Efficacy after preoperative capecitabine and oxaliplatin (XELOX) versus docetaxel, oxaliplatin and S1 (DOS) in patients with locally advanced gastric adenocarcinoma: a propensity score matching analysis.

BACKGROUND: The aim of this study was to compare the efficacies of the XELOX and DOS regimens as preoperative chemotherapy in patients with locally advanced gastric cancer. METHODS: All cases of locally advanced gastric cancer treated with the XELOX or DOS regimen were reviewed retrospectively. Propensity score matching (PSM) was carried out to reduce selection bias based on age, gender, location, Lauren type, carcinoembryonic antigen level, clinical tumor stage, and clinical node stage. RESULTS: From January 2010 to December 2016, 248 patients were matched; 159 of them received the XELOX regimen and 89 the DOS regimen. The response rates in the XELOX and DOS groups were 34.5 and 38.1%, respectively (P = 0.823). After four cycles of chemotherapy, 111 patients (69.8%) in the XELOX group and 65 patients (73.0%) in the DOS group underwent radical surgery (P = 0.485). The median progression-free survival (33.0 months vs. 18.7 months, P = 0.0356) and the median overall survival (43.8 months vs. 29.1 months, P = 0.0003) were longer for patients who received the DOS regimen than for those who received the XELOX regimen. The occurrence of grade 3 to 4 toxicity was similar in the two groups. CONCLUSIONS: For locally advanced gastric cancer patients, the DOS regimen showed more benefit than the XELOX regimen as preoperative chemotherapy, without any added toxicity effects.

Efficacy of preoperative chemotherapy regimens in patients with initially unresectable locally advanced gastric adenocarcinoma: capecitabine and oxaliplatin (XELOX) or with epirubicin (EOX).

Purpose We assessed the effectiveness of EOX (capecitabine, oxaliplatin and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as preoperative chemotherapy for initially unresectable locally advanced gastric cancer.Methods This is a prospective observational study. Patients with unresectable locally advanced gastric cancer were performed EOX regimen or XELOX regimen at the discretion of the investigators. They were assessed for response every 2 cycles by CT (computed tomography) scan. A multidisciplinary team reassessed resectability after 4 cycles. The primary endpoint was the response rate. Secondary end points included the R0 resection rate, survival and adverse events.Results From November 2008 to May 2015, 242 patients were enrolled; 112 of them were assigned to EOX regimen and 130 to XELOX regimen. The response rates were 33.0% and 33.8% respectively in EOX group and XELOX group (P = 0.997). After 4 cycles of chemotherapy, 63 patients (56.3%) in EOX group and 81 patients (62.3%) in XELOX group received radical operation (P = 0.408). There was no significant difference in progress-free survival (PFS, 12.0m vs. 15.4m, P = 0.925) and overall survival (OS, 25.7m vs. 29.0m, P = 0.783) in two groups. In addition, more adverse effects occurred in EOX group, such as more leucopenia (22.3% vs. 10.0%, P = 0.014), neutropenia (23.2% vs. 11.5%, P = 0.025), fatigue (11.6% vs. 3.8%, P = 0.041) and vomiting (10.7% vs. 2.3%, P = 0.015).Conclusions For unresectable locally advanced gastric cancer patients, XELOX regimen showed similar effects in response rate, radical resection rate and survival benefits, but with less toxicity effects.

Acute acalculous cholecystitis immediately after gastric operation: case report and literatures review.

Acute acalculous cholecystitis (AAC) is a rare complication of gastric surgery. The most commonly accepted concepts regarding its pathogenesis are bile stasis, sepsis and ischemia, but it has not been well described how to identify and manage this disease in the early stage. We report three cases of AAC in elderly patients immediately after gastric surgery, which were treated with three different strategies. One patient died 42 d after emergency cholecystectomy, and the other two finally recovered through timely cholecystostomy and percutaneous transhepatic gallbladder drainage, respectively. These cases informed us of the value of early diagnosis and proper treatment for perioperative AAC after gastric surgery. We further reviewed reported cases of AAC immediately after gastric operation, which may expand our knowledge of this disease.

A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis.

