Search

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

Introduction: We evaluated the gene expression levels of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha in skeletal muscle samples of patients with gastric cancer and controls., Methods: We studied 38 cancer patients and 12 controls who underwent surgery for gastric adenocarcinoma and benign abdominal diseases, respectively. A biopsy specimen was obtained from the rectus abdominis muscle from all participants. The relative gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha was determined by quantitative real-time polymerase chain reaction analysis., Results: Atrogin-1 and MuRF1 mRNA expression was similar between cancer patients and controls and was unaffected by the disease stage or the severity of body weight loss. Transcript levels of myostatin and follistatin did not differ between cases and controls and were similar across disease stages and categories of weight loss. Finally, no differences were detected in activin A and inhibin alpha gene expression between cancer patients and controls., Conclusions: In skeletal muscle, the gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha is not affected by the presence of cancer. The expression of atrophy-related genes is unaffected by the disease stage and the degree of weight loss., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Cholelithiasis is more frequent in patients after gastrectomy, due to dissection of vagal branches and gastrointestinal reconstruction., Methods: A randomized controlled trial was conducted from November 2008 to March 2012. Patients were randomized into two groups: prophylactic cholecystectomy (PC) and standard gastric surgery only (SS) for curable cancers. We planned three end points: evaluation of the number of patients who developed symptoms and needed further surgery for cholelithiasis after standard gastric cancer surgery, evaluation of the incidence of cholelithiasis overall after standard gastric cancer surgery and perioperative complications or costs of prophylactic cholecystectomy. The present study answers to the last end point only., Results: After 40 months from the beginning of study, 172 patients were eligible from 9 Centers. Ten patients refused consent and 32 were excluded due to flawing of inclusion criteria (not confirmed adenocarcinomas and no R0 surgery). Therefore, final analysis included 130 patients: 65 in PC group and 65 in SS. Among PC group, 12 patients had surgical complications during the perioperative period; only 1 biliary leakage, conservatively treated, might have been caused by prophylactic cholecystectomy. 6 patients had surgical complications in SS group. One postoperative death occurred in PC group due to pulmonary embolism. Differences were not statistically significant. Similarly, no differences were significant in duration of surgery, blood loss, hospital stay., Conclusions: Concomitant cholecystectomy during standard surgery for gastric malignancies seemed to add no extra perioperative morbidity, mortality and costs to the sample included in the 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.

Background: The aim of this study was to evaluate the possibility of a different path to achieve curative surgery in patients older than age 70 years and affected by resectable gastric cancer., Study Design: This is a multicentric retrospective study based on an analysis of 1,465 patients with gastric adenocarcinoma who underwent surgery with curative intent. Patients were divided into 2 age groups (younger than 70 years vs older than 70 years) and were evaluated with respect to postoperative morbidity and mortality and survival., Results: Postoperative morbidity and mortality in elderly and nonelderly groups were 24.8% vs 20.6% and 2.6% vs 3.7%, respectively (p = NS). In the elderly group, multivisceral resection was independently associated with surgical complications (hazard ratio [HR] = 1.988; 95% CI, 1.124-3.516; p = 0.018), total gastrectomy with medical complications (HR = 2.007; 95% CI, 1.165-3.459; p = 0.012), and higher postoperative mortality (HR = 4.319; 95% CI, 1.571-11.873; p = 0.005); D1 lymph node dissection was predictive of a lower postoperative mortality rate (HR = 0.219; 95% CI, 0.080-0.603; p = 0.003). Five-year overall survival rates differed significantly in young and elderly patients (58.9% vs 38.9%; p < 0.001), and 5-year cancer-specific survival did not show any significant difference., Conclusions: Age should not be considered as a factor in the selection of treatment for gastric cancer patients. Curative surgery can be performed as safely in elderly patients as in younger patients, with comparable postoperative results and long-term survival rates, although the life expectancy of elderly patients is shorter., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: For more than a century the extent of surgical treatment of gastric cancer is a matter of debate. Through experience, evaluation and research, the outcome of gastric cancer has improved. Many aspects are of influence of outcome, but only a radical resection can offer long-term outcomes. In this review, we will discuss the history and current status of the extent of lymph node dissection., Materials and Methods: Some issues about the extent of gastric resection seem to have been settled. For survival it is not necessary to perform a total gastrectomy if free resection margins can be obtained with a subtotal gastrectomy. In the context of postoperative morbidity and mortality a subtotal gastrectomy is to be preferred. Microscopic resection line involvement has shown to be of great influence on prognosis., Discussion: At this moment the main discussion centres around the extent of lymph node dissection, locoregional recurrence and to the influence of additional treatment. For many years it has been debated whether an extended lymph node dissection for gastric cancer is beneficial. Theoretically, removal of a wider range of lymph nodes by extended lymph node dissection increases the chances for cure. Such resection, however, may be irrelevant if there are no lymph nodes affected or if the cancer has developed into a systemic disease, or if it increases morbidity and mortality substantially., Conclusion: Relapse after curative surgery because of local recurrence or regional lymph node metastasis have been shown in up to 87.5% of patients. The extent of surgery, however, may be of influence on the locoregional recurrence rate.

