Long-term outcome of patients with advanced pancreatic cancer treated with sequential chemotherapies before the era of modern combination therapy protocols.

INTRODUCTION: Patients (pts) with locally advanced (LAPC) or metastatic pancreatic ductal adenocarcinoma (mPDAC) have a dismal prognosis. Recently, new combination chemotherapies such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated superiority over gemcitabine monotherapy. However, a substantial proportion of pts cannot tolerate these intensive front-line protocols. Moreover, the long-term superiority of multiagent protocols over less intensive strategies remains to be shown. To provide a benchmark for future studies, we analyzed the outcome of patients with LAPC or mPDAC treated at the West German Cancer Center before the FOLFIRINOX/nab-paclitaxel + gemcitabine era. METHODS: This retrospective analysis included 201 consecutive pts with LAPC and mPDAC treated between 2007 and 2011. Efficacy parameters were correlated with type of chemotherapy, number of treatment lines and clinicopathological parameters. RESULTS: Gemcitabine monotherapy was given as first-line therapy in 51.1%, whereas 48.9% received combination chemotherapies such as gemcitabine/oxaliplatin or FOLFOX. Patients received a median of two lines of treatment, with 54.8% receiving second-line and 37.9% receiving third- and further-line therapies. There was no significant difference between gemcitabine monotherapy and combination therapies. Despite moderate activity of first-line treatment, median overall survival for LAPC was 11.3 months and 8.7 months for mPDAC. Multivariate analysis identified age and number of treatment lines as prognostic markers. CONCLUSION: The long-term outcome of unselected pts with LAPC and mPDAC treated before the introduction of aggressive multiagent chemotherapy protocols compares favorably with the results of contemporary benchmark trials. This suggests a multifactorial benefit from interdisciplinary care provided over sequential treatment lines at high volume expert centers.

Disproportionately elevated proinsulin levels in type 2 diabetic patients treated with sulfonylurea.

OBJECTIVE: Hyperproinsulinemia in type 2 diabetic subjects has recently been accepted as an independent cardiovascular risk factor. Moreover, it has been confirmed that high proinsulin concentrations stimulate amylin secretion by pancreatic beta-cells and amyloid accumulation within pancreatic islets leading to impairment of pancreatic islets secretory function. The association between sulfonylureas administration and secretory function of pancreatic beta-cells, especially concerning insulin precursor peptides, is not sufficiently elucidated. Preliminary studies by our research group revealed that the fasting proinsulin serum concentration is significantly higher in type 2 diabetic patients treated with sulfonylureas than in a well-matched group treated with insulin only. METHODS: A total of 101 subjects with type 2 diabetes were treated either with sulfonylureas (n = 32), with insulin (n = 40), with sulfonylureas + insulin (n = 17) or with diet alone (n = 12). RESULTS: The basal secretory function in the four groups were comparable (C-peptide fasting serum level > 0.5 ng/l). An effect of fasting glycemia, long-term metabolic control (HbA1c), postprandial hyperglycemia (1,5-anhydro-D-glucitol), insulin resistance (HOMA(IR)score) and diabetes duration on the fasting proinsulin serum level in the subjects treated could be excluded. CONCLUSION: The disproportionately high proinsulin levels are due to sulfonylureas therapy. The effect is independent of fasting glycemia, long-term metabolic control, postprandial hyperglycemia, diabetes duration and peripheral insulin resistance.

[Coxsackie B2 virus fatal meningoencephalitis in a student] / Meningoencefalite fatal por vírus coxsackie B2 em escolar.

OBJECTIVE: To present the case of a girl who was previously healthy but had fatal evolution due to Coxsackie B2 viral meningoencephalitis.METHODS: The authors describe the case of a female child with fatal meningoencephalitis caused by Coxsackie B2 virus and present a review of the literature (Medline and Lilacs).RESULTS: The girl was eight years old when she presented meningoencephalitis with bad evolution, leading to death on the 32nd day of internation. The exams showed positive serologic reaction to Coxsackie B2. The virus taken from two stool samples was isolated. The CRF exam showed an increase four times higher on Coxsackie B2 titulation.CONCLUSION: The death of healthy patients with enteroviral encephalitis, as described here, is rarely dealt with in the medical literature, perhaps because of lack of clinic suspicion. This case tries to drive attention to the importance of an early etiologic diagnosis in the meningoencephalities and the search for specific etiological treatment.

Rhodotorula glutinis fungemia: a case report and literatura review

A fatal case of Rhodotorula glutinis fungenia in an 11-year-old boy with acute lymphoblastc leukemia undergoing third reinduction chemotherapy is reported. This is the first case of fungemia by Rhodotorula glutinis reported in Brazil.