PURPOSE: Gastric cancer with para-aortic lymph node (PAN) involvement is regarded as advanced disease, and only chemotherapy is recommended from the guidelines. In unresectable cases, neoadjuvant chemotherapy could prolong survival if conversion to resectability could be achieved. METHODS: The study was a single-arm phase II trial. Patients who were diagnosed with gastric cancer and PAN involvement (Stations No. 16a2/16b1) were treated with capecitabine and oxaliplatin combination chemotherapy every 3 weeks for a maximum of six cycles. After every two cycles, abdominal computed tomographic scans were repeated to evaluate the response, and surgery was performed at the physician(')s discretion in patients with sufficient tumor response, followed by chemotherapy with the same regimen to complete a total of six cycles. The primary end point was the response rate of the preoperative chemotherapy. The secondary end points were R0 resection rate, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: A total of 48 patients were enrolled. The response rate of the first-line chemotherapy was 49.0 %, and the clinical benefit response was 85.1 %. After a median of four cycles of chemotherapy, 28 patients received surgery (58.3 %). The median PFS and OS of all patients were 10.0 and 29.8 months, respectively. Patients in the surgery group had much longer PFS (18.1 vs. 5.6 mo, P = 0.001) and OS (not reached vs. 12.5 mo, P = 0.016) compared with those in the non-surgery group. CONCLUSIONS: For gastric cancer patients with PAN involvement, neoadjuvant chemotherapy with XELOX demonstrated a good response rate, and a sufficient R0 resection rate, with acceptable toxicities. Further study is needed to confirm the effectiveness of this regimen.

[Clinicopathological features and prognosis of chronic gastric ulcer with early canceration].

OBJECTIVE: To evaluate the clinicopathological features and prognosis of chronic gastric ulcer with early canceration in order to provide useful information for diagnosis and treatment strategies. METHODS: A retrospective review of clinical data and prognosis from 43 patients of chronic gastric ulcer with early canceration from 2003 to 2010 was conducted. These data were compared with those with primary intra-mucosa gastric cancer (type I and II 275 cases, type III 68 cases). RESULTS: In 43 cases of chronic gastric ulcer with early canceration, 30 cases (69.8%) were male, 22 cases (51.2%) were younger than 60 years old. Lesions located in the body or antrum of the stomach in 39 cases (90.7%), were less than 2 cm in 26 cases (60.5%), were undifferentiated type in 23 cases (53.5%), and developed lymph node metastasis in 4 cases (9.3%). Lesions of 4 cases of chronic gastric ulcer with early canceration located in the upper third of the stomach, while those of type III primary intra-mucosal gastric cancer all located in the lower two thirds, and the difference was statistically significant (P<0.01). Compared to type III and type I and II primary intra-mucosal gastric cancer, chronic gastric ulcer with early canceration did not differ in clinicopathological characteristics such as histological type, vascular or lymphatic invasion, and lymph nodes metastasis (all P>0.05). The median follow-up time was 57 months (range 16 to 98 months). The 5-year overall survival was 95.3% in chronic gastric ulcer with early canceration group, similar to that of type I, II (97.4%) or type III (94.5%) primary intra-mucosal gastric cancer group (P>0.05). CONCLUSIONS: The clinicopathological features of chronic gastric ulcer with early canceration are similar to those of primary intra-mucosal gastric cancer. The prognosis is promising for those patients undergoing surgical treatment.

[Efficacy of neoadjuvant chemotherpy in patients with locally advanced gastric cancer].

OBJECTIVE: To evaluate the efficacy and safety of neoadjuvant chemotherapy in patients with locally advanced gastric cancer, and to analyze the relevant factors of recurrent death of gastric cancer after adjuvant chemotherapy. METHODS: Clinical data of 49 patients who underwent neoadjuvant chemotherapy for locally advanced gastric cancer between July 2007 and June 2011 were reviewed. Preoperative staging was determined by endoscopic ultrasonography and abdominal computer tomography (CT) or magnetic resonance imaging (MRI). Chemotherapy was administered for regimen of two or three drugs. Prognostic factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model. RESULTS: The response rate was 33.3% (16/48) and disease control rate was 93.8% (45/48). Forty-four (89.8%, 44/49) patients received curative resection after neoadjuvant chemotherapy, among whom 90.9% (40/44) underwent D2 lymphadenctomy. Thirty-two cases had pathological response and 2 patients had pathological complete response. The average hospital stay was 11.6 days and 2 patients had longer hospitalization because of postoperative pancreatic complications. The toxicities were most in grade 1-2. All the patients were followed up postoperatively and the median follow-up was 21.6 months. Median progression-free survival was 29.6 (95%CI:24.0-35.2) months and median overall survival was 34.6 months (95%CI:29.8-39.4). Imaging response (P=0.038, RR=0.168, 95%CI:0.031-0.904) and pathological response (P=0.007, RR=0.203, 95%CI:0.064-0.642) were identified as independent prognostic factors with COX multivariate analysis. CONCLUSIONS: Neoadjuvant chemotherapy has quite high disease control rate and R0 resecting rate for patients with locally advanced gastric cancer. Imaging response and pathological response are most important prognostic factors in those patients.

