Prevention of anastomotic leakage after low anterior resection in rectal cancers.

BACKGROUND/AIMS: To review the available data on the efficacy of the measures that are directed towards prevention of anastomotic leakage after low anterior resection and introduce a promising method based on our own experience. METHODOLOGY: The Medline database was searched for studies on the prevention of anastomotic leak after low anterior resection in rectal cancers. RESULTS: Two meta-analyses of the results indicate that a routine defunctioning stoma reduces the rate of clinically relevant anastomotic leakages and is thus recommended in such patients. However, the morbidity of the stoma itself, as well as the morbidity and mortality of its closure should also be considered and pending further trials to clarify its role. Studies suggested that omentoplasty may reduce the leakage rate, but there is a paucity of large randomized trials. A non-randomized trial together with our clinical experience indicated Valtrac-secured intracolonic bypass (VIB) may be a promising method in prevention of anastomotic leakage in rectal cancers. CONCLUSIONS: VIB appears so far to be a promising method for the prevention of anastomotic leak after low anterior resection in rectal cancers. However, further randomized controlled studies are still required to determine its clinical efficacy.

Ulcerated epithelioid hemangioendothelioma of the right armpit in childhood.

Epithelioid hemangioendotheliomas are unique vascular tumors characterized by epithelioid or histiocytoid endothelial cells that mainly affect adults. This low-grade malignant vascular tumor was described as a distinctive condition in 1982 by Weiss and Enzinger. Although the tumor is classified in between an angiolymphoid hyperplasia with eosinophilia and an epithelioid angiosarcoma, it sometimes takes a clinical course resembling that of angiosarcoma. We describe that case of a 12-year-old boy who presented with an approximately 6-month history of a spontaneous chronic lesion in his right armpit and became a painful ulceration in the prior 2-month period. The histopathologic examination revealed small nests and cords of spindling epithelioid endothelial cells, intracytoplasmic lumina containing erythrocytes, pinocytotic vesicles and a necrotic area. Immunohistochemical staining was positive for the endothelial markers CD31, CD34, CK(+), and vim(+). On the basis of these findings the diagnosis of EHE was made. After surgery, pathologic examination revealed metastasis in the lymph nodes. So polychemotherapy was started. As our case report shows, it is possibility that cutaneous ulceration of a malignant tumor such as EHE should be considered, even in children.

siRNA directed against TrkA sensitizes human pancreatic cancer cells to apoptosis induced by gemcitabine through an inactivation of PI3K/Akt-dependent pathway.

Previously, we have documented that the aggressive and highly metastatic behavior of pancreatic cancer may be due to the aberrant expression of nerve growth factor (NGF) and its high-affinity receptor, proto-oncogene TrkA. In this study, we sought to determine the effect of suppressing TrkA expression on pancreatic cancer chemosensitivity to gemcitabine. Human pancreatic cancer cell lines PANC-1, MIA-PaCa-2 and ASPC-1 were studied. The expression and kinase activity of TrkA were determined by Western blot analysis and in vitro kinase assay respectively. RNA interference was used to suppress TrkA expression. Gemcitabine-induced cytotoxicity was determined by tetrazolium reduction assay and caspase profiling was performed. The effect of TrkA-specific siRNA on PI3K/Akt activity was also quantified. TrkA expression and kinase activity in cell lines were directly correlated with gemcitabine chemoresistance. TrkA-specific siRNA suppressed TrkA expression and kinase activity, and furthermore increased gemcitabine-induced, caspase-mediated apoptosis. PI3K/Akt activity was decreased by suppression of TrkA expression. Taken together, these data demonstrated that TrkA is a determinant of pancreatic adenocarcinoma chemoresistance and PI3K/Akt is a key signaling component by which NGF activation of the TrkA signal transduction pathway protects pancreatic cancer cells from chemotherapy-induced cell death.

Geldanamycin destabilizes HER2 tyrosine kinase and suppresses Wnt/beta-catenin signaling in HER2 overexpressing human breast cancer cells.