Background: This study was to assess the influence of perioperative blood transfusions on the prognosis of patients undergoing a potentially curative resection for gastric cancer and to investigate the interaction between transfusions and splenectomy., Materials and Methods: Between January 1990 and December 2005, 927 patients from 6 Italian tertiary referral centers underwent curative resections for gastric cancer. Clinical and pathologic variables were prospectively collected. The influence of perioperative blood transfusions on survival were evaluated by univariate and multivariate analysis. Moreover, the influence of splenectomy both in transfused and nontransfused patients undergoing total gastrectomy was also evaluated., Results: The overall 5-year survival was 54.6%. The 5-year survival rate in transfused patients (n = 327) was 50.6% compared with 56.6% in nontransfused patients (n = 600) (P = .094). In the subgroup of patients who underwent total gastrectomy with spleen preservation (n = 209), 5-year survival rate was 46% and 51.4% in transfused and nontransfused patients, respectively (P = .418); those who underwent total gastrectomy with splenectomy (n = 199) presented a 5-year survival rate of 45% in transfused group compared with 39.1% in nontransfused patients (P = .571)., Conclusions: Our study indicates a slightly, but not significantly, negative effect of allogeneic blood transfusion on prognosis of gastric cancer patients. In the subgroup of patients who underwent total gastrectomy, splenectomy seems to invert this mild effect, with a positive influence on overall survival.

The influence of cancer on skeletal muscle calpain expression and activity in humans is poorly understood. We tested the hypothesis that calpain activity is increased in skeletal muscle from gastric cancer patients with no or <5% weight loss. Muscle biopsies were obtained from rectus abdominis muscle in 15 patients who underwent surgery for gastric cancer and had <5% weight loss and also in 15 control patients. Calpain activity was determined using a calpain-specific substrate in the absence or presence of calcium. The expression of μ- and m-calpain, calpastatin, atrogin-1, and MuRF1 was determined by real-time polymerase chain reaction. Calpain activity was increased by 70% in cancer patients compared with controls. There were no differences in mRNA levels for μ- and m-calpain, calpastatin, atrogin-1, or MuRF1 between control and cancer patients. Calpain activity may be increased in muscle from gastric cancer patients even before changes in molecular markers of muscle wasting and significant weight loss occur., (Copyright © 2010 Wiley Periodicals, Inc.)

Experimental studies have suggested that defective skeletal muscle regeneration could contribute to muscle wasting in cancer patients. However, data in humans are still lacking. In this study we aimed to assess the expression of the genes involved in muscle regeneration in gastric cancer patients. The RNA expression of the genes involved in muscle regeneration was assessed in the rectus abdominis muscle of patients with gastric cancer (n=30) and in age-matched control subjects (n=8). The Pax7 expression was significantly increased in the muscle of gastric cancer patients, either in the first stages of the disease or in stages IIIA and B. The increased expression was present both in stages IA and B and in stages II and III. The MyoD espression was also higher in the cancer patients than in the controls. However, the increased MyoD expression was present only in stages IA and B and not in the more advanced stages of the disease. The Myf5 expression, as well as that of the neonatal isoform of Myosin Heavy Chain (nMHC) did not differ significantly between the cancer patients and the controls. The necdin expression was negligible in healthy adult muscles and was significantly up-regulated in the muscle of gastric cancer patients. Its expression was highly increased in stages IA and B while it was similar to the control in stages II and III. The results of the present study show that in the skeletal muscle of gastric cancer patients, the expression of the genes involved in muscle regeneration is increased with respect to the controls.

