Background/Aim: Methionine addiction, a fundamental and general hallmark of cancer, is due to the excess use of methionine for transmethylation, and is described as the Hoffman-effect. Methionine-addicted cancer cells can revert at low frequency to methionine independence when selected under methionine-restriction. We report here that highly-malignant methionine-addicted H460 human lung-cancer cells, when selected for methionine independence, have greatly-reduced tumorigenic potential. Materials and Methods: Methionine-addicted H460 parental cancer cells and methionine-independent revertant H460-R1 cells were injected in nude mice subcutaneously. Results: When the parental H460 methionine-addicted cells were injected in nude mice at 2.5×10⁵, 1×10⁵ and 5×10⁴, the cells could form tumors. In contrast, the H460-R1 methionine-independent revertant cells could not form tumors when the above-listed cell numbers were injected in nude mice. Conclusion: There is a tight linkage between methionine addiction and malignancy.

Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known. Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated. The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p < 0.01 for both DFS and OS). Infiltration of other types of immune cells did not correlate with survival. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable OS. High peritumoral MC infiltration predicts poor prognosis in patients who underwent hepatectomy for CRLM. The number of MCs in metastatic lesions is important for predicting the prognosis of CRLM patients and as an indication of therapy.

Endoscopic biliary stenting (EBS) is one of the most important palliative treatments for biliary tract cancer. However, reflux cholangitis arising from bacterial adherence to the inner wall of the stent must be avoided. We evaluated the use of EBS above the sphincter of Oddi to determine whether reflux cholangitis could be prevented in preoperative cases. Fifty-seven patients with primary biliary tract cancer were retrospectively recruited for the evaluation of stent placement either above (n = 25; inside stent group) or across (n = 32; conventional stent group) the sphincter of Oddi. We compared the stent patency periods prior to the time of surgical resection. The preoperative periods were 96.3 days in the conventional stent group and 96.8 days in the inside stent group (P = 0.979). Obstructive jaundice and/or acute cholangitis occurred in 7 patients (28.0%) in the inside stent group and in 15 patients (46.9%) in the conventional stent group during the preoperative period (P = 0.150). The average patency periods of the stents were 85.2 days (range, 13–387 days) for the inside stent group and 49.1 days (range, 9–136 days) for the conventional stent group (log-rank test: P = 0.009). The mean numbers of re-interventions because of stent occlusion were 0.32 for the inside stent group and 1.03 for the conventional stent group (P = 0.026). Post-endoscopic retrograde cholangiopancreatography complications occurred in 2 patients in the inside stent group and 4 patients in the conventional stent group (P = 0.516). Postoperative liver abscess occurred in 1 patient in the inside stent group and 5 patients in the conventional stent group (P = 0.968). Inside stent placement was the only significant preventative factor associated with stent obstruction based on univariate (hazard ratio [HR], 0.286; 95% confidence interval [CI], 0.114-0.719; P = 0.008) and multivariate (HR, 0.292; 95% CI, 0.114-0.750; P = 0.011) analyses. Temporary plastic stent placement above the sphincter of Oddi is a better bridging treatment than conventional stent placement in preoperative primary biliary tract cancer.