HER2 (also known as ErbB2) is a transmembrane tyrosine kinase whose surface overexpression is linked to tumorigenesis and poor prognosis in breast cancer patients. beta-catenin is a substrate of this kinase, and HER2-dependent phosphorylation of tyrosine 654 leads to dissociation of the E-cadherin-beta-catenin membrane complex and increased Wnt signaling. beta-catenin-mediated Wnt signaling promotes proliferation and invasion of breast cancer cells. In this study, we show that HER2 binds to beta-catenin and that geldanamycin (GA), a drug that destabilizes HER2 protein, causes rapid depletion of HER2, thereby disrupting its association with beta-catenin in SKBr3 human breast cancer cells. Interestingly, GA did not affect the stability of beta-catenin protein, but altered its subcellular localization, driving it out of the nucleus and increasing its association with E-cadherin. Importantly, the change in subcellular localization of beta-catenin was also associated with a significant decrease in proliferation and motility of GA-treated breast cancer cells. Moreover, GA treatment led to reduced expression of the Wnt signaling target and cell cycle-promoting gene cyclin D1, providing a potential mechanism for the reduced proliferation. In conclusion, GA treatment suppressed tumorigenicity in the human breast cancer cell line SKBr3, at least in part through destabilization of the HER2 oncoprotein and repression of the Wnt/beta-catenin signaling pathway. These findings provide evidence for the clinical importance of GA in treatment of HER2 overexpressing breast cancers.

Predictors of systemic chemotherapy contraindication in pancreatic cancer patients with distant metastasis.

BACKGROUND/AIMS: To investigate predictors of systemic chemotherapy contraindication in pancreatic cancer patients with distant metastasis. METHODOLOGY: Eighty-seven consecutive pancreatic cancer patients with distant metastasis receiving systemic chemotherapy using 5-fluorouracil, cisplatin or gemcitabine were analyzed retrospectively to investigate prognostic factors. RESULTS: The overall median survival time of all patients in the whole series was 3.8 months, the 3-, 6, and 12-month probability of survival being 58%, 26%, and 3%, respectively. Significant poor prognostic factors were the age of 65 years old or older, presence of ascites, a total bilirubin > 2.5 mg/dL, ChE <110 IU/L, a higher level of tumor maker (CA19-9) and performance status <80 (p < 0.005). Cox proportional hazards model revealed independent poor prognostic factors were a presence of ascites, serum ChE level <110 IU/L, and age > or =65. A prognostic index was calculated based on the regression coefficients derived from the three variables according to their relative risk of death (RRD) = exp (presence of ascites x 1.213 + serum ChE level x 1.065 + age > or = 65 x 0.651). CONCLUSIONS: Ascites, ChE <110 IU/L, or age > or =65 should be chemotherapy contraindications for pancreatic cancer patients with distant metastasis because of their extremely short survival time and some other experimental approaches or supportive care are needed.

Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis.

BACKGROUND: Compared with open oesophagectomy (OE), minimally invasive oesophagectomy (MIO) proves to have benefits in reducing the risk of pulmonary complications for patients with resectable oesophageal cancer. However, it is unknown whether MIO has superiority in reducing the occurrence of in-hospital mortality (IHM). OBJECTIVE: The objective of this meta-analysis was to explore the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM). DATA SOURCES: Sources such as Medline (through December 31, 2014), Embase (through December 31, 2014), Wiley Online Library (through December 31, 2014), and the Cochrane Library (through December 31, 2014) were searched. STUDY SELECTION: Data of randomized and non-randomized clinical trials related to MIO versus OE were included. INTERVENTIONS: Eligible studies were those that reported patients who underwent MIO procedure. The control group included patients undergoing conventional OE. STUDY APPRAISAL AND SYNTHESIS METHODS: Fixed or random -effects models were used to calculate summary odds ratios (ORs) or relative risks (RRs) for quantification of associations. Heterogeneity among studies was evaluated by using Cochran's Q and I2 statistics. RESULTS: A total of 48 studies involving 14,311 cases of resectable oesophageal cancer were included in the meta-analysis. Compared to patients undergoing OE, patients undergoing MIO had statistically reduced occurrence of IHM (OR=0.69, 95%CI =0.55 -0.86). Patients undergoing MIO also had significantly reduced incidence of pulmonary complications (PCs) (RR=0.73, 95%CI = 0.63-0.86), pulmonary embolism (PE) (OR=0.71, 95%CI= 0.51-0.99) and arrhythmia (OR=0.79, 95%CI = 0.68-0.92). Non-significant reductions were observed among the included studies in the occurrence of anastomotic leak (AL) (OR=0.93, 95%CI =0.78-1.11), or Gastric Tip Necrosis (GTN) (OR=0.89, 95%CI =0.54-1.49). LIMITATION: Most of the included studies were non-randomized case-control studies, with a diversity of study designs, demographics of participants and surgical intervention. CONCLUSIONS: Minimally invasive oesophagectomy (MIO) has superiority over open oesophagectomy (OE) in terms of the occurrence of in-hospital mortality (IHM) and should be the first-choice surgical procedure in esophageal surgery.

