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T1b gallbladder carcinoma (GBC) is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver. However, controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection.To explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades.Patients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were used to analyze the overall survival (OS) and disease-specific survival (DSS) of patients with T1b GBC of different pathological grades. Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis.Of the 528 patients diagnosed with T1bN0M0 GBC, 346 underwent simple cholecystectomy (SC) (65.5%), 131 underwent SC with lymph node resection (SC + LN) (24.8%), and 51 underwent radical cholecystectomy (RC) (9.7%). Without considering the pathological grade, both the OS (Simple cholecystectomy may be an adequate treatment for grade I T1b GBC, whereas more extensive surgery is optimal for grades II-IV T1b GBC.

To investigate the clinical significance of hepatic parenchyma incision by lithotomy near the second hepatic portal area for the treatment of complex hepatolithiasis. A retrospective study was conducted with 35 patients who had complicated hepatolithiasis in our hospital from January 2008 to December 2013, who underwent hepatic parenchyma incision by lithotomy near the second hepatic portal area. The perioperative and long-term outcomes included the stone clearance rate, operative morbidity and mortality, and the stone recurrence rate. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded from the study. All patients with hepatic duct stones were mainly located at S2, S4, and S8 regions. Surgical methods included were hepatic parenchyma incision by lithotomy near the second hepatic portal area, or by combined partial hepatectomy. The mean follow-up period was 51 months. One patient died during hospitalization. The surgical morbidity was 17.6%, stone clearance rate was 88.2%, and final clearance rate was 94.1% followed by postoperative choledochoscopic lithotripsy. The stone recurrence rate was 15.6% and the occurrence of postoperative cholangitis was 11.8% during the follow-up period. Hepatic parenchyma incision by lithotomy near the second hepatic portal area is safe with satisfactory short and long-term outcome results for complicated hepatolithiasis.

Peritoneal metastasis is a major cause of death in patients with advanced gastric carcinoma. DJ-1 is now considered to play an important role in the metastasis of various malignancies. However, it remains largely unclear whether DJ-1 is involved in the development of peritoneal metastasis by gastric carcinoma. In the present study, we showed that the expression of DJ-1 was significantly upregulated in gastric cancer specimens with peritoneal metastasis compared to those without peritoneal metastasis. Knockdown of DJ-1 expression significantly inhibited invasion and migration, in vitro and the in vivo peritoneal metastatic abilities of SGC7901 gastric cancer cells. Moreover, knockdown of DJ-1 also diminished the expression of matrix metallopeptidase (MMP)-2 and MMP-9. All of these effects were reversed by restoration of DJ-1 expression. Following investigation of the pathway through which DJ-1 regulates cell invasion and migration, DJ-1 was found to cause phosphorylation of Akt in SGC7901 gastric cancer cells. Inhibition of the Akt pathway in SGC7901 cells mimicked the effects of DJ-1 knockdown on cell migration, invasion, MMP-2 and MMP-9 expression, and abolished the effects of DJ-1 in promoting SGC7901 cell invasion and migration. Taken together, the present study revealed that DJ-1 plays an important role in the development of peritoneal carcinomatosis from gastric carcinoma, at least partially through activation of the Akt pathway and consequent upregulation of MMP-2 and MMP-9 expression. Thus, DJ-1 may be a potential therapeutic target for peritoneal carcinomatosis of gastric carcinoma.

The primary concern regarding laparoscopic hepatectomy in hepatolithiasis patients is surgical safety, which may be high in current practice.Hepatolithiasis patients who underwent laparoscopic and laparotomic hepatectomies were retrospectively studies after being matched for age, location of gallstones, liver resection and underlying liver conditions at a ratio of 1:1 (n = 44 in each group). The rates of intraoperative incidents and postoperative complications were examined using validated classification and grading systems. The primary outcome measure was the procedure-related complication/mortality rate.Laparoscopy was converted to open surgery in three patients (6.8 %). The length of the operation for laparoscopic hepatectomy was significantly longer than that for laparotomic hepatectomy (277.5 min [range, 190-410 min] vs. 212.5 min [140-315 min], P0.001). The two groups had similar intraoperative blood loss (367.5 mL [150-1200 mL] vs. 392.5 mL [200-1400 mL], P0.05) and transfusion frequencies (13.6 vs. 18.2 %, P0.05). The laparoscopy group had a higher percentage of patients with at least one intraoperative incident compared with the laparotomy group (22.7 vs. 6.8 %; P0.05). Vascular events occurred in nine patients (20.5 %) undergoing laparoscopy and two patients (4.5 %) undergoing laparotomy (OR 5.4 [95 %CI, 1.1-26.7], P0.05).Laparoscopic hepatectomy is associated with a higher risk of intraoperative vascular incidents in hepatolithiasis patients compared wit laparotomy.

Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133+/CD44+ CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs. Interestingly, the level of mitochondrial superoxide was detected to be significantly lower in CSCs than in parental cells after DXR treatment. Furthermore, the mitophagy level and expression of BNIP3L, a mitophagy regulator, were significantly higher in CSCs than in parental cells after DXR treatment. Silencing BNIP3L significantly halted mitophagy and enhanced the sensitivity to DXR in CSCs. Our data suggested that mitophagy, but not non-selective autophagy, likely contributes to drug resistance in CSCs isolated from HCT8 cells. Further studies in other cancer cell lines will be needed to confirm our findings.

In addition to sprouting angiogenesis, other mechanisms, such as mosaic tumor vessel formation, have been recognized to contribute to tumor vascularization. We sought to examine vascular alteration as well as tumor growth inhibition after treatment with antiangiogenic therapy, chemotherapy alone or in combination.Hepatocellular carcinoma cells (Hep3B) expressed green fluorescent protein were utilized to establish orthotopic xenograft model in nude mice. The formation and distribution of mosaic vessels was analyzed quantitatively by immunolabeling. Next, changes in tumor microcirculation and therapeutic effects on tumor growth were evaluated in several different treatment groups: control, conventional doxorubicin, metronomic doxorubicin, bevacizumab, bevacizumab plus conventional doxorubicin, and bevacizumab plus metronomic doxorubicin. In addition, we examined the effects of combined regimens on lung metastasis using a highly metastatic human hepatocellular carcinoma (HCCLM3) mouse model.Approximately 62 % of the vessels were present in the central part or near the midsection of the tumor and were mosaic. Only the combined antiangiogenic treatment and chemotherapy (metronomic schedule, P = 0.00; conventional schedule, P = 0.02) had a significant effect on the degree of mosaic vasculature. Metronomic doxorubicin in combination with bevacizumab had an even more profound effect than bevacizumab plus conventional doxorubicin (P0.05) on tumor growth inhibition and survival. However, bevacizumab plus metronomic doxorubicin failed to inhibit lung metastasis compared with antiangiogenic monotherapy.Metronomic chemotherapy in combination with antiangiogenic treatment results in the reduction of mosaic tumor vasculature, inhibition of tumor growth, and enhanced survival of mice. Further investigation of drug scheduling is required to optimize antitumor activity.

Associations between five polymorphisms of vascular endothelial growth factor (i.e., VEGF +936C/T, -1154A/G, -2578C/A, -634G/C and -460T/C) and risk of breast cancer have been extensively studied, and the currently available results are inconclusive. Therefore, we performed this meta-analysis to further study the associations. The databases of Pubmed, Embase and CNKI were retrieved up to April 1st, 2010. The pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 10 case-control studies with 8175 cases and 8528 controls were included in this study. The overall results of combined analyses showed that five polymorphisms of VEGF were not associated with risk of breast cancer [ORs (95% CIs): 1.03 (0.84-1.27) for CC vs. TT for +936C/T, 0.95 (0.81-1.12) for AA vs. GG for -1154A/G, 1.01 (0.90-1.14) for CC vs. AA for -2578C/A, 1.02 (0.90-1.16) for GG vs. CC for -634G/C and 0.86 (0.68-1.09) for TT vs. CC for -460T/C]. When subgroup analyses by ethnicity for VEGF +936C/T and -634G/C, the results suggested that +936C/T was not associated with the risk of breast cancer for either Asians [1.40 (0.92-2.13) for CC vs. TT and CC+CT vs. TT: 1.38 (0.91-2.10) for CC+CT vs. TT] or Caucasians [0.93 (0.73-1.19) for CC vs. TT and 0.91 (0.72-1.16) for CC+CT vs. TT], and -634G/C was not associated with the breast cancer for Caucasians [1.07 (0.92-1.24) for GG vs. CC and 1.05 (0.91-1.21) for GG+GC vs. CC]. In addition, when excluding one study, which was out of Hardy-Weinberg equilibrium for VEGF +963C/T and whose controls were from both patients and healthy people, the negative results were also persistent, and ORs (95% CIs) were 1.04 (0.84-1.29) for CC vs. TT, 1.03 (0.83-1.27) for (CC+CT) vs. TT. This meta-analysis suggests that the VEGF +936C/T, -1154A/G, -2578C/A, -634G/C and -460T/C may be not associated with risk of breast cancer development based on the currently available studies, especially for Caucasians. More well designed studies with larger sample size on different ethnicities are needed to further assess the associations.