[Association of transcriptional repressor Snail with Lauren classification of gastric cancer].

OBJECTIVE: To explore the association of Snail expression and Lauren classification of gastric cancer. METHODS: The protein levels of Snail and E-cadherin were detected by Western blot in N87 (intestinal-type gastric cancer cell line) and AGS(diffuse-type gastric cancer cell line) cell lines and those after transfection of GSK-3ß plasmid. The study included a total of 77 patients with primary gastric cancer who underwent curative gastrectomy in the Zhongshan Hospital from February 2000 to December 2005 without any chemotherapy or radiation therapy before surgery. Tissues of gastric cancer specimens were stained using immunohistochemistry to determine Snail expression. RESULTS: Snail expression was low in N78 and high in AGS. E-cadherin expression showed reverse expression pattern. After transfection with GSK-3ß, the expression of Snail was significantly suppressed and that of E-cadherin elevated (P<0.01). Different concentrations of GSK-3ß inhibitor lithion chloride were used to treat the cell lines and Snail expression was significantly up-regulated in a dose-dependent manner (P<0.01). Snail expression was elevated in 16 out of 21 N78 cell lines, and in 21 out of 56 AGS cell lines, and the difference was statistically significant (P<0.01). CONCLUSION: The expression of Snail is closely associated with the Lauren classification of gastric cancer, and it may be a potential marker of the gastric cancer classification.

[Association of T helper cell 1 cytokines expressions with prognosis of gastric cancer patients].

OBJECTIVE: To investigate the association of the expressions of Th1 cytokines in gastric cancer tissue and the prognosis of patients with gastric cancer after radical resection. METHODS: Fifty-eight patients with gastric cancer treated at the Zhongshan Hospital of Fudan University were retrospectively analyzed. The expressions of Th1 cytokines mRNA were detected in tumor tissues by real-time polymerase chain reaction(RT-PCR) method in Th1 cells including TRAV10, IRF1, TBX21, CD3Z, GZMB, GATA3, and IFNG. Association of Th1 cytokines mRNA expressions and prognosis was evaluated. RESULTS: The median follow up was 42.5(1-64) months. The 1-year survival rate was 84.5% and the 3-year survival rate was 72.4%. Univariate Cox regression analysis showed that lymph node metastasis, distant metastasis, TNM staging, lymphovascular invasion, GNLY mRNA expression, and the overall expression level of the 8 types of Th1 cells were associated with the prognosis of patients with gastric cancer(all P<0.05). The 3-year survival was 86.2% in patients with increased expression of mRNA and 58.6% in those with decreased expression. The 3-year survival was 79.6% in patients with any increase in the 8 Th1 cytokines and 33.3% in those with consistent downregulation of the 8 cytokines. Multivariate Cox analysis showed that lymph node metastasis and the overall expression level of 8 Th1 cytokines were independent risk factors associated with the prognosis of patients with gastric cancer in this cohort(both P<0.05). CONCLUSIONS: The mRNA expression of GNLY is associated with the prognosis of patients with gastric cancer but is not an independent risk factor. The combination of mRNA expressions of the eight cytokines is an independent prognostic factor.

[Adjuvant chemotherapy for gastric cancer: more drugs do not mean better efficacy].

OBJECTIVE: To compare oncologic outcomes between doublet and triplet adjuvant chemotherapy for gastric cancer patients undergoing radical resection. METHODS: Patients with gastric cancer receiving adjuvant chemotherapy after radical resection from January 2004 to December 2008 were included. Doublet was defined as 5-FU 750 mg/m² (days 1-5) or capecitabine 1000 mg/m² (days 1-14) plus cisplatin 60 mg/m² (day 1) or oxaliplatin 130 mg/m² (day 1), while triplets had epirubicin 50 mg/m² (day 1) added. Chemotherapy was initiated 4-6 weeks after surgery, repeated every three weeks for 6 cycles. Patients were followed-up in the outpatient clinic until death or the most recent follow up(April 30, 2010). Cox proportional- hazard model and Chi-square test were used to test statistical difference. RESULTS: A total of 316 patients (210 received doublets, 106 received triplets) had a median follow-up time of 47 months. Seventy-seven patients died at the end of the follow-up. Two groups were comparable except for age (median age of 57 in doublets, 51 in triplets, P<0.01). The two groups had similar disease-free survival (16 months vs. 23 months, P=0.656) and 3-year overall survival(59.6% vs. 64.8%, P=0.293). There was no significant difference in severe adverse side effects between the two groups (21.9% vs. 30.2%, P=0.107). CONCLUSION: Triplet adjuvant chemotherapy appears not to be associated with superior efficacy than doublet regimen for patients with gastric cancer after radical resection.