Multivariate statistical analysis of clinicopathologic factors influencing survival of patients with bile duct carcinoma.

AIM: To evaluate the influence of various clinicopathologic factors on survival of patients with bile duct carcinoma after curative resection. METHODS: A retrospective analysis was made for 86 cases of bile duct carcinoma treated from January 1981 to September 1995. Fifteen clinicopathologic factors possibly influencing survival were selected. Independent variables were first analyzed by univariate methods. Survival for variable was estimated by the method of Kaplan and Meier. The variables that were statistically significant by univariate analysis were included in a multivariate analysis, which were confirmed using the Cox stepwise proportion hazard model with the help of SPSS 10.0 for Windows software. RESULTS: The overall cumulative survival rate was 72.6 % at 1 year, 32.4 % at 3 years, and 18.7 % at 5 years. The results of univariate analysis showed that the major significant prognostic factors influencing survival of these patients were histological type of lesion, lymph node metastasis, pancreatic invasion, duodenal invasion, perineural invasion, macroscopic vessel involvement, resected surgical margin and depth of cancer invasion (P=0.02, 0.02, 0.004, 0.005, 0.01, 0.43, 0.03 and 0.04). Age, sex, location of tumor, size of tumor, macroscopic type of lesions, hepatic metastasis, and hepatic invasion were not significantly associated with prognosis (P>0.05). Pancreatic invasion, perineural invasion and lymph node metastases were the three most important prognostic factors by multivariate analysis using the Cox proportional hazards model. CONCLUSION: Pancreatic invasion, perineural invasion and lymph node metastases are the most important prognostic factors for bile duct carcinoma after curative resection.

Multivariate analysis by Cox Proportional Hazards Model on prognoses of patients with bile duct carcinoma after resection.

OBJECTIVE: To evaluate the influence of various clinicopathologic factors on the survival of patients with bile duct carcinoma after curative resection. METHODS: A retrospective analysis was performed on 86 cases of bile duct carcinoma treated from January 1981 to September 1995. Fifteen clinicopathologic factors that could possibly influence survival were selected. A multivariate analysis of these individuals was performed using the Cox Proportional Hazards Model. RESULTS: The overall cumulative survival rate was 73% for 1 year, 32% for 3 years and 19% for 5 years. The results of univariate analysis showed that the major significant prognostic factors for influencing survival of these patients were type of histological lesion, lymph node metastasis, pancreatic invasion, duodenal invasion, perineural invasion, macroscopic vessel involvement, resected surgical margin and depth of cancer invasion (P < 0.05). Pancreatic invasion, perineural invasion and lymph node metastases were the three most important prognostic factors determined by multivariate analysis using the Cox Proportional Hazards Model. CONCLUSION: Pancreatic invasion, perineural invasion and lymph node metastases are the most important prognostic factors for bile duct carcinoma after curative resection.

Association between irrigation fluids, washout volumes and risk of local recurrence of anterior resection for rectal cancer: a meta-analysis of 427 cases and 492 controls.