The mechanisms eliciting cancer cachexia are not well understood. Wasting of skeletal muscle is problematic because it is responsible for the clinical deterioration in cancer patients and for the ability to tolerate cancer treatment. Studies done on animals suggest that nuclear factor of kappa B (NF-kappaB) signalling is important in the progression of muscle wasting due to several types of tumours. However, there are no published studies in humans on the role of NF-kappaB in cancer cachexia. In this project, we studied the rectus abdominis muscle in patients with gastric tumours (n=14) and in age-matched control subjects (n=10) for markers of NF-kappaB activation. Nuclear levels of p65, p50 and Bcl-3 were the same in both groups of subjects. However, phospho-p65 was elevated by 25% in the muscles of cancer patients. In addition, expression of the inhibitor of kappa B alpha (IkappaBalpha) was decreased by 25% in cancer patients. Decreased expression of IkappaBalpha reflects its degradation by one of the IkappaBalpha kinases and is a marker of NF-kappaB activation. Interestingly, there was no correlation between the stage of cancer and the extent of IkappaBalpha decrease, nor was there a correlation between the degree of cachexia and decreased IkappaBalpha levels. This suggests that the activation of NF-kappaB is an early and sustained event in gastric cancer. The work implicates the NF-kappaB signalling in the initiation and progression of cancer cachexia in humans and demonstrates the need for additional study of this pathway; it also recommends NF-kappaB signalling as a therapeutic target for the amelioration of cachexia as has been suggested from studies done on rodents.

Hypothesis: Although total gastrectomy (TG) has been generally accepted as the treatment of choice for upper and middle gastric cancers, some issues are still debated. The objective of this retrospective study was to analyze short- and long-term results of TG (radical and palliative) in a series of 400 patients consecutively admitted to our surgical unit., Design: Retrospective cohort study., Setting: Primary and referral hospital care., Patients: Hospital records of 400 patients who consecutively underwent TG between January 1981 and June 2005 were reviewed., Main Outcome Measures: Surgical complications and survival., Results: Three hundred twelve patients underwent radical procedures, and 88 patients underwent palliative procedures. The incidence of postoperative complications was higher among patients who underwent palliative TG (33 of 88 [37.5%]) compared with patients who underwent curative TG (75 of 312 [24.0%]) (P =.01). Mortality was higher among patients who underwent palliative TG (6 of 88 [6.8%]) compared with patients who underwent curative TG (11 of 312 [3.5%]) (P =.18). Five-year survival was 61.8% after curative TG and 12.8% after palliative TG. Ten-year survival was 47.3% after curative TG and 0.0% after palliative TG., Conclusions: This study among 400 consecutive patients who underwent TG at the same surgical unit shows that this surgical procedure in experienced hands can lead to excellent short- and long-term results.