[Expression and prognostic value of M2 macrophages and regulatory T cells in gastric carcinoma tissue].

OBJECTIVE: To explore the prognostic value of M2 macrophages and regulatory T cells(Tregs) in gastric carcinoma. METHODS: Clinicopathological characteristics and follow up data of 135 patients with gastric carcinoma were collected. Patients included were those who underwent D2 radical resection(R0) at Zhongshan Hospital of Fudan University from February 1999 to December 2005. Tissue chips of gastric carcinoma specimen were stained using immunohistochemistry to determine the cells density and number of M2(CD163 positive) and Tregs(Foxp3 positive). RESULTS: The median positive cells density of M2 macrophages and Tregs in tumor tissue were 7.48/HP and 6.33/HP, respectively, higher than that in adjacent tissues(1.37/HP and 2.92/HP, P<0.001). The density of M2 macrophages was positively correlated with that of Treg cells(r=0.415, P<0.001) in tumor tissue. The median survival of patients with low expression of M2 and Tregs(n=43) was significantly longer than those with high expression of the 2 cells(n=45) (99.0 vs. 72.3 months, P<0.05). CONCLUSION: Combined detection of M2 macrophages and Tregs may predict the prognosis of gastric carcinoma.

[Risk factors for postoperative pancreatic leakage after D(2) resection of gastric cancer].

OBJECTIVE: To investigate the incidence of pancreatic fistula following D(2) gastrectomy and associated risk factors. METHODS: A total of 132 consecutive cases of gastric cancer underwent D(2) gastrectomy between Jul 1, 2009 and Dec 2009. Amylase concentration of the drainage fluid and serum amylase concentration were tested on day 1, 4, 7 after operation. Univariate analyses were performed to evaluate the significance of various covariates as risk factors for the pancreatic fistula-related complications. RESULTS: The incidence of pancreatic fistula was 17.4%. None of the following factors including age, gender, tumor location, tumor stage, N stage, range of resection, fistula output, and serum amylase were associated with pancreatic fistula. CONCLUSION: The incidence of pancreatic fistula following D(2) gastrectomy is high. Drainage tube is necessary to prevent serious complications.

[Da Vinci robot-assisted gastrectomy with lymph node dissection for gastric cancer: a case series of 9 patients].

OBJECTIVE: To evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy(RAG) with lymphadenectomy using the Da Vinci system. METHODS: A total of 9 patients in our institute from March 17 to April 24 2010 underwent RAG. Clinicopathologic characteristics and surgical outcomes were summarized. RESULTS: All operations were performed successfully without conversion to either open or laparoscopic approach. There were 5 total gastrectomies,2 distal gastrectomies, 1 proximal gastrectomy and 1 wedge gastrectomy with D(1) or D(2) lymphadenectomy. The total operative time was 150 to 440 minutes. Total blood loss ranged from 10 to 100 ml. The ranges of harvested lymph nodes were 19-24 for D(1) patients and 28-38 for D(2) patients. There was 1 case of postoperative gastric leakage, which were managed conservatively. CONCLUSIONS: RAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer.

[Evaluation the value of number of metastatic perigastric lymph nodes on prognosis in patients with gastric cancer].

OBJECTIVE: To find out a simple and reproductive prognostic index in gastric cancer patients,which can be used as a comparable parameter among different regions of China. METHODS: The perigastric metastatic lymph nodes(PGMLN) with long-term survival data were retrospectively evaluated in 148 gastric cancer patients, undergone potentially curative resections. RESULTS: The 3-year cumulative survival rate was 62.8% and the survival rate decreased significantly with the increase of PGMLN, especially when the PGMLN was more than 6. The PGMLN had a clear linear relationship with total positive lymph nodes(r=0.94, P<0.01), while it had little correlation with total resected lymph nodes(r=0.18,P=0.2). CONCLUSIONS: PGMLN is a convenient and reliable prognostic factor in gastric cancer patients, which may be a good candidate of comparable parameters among different regions of China.