BACKGROUND: Rectal washout can prevent local recurrence after anterior resection of rectal cancer. Few studies have focused particularly on the association between irrigation fluids volume or agents and the risk of local recurrence after anterior resection of rectal cancer. OBJECTIVE: To estimate the association between irrigation fluids types, volumes of rectal washout and risk of local recurrence after anterior resection for cancer. DATA SOURCES: Relevant studies were identified by a search of Medline, Embase, Wiley Online Library, China National Knowledge Infrastructure, Cochrane Oral Health Group Specialized Register, Wanfang databases and Google Website from their inception until October 18,2013. STUDY SELECTION: Studies reporting the association between rectal washout types and volumes and risk of local recurrence after anterior resection for cancer were included. INTERVENTIONS: Eligible studies used rectal washout. Control groups were defined as no washout. STUDY APPRAISAL AND SYNTHESIS METHODS: Random-effects model were used to obtain summary estimates of RR and 95% CI, with Stata version 11 and RevMan 5.2.5 softwares used. The quality of report was appraised in reference to the MINORS item. RESULTS: Of the 919 rectal cancer patients in 8 included studies, a total of 61(6.64%) cases of local recurrence were reported, with a pooled RR 0.51 (95%CI = 0.28-0.92, P = 0.03). The RRs 0.37 and 0.39 in normal saline and washout volume (≥ 1500 ml normal saline) subgroup, respectively, indicated that rectal washout with normal saline, or ≥ 1500 ml in volume could significantly reduce local recurrence (LR) rate (95% CI = 0.17-0.79, P = 0.01; 95% CI = 0.18-0.87, P = 0.02) after anterior resection for cancer. LIMITATION: The included studies were non-randomized observational studies, with diversity of study designs. CONCLUSION: Rectal washout with normal saline alone can reduce the risk of local recurrence in patients with resectable rectal cancer, and 1.5 liters rectal washout in volume is recommended.

[Geldanamycin inhibits proliferation and motility of human HER2/neu-overexpressing breast cancer cell line SKBr3].

OBJECTIVE: To investigate the antitumor effect of a benzoquinone ansamycin antibiotic, geldanamycin (GA), against HER2 /neu tyrosine kinase-overexpressing human breast cancer cell line SKBr3. METHODS: To evaluate the antitumor activity of GA, the degradation of HER2 /neu tyrosine kinase in GA-treated SKBr3 cells was analyzed by Western blotting, their proliferation assessed using MTT assay, and the cell cycle distribution identified by flow cytometry. RT-PCR and Real-time PCR were employed to detect cyclin D1 mRNA expression and cell culture inserts model was used to evaluate the motility of the cells. RESULTS: GA induced a dose- and time-dependent degradation of HER2 /neu tyrosine kinase and cell proliferation inhibition. GA treatment obviously decreased the survival rates of the cancer cells, leading also to a dose-dependent G(1) arrest. The antitumor effects of GA proved to be relevant with declined transcription of cyclin D1. The GA-treated cells also exhibited reduced motility. CONCLUSION: GA can efficiently destabilize HER2 /neu tyrosine kinase and inhibit the proliferation and motility of human breast cancer cell line SKBr3 overexpressing HER2 /neu tyrosine kinase.

Factors influencing the prevalence of gallstones in liver cirrhosis.

BACKGROUND AND AIMS: To investigate the prevalence of gallstone disease in Chinese patients with liver cirrhosis and to identify risk factors for cholelithiasis. METHODS: Blood samples were tested and ultrasonographic examination of the upper abdomen was conducted to observe the prevalence of gallstones in 90 compensated cirrhotic patients (Child-Pugh A), 180 decompensated cirrhotic patients (Child-Pugh B, C) and 300 controls. Risk factors for gallstone formation (age, sex, pregnancy, family history) and the characteristics of liver cirrhosis (Child class, inside diameter of portal vein), and gallbladder (wall thickness) were assessed. RESULTS: Gallstones were found more often in cirrhotic patients (23.7%) than in controls (7.33%, P < 0.001). The prevalence of gallstones in decompensated cirrhotic patients was higher than that of the compensated cirrhotic patients (P < 0.001). Advanced age, female sex, family history of gallstones, gallbladder wall thickness 4 mm or greater and inside diameter of portal vein 13 mm or greater were significantly associated with gallstone disease in patients with liver cirrhosis. Multivariate analysis revealed that age (P < 0.001), sex (P = 0.0005) and thickness (4 mm or greater) of the gallbladder wall (P = 0.0064) were independently associated with gallstone disease in such patients. CONCLUSIONS: This study confirms the high prevalence of cholelithiasis in liver cirrhosis. Age and sex are risk factors for gallstones and gallbladder wall thickness could be an additional risk factor for the development of gallstone in patients with liver cirrhosis.