Objective & Aims: The present study aimed at retrospectively evaluating the incidence of mortality and major and minor postoperative complications in patients who underwent surgery for gastric cancer between 2000 and 2006 stratified according to the preoperative percentage weight loss, serum albumin levels and body mass index (BMI)., Methods: One hundred and ninety-six patients affected by gastric cancer admitted to the Division of Digestive Surgery of the Catholic University of Rome between January 2000 and December 2006 were considered eligible and were included in the study. According to the weight loss, patients were divided into three groups: (1) 0-5%; (2) 5.1-10%; (3) >10%. On the basis of serum albumin levels, were divided into three groups: (1) <3.0 g/dl; (2) 3.0-3.4 g/dl; (3) >3.5 g/dl. According to BMI, were divided into four groups: (1) <18.5 kg/m(2); (2) 18.5-24.9 kg/m(2); (3) 25.0-29.9 kg/m(2); (4) >30.0 kg/m(2). Postoperative complications and mortality were reported. Complications were classified by objective criteria as major or minor, and as infectious or non-infectious., Results: The postoperative mortality was 0%. Major infectious complications occurred in 20 patients (10.2%), major non-infectious in 18 (9.2%), minor infectious in 21 (10.7%), whereas minor non-infectious complications were absent. The rate of major infectious, major non-infectious and minor infectious postoperative complications was similar in patients with absent or light weight loss (8.8%, 8.8%, 10.6%, respectively), mild weight loss (15.3%, 11.5%, 9.6%, respectively), or severe weight loss (6.4%, 6.4%, 12.9%, respectively). Similarly, the rate of postoperative complications did not differ between patients with serum albumin <3.0 g/dl (10.8%, 8.1%, 8.1%, respectively); between 3.0 and 3.4 (8.8%, 13.3%, 17.7%, respectively) or > or =3.5 g/dl (10.5%, 7.9%, 8,7%, respectively). According to BMI, the rate of postoperative complications was: 11.7%, 5.8%, and 5.8% for BMI <18.5 kg/m(2); 9.4%, 8.2%, and 11.7% for BMI between 18.5 and 24.9 kg/m(2); 10.7%, 10.7%, and 9.2% for BMI between 25 and 29.9 kg/m(2); 10.3%, 10.3% and 13.7% for BMI >30 kg/m(2). Then, we evaluated the postoperative morbidity only in patients who underwent total gastrectomy or distal subtotal gastrectomy associated with extended lymphadenectomy. In this group of patients, the rate of postoperative complications was comparable in patients with 0-5% (8.8%, 7.7%, 10%, respectively), 5.1-10% (14.6%, 9.7%, 9.7%, respectively), and >10% (7.1%, 7.1%, 14.3%, respectively) weight loss. Also stratifying the patients according to the serum albumin levels, the rate of postoperative complications did not differ significantly (serum albumin <3.0 g/dl: 14.8%, 11.1%, 14.8%, respectively; serum albumin between 3.0 and 3.4 g/dl: 6.2%, 12.5%, 15.6%, respectively; serum albumin > or =3.5 g/dl: 10.4%, 5.8%, 7.0%, respectively). According to BMI, the rate of postoperative complications was: 7.6%, 0%, and 7.6% for BMI <18.5 kg/m(2); 9.5%, 9.5%, and 11.1% for BMI between 18.5 and 24.9 kg/m(2); 12.5%, 8.3%, and 10.4% for BMI between 25 and 29.9 kg/m(2); 9.5%, 9.5% and 9.5% for BMI >30 kg/m(2)., Conclusion: The present study suggests that weight loss and hypoalbuminemia are not associated with an increased risk of mortality and morbidity in patients who underwent surgery for gastric cancer. This study may represent a stimulus for further studies aiming at evaluating the actual role of malnutrition in the development of postoperative complications in major abdominal surgery.

Background: The present study evaluated the effects of preoperative parenteral nutrition (PN) on tumor cell proliferation in malnourished gastric cancer patients., Methods: Twenty malnourished patients affected by gastric cancer were randomized to receive the standard hospital oral diet (control group) or the standard hospital oral diet plus PN (PN group; 0.2 g/kg/d of nitrogen and 30 nonprotein kcal/kg/d). Samples of tumor tissue and surrounding health mucosa were taken by endoscopic biopsies and from the operative specimen, immediately after resection. Tissues were sent for histologic examination and prepared for flow cytometry and for the measurement of the uptake of bromodeoxyuridine (BduR) by cells after in vitro exposure to the agent. The BduR uptake is largely used to assess the proportion of cells actively synthesizing DNA and is one of the principle methods used to measure tumor proliferation., Results: In the PN group, the mean percentage of tumor cells incorporating BduR was 2.51% +/- 1.7% in the endoscopic samples and 1.52% +/- 0.8% in the operative specimens (p = .2). In the normal mucosa, the mean percentage of cells incorporating BduR was 2.24% +/- 1.8% and 1.13% +/- 1.1%, respectively (p = .1). In the control group, the percentage of cells incorporating BduR in the normal mucosa was 1.26% +/- 1.1% at endoscopy and 0.41% +/- 0.3% at surgery (p = .2), whereas the percentage of cells incorporating BduR in the tumor tissue was 1.41% +/- 1.2% at endoscopy and 0.48% +/- 0.6% at surgery (p = .2). The percentage of S-phase cells documented by flow cytometry in the PN group was: in the tumor, 6.6% +/- 2.9% in the endoscopic samples and 5.7% +/- 2.5% in the operative specimens (p = .6); in the normal mucosa, 5.8% +/- 2.5% at endoscopy and 5.4% +/- 0.9% at surgery (p = .7). In the control group, the percentage of proliferating cells measured by flow cytometry was 4.9% +/- 3.2% in the normal mucosa taken by endoscopic biopsy and 5.3% +/- 1.4% in the normal mucosa taken from the operative specimens (p = .8), whereas it was 11.4% +/- 7.2% in the tumor taken with endoscopic biopsy and 9.7% +/- 4% in the tumor tissue taken from the surgical specimens (p = .7)., Conclusions: The present study suggests that PN does not stimulate tumor proliferation in malnourished patients affected by gastric cancer.

Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking. The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A biopsy specimen was obtained from the rectus abdominis muscle. The occurrence of apoptosis in muscle biopsies was determined morphologically by the fluorescent transferase-mediated dUTP nick end labeling assay and by immunohistochemistry for caspase-3 and caspase-1. Mean weight loss was 6+/-2% in cancer patients and 0.5+/-0.1% in controls (p<0.0001). Serum albumin levels (g/dL) were 3.7+/-0.3 in cancer patients and 4.1+/-0.2 in controls (p<0.05). The percentage of apoptotic myonuclei was similar in cancer patients and in controls (1.5+/-0.3 versus 1.4+/-0.2, respectively; p=ns), in gastric cancer patients with mild (1.6+/-0.4) or moderate-severe weight loss (1.4+/-0.5) (p=ns), and in the different stages of disease (stages I-II: 1.5+/-0.7; stage III: 1.3+/-0.4; stage IV: 1.6+/-0.3; p=ns). By immunohistochemistry, caspase-1 and caspase-3 positive fibers were absent in controls and in neoplastic patients. Poly-ADP-ribosyl polymerase, a typical caspase-3 substrate whose processing is indicative of caspase-3 activation, was not cleaved in muscle biopsies of cancer patients. These data suggest that skeletal muscle apoptosis is not increased in neoplastic patients with mild-moderate weight loss and argue against the hypotheses that caspase-3 activation might be an essential step of myofibrillar proteolysis in cancer-related muscle wasting.

Gastrointestinal stromal tumours are a relatively new nosological entity with an increasing incidence. CD117 positivity at immunohistochemical analysis is mandatory to distinguish them from other mesenchymal tumours. A gastric localisation is observed in more than 70% of cases. In the present paper 11 primary gastrointestinal stromal tumours of the stomach operated during the last decade at our institution were retrospectively reviewed. Hospital files and histological slides of 11 patients with gastrointestinal stromal tumours of the stomach undergoing surgical resection at our institution over the period from 1993 to 2003 were reviewed retrospectively. The variables analysed were: morphological and immuno-histochemical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephone follow-up in all patients. Immunohistochemical analysis for CD11 7 proved positive in all patients. The size of the tumours ranged from 3 to 23 cm: tumour size was > 5 cm and > 10 cm in 8 and 3 patients, respectively. Nodal involvement was detected in one patient and another had liver metastases. Surgical treatment consisted of wedge resection in 3 cases, distal subtotal gastrectomy in 4 and total gastrectomy in 4. In 2 patients surgical excision was extended to other organs. No postoperative mortality or major postoperative complications were observed. Nine patients were still alive at follow-up; 1 patient died as a result of a neoplastic relapse (38 months) and 1 died of other causes (48 months). The median survival was 42 months. Gastrointestinal stromal tumours are characterised by slow growth and therefore clinical signs are delayed. For that reason large tumours are often observed at the time of diagnosis. Surgical resection is the only potential curative treatment; but the risk of recurrence (local or at distance) remains high.

Dehiscence of the Roux-en-Y oesophagojejunostomy after total gastrectomy is an infrequent complication that may lead to severe morbidity and even death when it occurs. A prospective multicentre randomised trial was designed to assess the need for routine nasojejunal decompression after total gastrectomy with Roux-en-Y oesophagojejunostomy in patients with gastric cancer. Two hundred and thirty-seven patients undergoing total gastrectomy for gastric cancer were randomly assigned to placement of a nasojejunal tube (NJT group) or not (no-NJT group). The patients were monitored for postoperative complications, mortality and postoperative course. The rates of anastomotic leaks were similar in both groups (NJT group, 6.9%; no-NJT group 5.8%) as were the rates of major postoperative complications (25.9% and 21.5%, respectively) and the overall postoperative mortality rates (0.9% and 0.8%, respectively). There were no differences between the two groups in mean time +/- SD to passage of flatus (4.6 +/- 1.3 and 4.5 +/- 1.7 days, respectively) and to starting a liquid diet (7.8 +/- 2.6 and 7.7 +/- 1.6 days, respectively), or in mean +/- SD postoperative hospital stay (13.5 +/- 7.3 and 13.9 +/- 10.9 days, respectively), mean postoperative pain and postoperative abdominal distension. The results of this study suggest that routine placement of an NJT after Roux-en-Y oesophagojejunostomy is unnecessary in elective total gastrectomy for gastric cancer.

