Endobiliary Radiofrequency Ablation for Malignant Biliary Obstruction over 32-Month Follow-Up.

Hilar cholangiocellular carcinoma (CCC) is a malignant neoplasm of epithelial origin occurring at the confluence of the right and left hepatic bile ducts. Typically, these tumors are small, poorly differentiated, exhibit aggressive biologic behavior with non-specific symptoms and tend to obstruct the intrahepatic bile ducts. Surgery is the only available curative option. Unfortunately, in less than half of the patients a complete resection is possible with poor survival rate in unresectable cases. In this report, we present the case of a 58-year-old woman with a history of unresectable hilar cholangiocarcinoma. Initially she was treated with intraductal dilatation of malignancy and placement of a plastic stent and chemotherapy (Gemcitabin® and Platinol®). Two years later she underwent a second-line chemotherapy with Gemcitabin® and Oxyplatin® because of tumor progression. Despite a second line chemotherapy and placement of an uncovered self-expandible metal stent (ucSEMS) that was extended later on by stent-in stent technique, there was tumor progression which led to a complex course with relapsing obstructive cholangiosepsis and cholestasis. Because of tumor ingrowth, endobiliary radiofrequency ablation of the malignant stenosis was performed in repeated sessions. This case illustrates that radiofrequency ablation of solitary malignant biliary obstruction is feasible, safe and allows an improvement of quality of life in non-operable patients.

Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned. PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR. RESULTS: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC. CONCLUSION: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.