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Aim: To compare anatomical with numerical criterion to measure the quality of lymphadenectomy for gastric cancer., Patients and Methods: We analyzed 447 gastric cancer patients with resectable tumor stage (R0 resection) with at least 16 examined lymph nodes., Results: Of 447 patients, 82.6% underwent D2 lymphadenectomy for a median of total examined lymph nodes of 28. The 7-year disease-specific survival rate for the whole sample was 71.4%. Survival was significantly different between patients treated with D2 and D1 lymphadenectomy (77.4% versus 44.3%; p < 0.001) and between patients with total examined lymph nodes ≥ 28 and < 28 (74.5% versus 62.3%; p = 0.041). Anatomical criterion significantly differentiated 7-year survival in patients stratified according to a numerical parameter., Conclusion: We should still consider the anatomical criterion as the best item to measure the quality of lymphadenectomy for gastric cancer.

Introduction: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery., Methods: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated., Results: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors., Conclusions: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival., (© 2018 S. Karger AG, Basel.)

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.

In the last years, the concept of 'enhanced recovery after surgery' (ERAS) has become a routine in the perioperative care of patients undergoing colorectal resection. The application of ERAS programs in gastric surgery had a more difficult penetration into clinical practice, mainly for the introduction of radical changes in the traditional postoperative management. The aim of the study was to analyze the rate of compliance to a standardized ERAS protocol in different Italian centers and evaluate the results in terms of postoperative outcomes. From April 2015 to July 2017, a prospective observational study was conducted among seven centers participating in the Italian Group for Research for Gastric Cancer (GIRCG), in patient candidates to elective gastrectomy for cancer. A standardized ERAS perioperative protocol was approved by all centers. Compliance to the protocol was then evaluated and postoperative outcomes (morbidity and mortality rate, duration of hospital stay and readmission rate) were analyzed. Two-hundred and seventy unselected patients operated on for gastric cancer were enrolled. The median age was 73 years; 40.4% of patients were female; 24.1% had a nutritional risk score ≥ 3. Perioperative chemotherapy was used in 23.7% of cases. Total gastrectomy was performed in 57.4% of patients; minimally invasive approach was adopted in 28.1% of patients. Adherence to the protocol varied between 23 and 88% for single items. It was quite low for pre- and intraoperative items, mainly for items related to nutritional care. Postoperative complications occurred in 35.5% of patients, mortality was 0.7%. Median length of hospital stay was 8 days (range 4-72) and the readmission rate was 6.3%. There is a growing attention on the implementation of ERAS protocol for gastric cancer surgery, but several elements of this protocol are still not routinely adopted, among them items regarding nutritional care.

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

Aims and Background: The role of neoadjuvant (NAD) chemotherapy (CHT) in patients with locally advanced gastric cancer (LAGC) is validated. However, some important limitations emerged from the literature, including patient selection, quality of surgery, and pathologic response evaluation. Neoadjuvant CHT for LAGC has been evaluated with a focus on safety and efficacy of the preoperative approach in terms of patient compliance, surgical outcomes, and pathologic response., Methods and Study Design: Ninety-one patients with gastric adenocarcinoma were prospectively observed. All patients received computed tomography scan and laparoscopy staging. Ten patients with LAGC (including 2 with LAGC suspected for cM+/lapM+) had been recruited in the preoperative ECF/EOX CHT protocol and were compared with 61 patients who underwent surgery alone., Results: The overall compliance for the preoperative CHT group was higher than compliance for adjuvant CHT observed in both the NAD CHT group and the surgery alone group. There were 2 treatment shifts to FOLFOX in the preoperative regimen. In the preoperative CHT group, D2-gastrectomy was possible only in 6/10 of cases, with a R0 resection rate of 67% (versus 64% in the LAGC patients treated by surgery alone). The postoperative mortality and morbidity were 0% and 17% in the NAD CHT group versus 2% and 26% in the surgery alone group. The overall pathologic response rate after NAD CHT was 83% (5/6)., Conclusions: Staging and CHT management problems can negatively affect patient outcomes. In the LAGC setting, when well applied, NAD CHT could be considered a valuable treatment option.

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: This study was designed to analyze the prognostic significance of the staging system based on the ratio of metastatic lymph nodes (TRM) compared with the TNM staging system in patients with gastric cancer., Methods: We reviewed the data of 219 patients who underwent gastrectomy for node-positive M0 cancer. Node Ratio (NR) categories (NR1: 1-15%; NR2: 16-40%; NR3: >40%) were determined by the best cutoff approach at log-rank test. After confirming the prognostic validity of NR in a collinearity-free Cox regression analysis, among different combinations of pT and NR categories we selected five prognostically homogeneous TRM classes. To compare the prognostic power of the TRM vs. TNM systems, we plotted TRM and TNM classes against the mortality estimates., Results: Both of the TRM and TNM classifications significantly stratified patients outcomes (p < 0.0001), but the TRM system identified prognostic subgroups more homogeneous than the TNM system., Conclusions: The TRM staging system is a simple and reliable tool to stratify patients with gastric cancer and has a higher prognostic power than the current system.

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case-control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98-2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07-5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05-4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12-7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individual's susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.

Sulfotransferases (SULT) catalyse both the bioactivation and detoxification of a wide range of promutagens and carcinogens. The SULT1A1 gene possesses a G-->A polymorphism that results in a Arg to His substitution at codon 213, and the His allele has been shown to have a low activity and thermal stability. To test the hypothesis that individuals carrying the variant allele may be at high risk of gastric cancer, we identified the SULT1A1 Arg213His genotype by a PCR-based RFLP in a preliminary study of 76 gastric adenocarcinoma patients that underwent curative gastrectomy and 260 age and sex-matched controls from a medical centre in Rome. A comprehensive epidemiological interview was conducted on all participants to collect lifestyle data. The prognostic significance of the SULT1A1 Arg213His polymorphism with respect to staging, differentiation and histological type of gastric cancer was also evaluated. The frequencies of His/His in cases and controls were 11.9% (9/76) and 5% (13/260), respectively (P=0.025). After adjusting for substance use, age, gender and physical activity, individuals with His/His showed a 3.32 fold increased risk of developing gastric cancer compared to those with Arg/Arg (95% CI=1.17-9.45). This positive association was more pronounced amongst males, alcohol drinkers, current smokers and consumers of grilled/barbecued meat and, unexpectedly, amongst individuals with a high intake of fruit. A statistically significant association was also found between the diffuse type of gastric cancer and the heterozygous SULT1A1 genotype. Our preliminary findings suggest for the first time that the SULT1A1 His213 allele may be important in the development of gastric cancer, with other factors modulating such effect.