Background: Hereditary diffuse gastric cancer (HDGC) is a disease mediated by down-regulation of the tumor suppressor E-cadherin (CDH1). This disease is particularly dangerous because of the youth of the patients, and for clinical management, hampered by the submucosal spread of tumor invisible at endoscopy. Two mechanisms of CDH1 down-regulation have been described in HDGC: missense mutations in the CDH1 gene and gene silencing through promoter methylation., Materials and Methods: Seven patients affected by HDGC were enrolled. Tumor tissues were checked for CDH1 expression by immunohistochemistry (IHC). CDH1 DNA sequencing was performed for all its 16 exons from tumor and normal tissues of the same patients to detect somatic and germ-line mutations. Methylation promoter study was performed using specific primers and PCR., Results: IHC analysis confirmed CDH1 down-regulation in all patients. DNA sequencing revealed the presence of six missense mutations in five patients. Four mutations were at the EC-3 domain of CDH1, whereas the other two were found in the cytoplasmic region interacting with catenins. All six mutations were absent in normal tissue, thereby excluding its presence in germ-line cells. Four patients exhibited both DNA missense mutations and gene silencing through promoter methylation. In two patients we did not notice either DNA missense mutations or promoter methylation., Conclusion: CDH1 somatic mutations and promoter methylation synergistically induce CDH1 down-regulation in HDGC patients, whereas germ-line mutations are relatively rare. However, other unknown mechanisms of CDH1 suppression are involved to explain CDH1 down-regulation in HDGC patients without CDH1 mutations and promoter methylation.

Objective: To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients., Summary Background Data: Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer., Methods: Biopsies of the rectus abdominis muscle were obtained intraoperatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed., Results: Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity., Conclusions: These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.

The major determinants of the poor prognosis of the patients with proximal-third gastric cancer (proximal gastric cancer or PGC) when compared with that of patients with more distally located gastric tumors (distal gastric cancer or DGC) rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative mortality for PGC patients. We reviewed hospital records of 707 patients with gastric cancer (187 with PGC and 520 with DGC) observed during the period 1981 through 1996 at the same surgical unit. Demographic and pathological data, type of treatment, and hospital morbidity and mortality rates were recorded. Univariate and multivariate survival analysis was used to calculate the 5-year survival probabilities with respect to the following clinical and pathological variables: age, sex, gross appearance according to Borrmann classification, histological type according to Lauren, stage of the disease, tumor location, and type of treatment. PGC was associated with more advanced tumor stage (P < 0.0001), older age (P = 0.039), and higher necessity of extended surgery (P < 0.0001) when compared with DGC. Hospital mortality was 9.6 and 5 per cent in PGC and DGC patients respectively (P = 0.033). Overall 5-year survival was 17.7 and 36.4 per cent in PGC and DGC patients (P < 0.0001): 35.9 versus 57.6% (P = 0.0001) and 3.7 versus 7.6 per cent (P = 0.03) after radical and palliative surgery respectively. At multivariate survival analysis proximal location was found to be independently associated (P = 0.0007) with poor survival. The multivariate model shows the proximal location as an independent predictor of lesser favorable outcome in gastric cancer. The major determinants of the poor prognosis of PGC with respect to DGC rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative morbidity for PGC patients.

The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is hyperactivated in experimental cancer cachexia. The present study aimed at verifying whether the expression of the muscle Ub mRNA is altered in patients with cancer. Total muscle RNA was extracted using the guanidinium isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was measured by ELISA. Ub mRNA levels (arbitrary units, means +/- SD) were 2,345 +/- 195 in GC and 1,162 +/- 132 in CON (P = 0.0005). Ub mRNA levels directly correlated with disease stage (r = 0.608, P = 0.005), being 1,945 +/- 786 in stages I and II, 2,480 +/- 650 in stage III, and 3,799 +/- 66 in stage IV. Ub mRNA and sTNFR did not correlate with age and nutritional parameters. This study confirms experimental data indicating an overexpression of muscle Ub mRNA in cancer cachexia. Lack of correlation with nutritional status suggests that Ub activation in human cancer is an early feature that precedes any clinical sign of cachexia.

Controversy still surrounds the value of extensive regional lymphnode dissection in the treatment of gastric cancer. The aim of the present paper is to give this topic a contribution through the review of the literature and the analysis of personal results.