Objective To investigate the association between potentially functional MDM2 oncogene, E3 ubiquitin protein ligase ( MDM2) T309G polymorphism and susceptibility to oesophageal or gastric cancer. Methods Two investigators independently searched the PubMed and Chinese National Knowledge Infrastructure databases for studies published before September 2013. Results Pooled results showed that the variant homozygous 309GG genotype (versus TT) was significantly associated with increased risk of both oesophageal (odds ratio [OR] 0.77; 95% confidence interval [CI] 0.65, 0.90) and gastric cancer (OR 0.52; 95% CI 0.38, 0.72). Subgroup analysis revealed a 309GG-associated increased risk for both cancer types in Asian populations, particularly among Chinese and Japanese ethnicity. When stratified for Helicobacter pylori infection and histological type of gastric cancer, the 309GG-related risk was higher in H. pylori-positive patients (T versus G: OR 0.37; 95% CI 0.22, 0.63) and the association was stronger with intestinal (TT + TG versus GG: OR 0.68; 95% CI 0.54, 0.87) rather than diffuse gastric-cancer type. Conclusions The MDM2 T309G polymorphism may be significantly associated with increased susceptibility to oesophageal or gastric cancer, particularly among Eastern Asian populations.

To evaluate the efficacy of laparoscopic total mesorectal excision (laparoscopic TME) versus open total mesorectal excision (open TME) in the treatment of middle and low rectal cancer using meta-analysis.From 1991 to 2012, the Chinese and English articles of randomized controlled trails (RTCs) about laparoscopic TME versus open TME in the treatment of middle and low rectal cancer were collected, and a meta-analysis was performed with RevMan 5.1 software.Eight RCTs including 863 patients with middle and low rectal cancer (428 cases in laparoscopic TME group, 435 cases in open TME group) were enrolled in the meta-analysis. Laparoscopic TME was associated with significantly less intraoperative blood loss (P0.01), earlier to pass first flatus (P0.01), shorter hospital stay (P0.05), less postoperative incision infections (P0.01) and postoperative bleeding (P0.05) compared to open TME. There were no significant differences between laparoscopic TME and open TME groups in operative time, number of resected lymph nodes, anastomotic leak, ileus and pelvic abscess (all P0.05).As compared to open TME, laparoscopic TME has similar efficacy in terms of lymph nodes harvest, and it can promote postoperative recovery, and reduce incision infection and postoperative bleeding.

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.

Background and Aims The relationships between P53 Arg72Pro and risks of digestive tract cancers have been extensively studied, and conclusive results were unavailable. Methods Fifty three case-control studies were included through searching the databases of Medline, Embase and CNKI (up to August 2010). The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the associations. Results The results showed that there were no overall associations between P53 Arg72Pro and risks of digestive tract cancers. Subgroup analyses showed that P53 Arg72Pro was associated with risk of gallbladder and pancreatic cancer (OR [95% CI]: 1.44 [1.13-1.83] for Pro carriers vs. ArgArg). In addition, subgroup analyses also suggested that the Pro allele was associated with increased risks of digestive tract cancers among Asians (1.19 [1.01–1.42] for ProPro vs. ArgArg). Meanwhile, Pro allele was also suggested to be associated with increased risk of gastric cancer (1.33 [1.02–1.74] for ProPro vs. ArgPro for diffuse type of gastric cancer and 1.29 [1.05–1.57] for ProPro vs. Arg carriers for gastric cardia cancer) and colorectal cancer (1.26 [1.05–1.51] for ProPro vs. ArgPro for population-based case-control studies; 1.43 [1.09–1.87] for ProPro vs. ArgArg for colon cancer; 1.49 [1.09–2.06] for ProPro vs. ArgArg for rectal cancer and 2.22 [1.44–3.44] for ProPro vs. ArgArg for early stage of colorectal cancer). Conclusions This meta-analysis suggests that Pro allele in P53 Arg72Pro is significantly associated with the increased risks of digestive tract cancers, especially for Asians, and for gastric cancer, colorectal cancer and gallbladder and pancreatic cancer.