoma (18.7 vs 28.5%; P = 0.49). The incidence of anastomotic failure increases for lower tumors, whereas it is not influenced by radiotherapy. Defunctioning enterostomy does not influence the leak rate, but it mitigates clinical consequences.

Trends in clinical features, postoperative outcomes, and long-term survival for gastric cancer: a Western experience with 1,278 patients over 30 years.

BACKGROUND: The aim of the present study was to identify temporal trends in long-term survival and postoperative outcomes and to analyze prognostic factors influencing the prognosis of patients with gastric cancer (GC) treated in a 30-year interval in a tertiary referral Western institution. METHODS: Between January 1980 and December 2010, 1,278 patients who were diagnosed with GC at the Digestive Surgery Department, Catholic University of Rome, Italy, were identified. Among them, 936 patients underwent surgical resection and were included in the analysis. RESULTS: Over time there was a significant improvement in postoperative outcomes. Morbidity and mortality rates decreased to 19.4% and 1.6%, respectively, in the last decade. By contrast, the multivisceral resection rate steadily increased from 12.7% to 29.6%. The overall five-year survival rate steadily increased over time, reaching 51% in the last decade, and 64.5% for R0 resections. Multivariate analysis showed a higher probability of overall survival for early stages (I and II), extended lymphadenectomy, and R0 resections. CONCLUSIONS: Over three decades there was a significant improvement in perioperative and postoperative care and a steady increase in overall survival.

Gastric stump cancer after distal gastrectomy for benign disease: clinicopathological features and surgical outcomes.

PURPOSE: The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease. METHODS: We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6-207) months. RESULTS: One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2-T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002). CONCLUSIONS: Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC.

Naso-gastric or naso-jejunal decompression after partial distal gastrectomy for gastric cancer. Final results of a multicenter prospective randomized trial.

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.

Multivisceral resection for locally advanced gastric cancer: an Italian multicenter observational study.

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.