The hospital records of 639 patients affected by primary gastric cancer who were consecutively admitted to our unit during the period 1981-1995 were reviewed. Overall 220 underwent total gastrectomy (38 palliative), 12 had resection of the gastric stump, 195 had distal subtotal gastrectomy (55 palliative), 78 had bypass procedures, 72 had explorative laparotomy, and 62 had no operation. Univariate and multivariate analyses were used to evaluate 5-year survival with respect to the main clinical, pathologic, and treatment variables after both curative and palliative treatments. Overall the 5-year survival after curative treatment (320 patients-operative mortality excluded) was 55.5%: 91.1% for stage IA, 71.5% IB, 62.4% II, 37.5% IIIA, 31.5% IIIB. Among patients who underwent palliative treatment 5-year survival was 13.1% after gastric resection (total or distal subtotal), 4.9% after the bypass procedures, 0 after explorative laparotomy, and 0 after no operation. Univariate and multivariate survival analyses showed that variables independently associated with poor survival were advanced stage, upper location and D1 lymphadenectomy after curative treatment, tumor spread to distant sites, and nonresectional surgery after palliative treatment. Multivariate analysis showed that even though survival with gastric cancer depends on predetermined factors, the type of surgery can have a significant effect on prognosis after both curative and palliative treatment.

Background: Pancreas-preserving total gastrectomy for gastric cancer has been proposed to remove lymph nodes along the upper border of the pancreas without performing a distal pancreatic resection. However, the original technique includes the ligation of the splenic artery at its origin and thus carries the risk of pancreatic necrosis., Hypothesis: A technique of pancreas-preserving total gastrectomy that includes ligation of the splenic artery approximately 5 cm distally from the root may reduce the risk of postoperative pancreatic necrosis., Design: Case series., Setting: Both primary and referral hospital care., Patients: Hospital records of 228 consecutive patients who, according to a personal technique, underwent D3 pancreas-preserving total gastrectomy for gastric cancer from 1981 to 1997 were reviewed., Main Outcome Measures: Surgical complications, postoperative deaths, and survival., Results: Hospital morbidity and mortality were 33.3% and 3.9%, respectively. No patients experienced pancreatic necrosis. The 5-year survival rate after curative resection was 53.6%: 96.9% for stage IA, 76.3% for stage IB, 63.0% for stage II, 35.6% for stage IIIA, 27.0% for stage IIIB, and 20.3% for stage IV (N3-positive patients) disease., Conclusion: Results of the present study show the efficacy of this method of radical resection for gastric cancer as demonstrated by the low incidence of postoperative complications and high survival rates.

Few reports of the Western countries have investigated the value of palliative surgery for stomach cancer. The aim of this study was to evaluate the results of palliative surgery in a large series of patients affected by gastric carcinoma, consecutively treated by the same surgical team. The hospital records of 305 patients affected by gastric cancer who did not undergo surgical treatment or who underwent a palliative surgical procedure at our unit between 1981 and 1995 were reviewed. Univariate and multivariate analyses were used to calculate the 5-year survival probabilities with respect to the following variables: demographic data, tumor location and gross appearance, spread of the disease, histological type according to P. Lauren, and type of treatment. Multivariate logistic regression analysis showed that resectional surgery and tumor spread limited to local sites were independently associated with better survival. The study indicates that even though there are host-related factors that govern survival in far-advanced stomach cancer, the type of surgery can have a significant effect on prognosis; resectional surgery should be undertaken whenever possible in such patients.

Background/aims: Few reports from the Western hemisphere have investigated the impact of pathological features and surgical modalities on the prognosis of patients affected by early gastric cancer (EGC). In particular, the extent of lymphadenectomy (limited vs. extended) and the type of gastric resection (subtotal vs. total) remain controversial issues in the management of EGC. The aim of this study was to identify factors influencing prognosis in patients affected by EGC., Methodology: Hospital records and pathological specimens of 72 patients with EGC undergoing resective surgery during the period 1981-1995 were retrospectively reviewed. Patient status was determined by follow-up examination or by telephone contact. Univariate and multivariate analysis was used to calculate the 5-year survival probabilities with respect to the following variables: age (< or = 65, > 65), sex, depth of invasion (mucosal, submucosal) tumor location (upper, middle and lower third), gross appearance (type I, type II and type III), size (< or = 1.5 cm, > 1.5 cm), presence or absence of lymph node metastasis, histological type (intestinal, diffuse), extent of lymphadenectomy (limited or extended), and type of gastrectomy (total or distal subtotal). Survival was the outcome variable studied., Results: Multivariate logistic regression analysis showed that age, nodal involvement and depth of invasion were independently associated with poor survival., Conclusions: Results showed a significant dominance of host- and tumor-related factors over the type of surgical procedure on prognosis of EGC patients.

