Frequence,Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors

Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted.     

Renal function and morphology in Sudanese patients with advanced hepatosplenic schistosomiasis and portal hypertension

The association between glomerular disease and hepatosplenic schistosomiasis is well documented in reports from South America. During the present hospital investigation in Sudan, 58 patients admitted for intercurrent complications of advanced hepatosplenic schistosomiasis were studied. The patients, median age 35 years, had no concurrent Schistosoma haematobium infection. Diagnostic criteria included an enlarged spleen (n = 58), at least 1 episode of hematemesis (n = 55) and/or melena (n = 36), endoscopical demonstration of gastroesophageal varices (29/29 studied), ultrasonographical imaging of hepatic periportal fibrosis (18/18 studied), and intraoperative liver biopsy with characteristic histological findings (11/16 biopsied). Serum creatinine, urea, electrolytes, cholesterol, total protein, and electrophoresis were within normal limits. Median urinary protein/creatinine ratio was 0.06 and thereby not significantly different from European reference values. Only 1 patient had proteinuria of 1.7 g/l. Minimal hematuria was found in 5 patients. Ten kidney biopsies were taken intraoperatively during a portal decompression procedure (Hassab operation). Light, immunofluorescence, and electron microscopy produced no evidence of glomerulonephritis. These findings indicate that S. mansoni induced nephrotic syndrome may be less frequent in Sudan than in South America. Renal involvement due to S. mansoni infection may therefore encompass geographical variances.     

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study

Background:

Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer.

Methods:

By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982–2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer.

Results:

Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81–0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99–1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15–1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01–1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers.

Conclusions:

Overall, HZ was not a predictor of increased mortality following subsequent cancer.     

Effect of peripheral endothelin‐1 concentration on carcinoma‐induced pain in mice

In this study, we investigated the role of the peripheral endothelin‐1 (ET‐1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET‐1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET‐1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET‐1 within the cancer microenvironment was significantly greater in the SCC group. Intra‐tumor expression of both ET‐1 mRNA and ET‐1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET‐1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET‐1 receptor antagonism show promise and may be tumor type specific.