Phase II Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma

A trial of melphalan and methyl-gag was undertaken in 16 patients with metastatic renal cell carcinoma. Among 14 evaluable patients, 6 had stabilization of disease. No significant responses were observed. While both drugs have produced occasional responses in renal cancer, their combination shows no therapeutic advantage.     

Management of hydatid disease of the liver—10 years'' experience in a non-endemic area

The incidence of hydatid disease of the liver caused byEchinococcus granulosus in Austria, a nonendemic region in central Europe, is documented over a 10-year period. Since 1984, 28 patients (24 women, 4 men) with hydatid disease of the liver have undergone surgery in our department. A definitive diagnosis was established by combining serological tests (an enzyme-linked immunosorbent assay withEchinococcus multilocularis antigen and an indirect hemagglutination assay withEchinococcus granulosus antigen) and abdominal imaging (computed tomography scan and ultrasonography). Twenty-four patients (85.7%) had uncomplicated echinococcosis; in most of them (16) total closed pericystectomy was done. Four patients (14.3%) had complicated echinococcosis, suffering from intrabiliary rupture and spontaneous perforation into the peritoneal cavity, and in two of these patients (7.1%) pyogenic transformation, one with abscess perforation, occurred. Postoperative complications were significantly more common in patients with complicated echinococcosis and included two bile leaks (necessitating prolonged tube drainage), pleural effusion, atelectasis, and wound infection. One recurrence of hydatid infection due to previous spontaneous perforation required reoperation 4 years after the primary event. The low recurrence rate of uncomplicated echinococcosis (0%) over a mean period of 5.6 years and of 3.6% when peritoneal echinococcosis was included may be the result of the radical surgical technique employed.     

Defining the role of TORC1/2 in multiple myeloma

Mammalian target of rapamycin (mTOR) is a downstream serine/threonine kinase of the PI3K/Akt pathway that integrates signals from the tumor microenvironment to regulate multiple cellular processes. Rapamycin and its analogs have not shown significant activity in multiple myeloma (MM), likely because of the lack of inhibition of TORC2. In the present study, we investigated the baseline activity of the PI3K/Akt/mTOR pathway TORC1/2 in MM cell lines with different genetic abnormalities. TORC1/2 knock-down led to significant inhibition of the proliferation of MM cells, even in the presence of BM stromal cells. We also tested INK128, a dual TORC1/2 inhibitor, as a new therapeutic agent against these MM cell lines. We showed that dual TORC1/2 inhibition is much more active than TORC1 inhibition alone (rapamycin), even in the presence of cytokines or stromal cells. In vitro and in vivo studies showed that p-4EBP1 and p-Akt inhibition could be predictive markers of TORC2 inhibition in MM cell lines. Dual TORC1/2 inhibition showed better inhibition of adhesion to BM microenvironmental cells and inhibition of homing in vivo. These studies form the basis for further clinical testing of TORC1/2 inhibitors in MM.     

Fucoxanthin alters the apelin-13/APJ pathway in certain organs of γ-irradiated mice

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg^–1 day^–1, i.p) and exposed to γ-radiation (2.5 Gy week^–1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues’ architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.     

Endoskopische Palliation der malignen Magenausgangsstenose durch selbstexpandierbare Metallstents

INTRODUCTION: Malignant gastric outlet stenosis is caused by tumour obstruction and restricts the oral intake of food, resulting in a seriously reduced quality of life. Endoscopic implantation of self expanding metal stents (SEMS) can clear stenosis in the GI-tract and reestablish and preserve the passage in the GI-tract. PATIENTS AND METHODS: Between October 2001 and April 2003 seven patients with malignant gastric outlet stenosis have been treated by the implantation of SEMS. Four patients had malignant stenosis in the upper duodenum or gastric antrum, two patients had stenosis because of tumour recurrence in the efferent loop of the jejunum after gastric resection because of gastric carcinoma and one patient had an obstruction 20 cm distal of the oesophagus after gastrectomy because of gastric cancer. RESULTS: In all patients obstruction was cleared by the implantation of SEMS, and oral intake of food was possible in all patients after two days. No serious complications occurred during or after stent implantation. CONCLUSION: Stent implantation for the treatment of malignant gastric outlet stenosis is a cost effective procedure, associated with low risk and low stress for the patient, and provides excellent palliation of symptoms in patients with malignant gastric outlet stenosis.     

Primary biliary cystadenocarcinoma perforating the duodenum and left intrahepatic biliary tree -mimicking a hydatid cyst

Abstract: We report the case of a 76-year-old woman with biliary cystadenocarcinoma perforating the left biliary tree and exhibiting intra-tumoral gas bubbles resulting from invasion of the duodenum. The clinical history included subfebrile temperatures of 3 months duration, and pains associated with an abdominal mass in the right upper quadrant. Blood tests showed leucocytosis, and radiological studies revealed the features of a partially calcified septated tumor with nodular components combined with multiple gas-fluid levels, mimicking an infected hydatid cyst. Intraoperative ultrasonography, cholangiography and frozen section histology were necessary to prove the malignant nature of this cystic tumor. Provided that complete resection with strict adherence to oncological precepts is possible, the prognosis of cystadenocarcinoma is better than in hepatocellular or cholangiocellular carcinoma.