Background: Immunosuppression associated with homologous blood transfusion was first observed in renal allograft transplantation. Clinical effects of transfusion-induced immunosuppression in surgical patients have been debated in the literature for more than a decade with contradictory results., Objective: To investigate whether homologous blood transfusions significantly affect postoperative septic morbidity and mortality in patients undergoing elective surgery for gastric cancer., Design: Case series., Setting: Hospitalized care., Patients: The hospital records of 209 patients who underwent elective surgery for gastric cancer at the Department of Surgery of the Hospital del Mar, Autonomous University of Barcelona in Spain, and at the Department of Surgery of the Catholic University of Rome in Italy from April 1984 to December 1990 were reviewed, and 179 patients were included in the study., Main Outcome Measures: The following variables were entered into univariate and multivariate analyses to identify factors potentially affecting postoperative septic morbidity: demographic data, weight loss, preoperative serum albumin level and lymphocyte count, type and duration of operative procedure, amount and timing of blood transfusion, and stage of disease., Results: Univariate analysis showed that a large quantity of blood transfused (> 1500 mL) and transfusion in the postoperative period (group C) were associated with a worse clinical outcome. Postoperative transfusion was an independent predictor of septic morbidity in multivariate analysis., Conclusions: Despite transfusion-induced immunomodulation, homologous blood transfusion should not be considered a risk factor for postoperative septic morbidity in patients undergoing elective major abdominal surgery. The timing-response relationship between transfusions and septic morbidity in multivariate analysis may be the effect of uncontrolled confounders such as variation of volemia induced by stress response in patients who were developing or had just developed infectious complications.

The review of the literature shows the improvement of outcome of patients with gastric cancer after resection and extended lymphadenectomy. Lymphadenectomy D2/D3 was performed in 206 out of 639 patients with gastric cancer: 5-year survival was 66.3% versus 41.5% of the 121 patients that underwent D1 resection (p < 0.0001). Univariate and multivariate analyses show that proximal location of the cancer, advanced stage and lymphadenectomy limited to perigastric stations are negative prognostic factors. Although there are still different opinions regarding D2 or D3 lymphadenectomies for the operative risks, pancreatic resection (preferring pancreas sparing techniques) and splenectomy is subtotal gastrectomy for antral carcinoma, extended lymphadenectomy remains an important point to improve survival.

To compare extensive with limited lymph node dissection in the surgical treatment of gastric cancer, 320 patients undergoing gastric resection during 1981-1990 were divided into two groups. Although patients undergoing extended lymphadenectomy (n = 157) had a longer operating time (P = 0.0001) and a greater intraoperative blood transfusion requirement (P = 0.009) than those receiving limited dissection (n = 163), the incidence of postoperative complications (22.3 versus 28.2 per cent, P = 0.13) and the hospital mortality rate (3.8 versus 7.4 per cent, P = 0.12) were similar in the two groups. The 5-year survival rate after curative resection (117 and 121 patients after extensive and limited lymph node dissection respectively) was 65.4 versus 50.1 per cent (P = 0.01): 85.9 versus 82.2 per cent for stage I disease (P = 0.60), 66.1 versus 57.8 per cent for stage II (P = 0.82) and 48.7 versus 29.8 per cent for stage III (P = 0.02). Multivariate analysis using the Cox model showed that the extent of lymphadenectomy was an independent prognostic factor for survival (P = 0.01). The results support the value of extensive lymph node dissection in the surgical treatment of gastric carcinoma.

In a consecutive series of 175 patients with gastric carcinoma, 66.8% underwent gastric resection: 74 total gastrectomies with R3 lymphadenectomy and 43 distal subtotal gastrectomies with R2 lymphadenectomy were performed. 73% (86 cases) of resective procedures proved to be "absolute curative" according to Japanese criteria (JRSGC). Nodal involvement was present in 62 out of 117 resected patients (52.9%): 29.9% N1, 9.4% N2, 13.6% N3; a significant relationship (p = 0.012) between depth of invasion of the gastric wall and lymph node metastases was revealed. The hospital mortality after R2-R3 gastrectomy was 4.2%, major surgical complications occurred in 6.8% of cases. The actuarial 5-year survival after curative resection was 59%. The results suggest that extended lymphadenectomy (R2-R3 gastrectomy) is justified in the surgical treatment of gastric cancer; this procedure can be safely performed and permits "absolute curative" resections in a remarkable percentage of cases.