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- Isolated pancreatic metastasis from malignant melanoma: is pancreatectomy worthwile? [Journal Article]
- J Surg Tech Case Rep 2013 Jul; 5(2):82-4.
Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be efficient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here the case of an IPMMM patient successfully treated by pancreaticoduodenectomy with a prolonged survival of 6 years.
- Pancreatitis in scrub typhus. [Journal Article]
- J Glob Infect Dis 2014 Jan; 6(1):28-30.
Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.
- Excess exposure to insulin (glargine) induces type 2 diabetes mellitus in mice on chow diet. [JOURNAL ARTICLE]
- J Endocrinol 2014 Apr 16.
We have previously shown that insulin plays an essential role in nutrients-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical T2DM in normal mice on chow diet. C57BL/6 mice were treated with long-acting insulin (glargine) once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and mitochondrial content of cholesterol in tissues. Mitochondrial content of cholesterol and its association with oxidative stress in cultured hepatocytes and beta cells were also examined. Results show that chronic exposure to insulin caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess insulin led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased mitochondrial content of cholesterol in liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce T2DM in normal mice on chow diet.
- Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-Octreotide for localisation of clinically and biochemically suspected insulinoma. [JOURNAL ARTICLE]
- Q J Nucl Med Mol Imaging 2014 Apr 17.
Localisation of primary tumor in insulinoma is often difficult. We evaluated the role of 68Ga-DOTA-Nal3-Octreotide (DOTANOC) PET/CT for localisation of primary tumor in patients with clinical and biochemical suspicion of insulinoma.Data of 35 patients (Age: 38.4±16.5 years) who underwent 68Ga-DOTANOC PET/CT for clinical and biochemical suspicion of insulinoma (hypoglycemia, raised serum insulin and C-peptide levels) were retrospectively analyzed. PET/CT images were evaluated visually and semiquantitatively (SUV) by two experienced nuclear medicine physicians. A definite lesion in pancreas on non contrast CT showing increased 68Ga-DOTANOC was taken as positive. In the absence of CT lesion focal 68Ga-DOTANOC uptake in the pancreas more than liver was taken as positive. All patients had also undergone conventional imaging (CIM) [CT/MRI/endosonography] and their reports were retrieved for comparison. Histopathology and/or imaging/clinical/biochemical follow up (minimum 6 months) was used as reference standard.The mean serum insulin levels was 51.6±54 μIU/ml and C-peptide level was 6.9±7.3 ng/ml. 68Ga-DOTANOC-PET/CT was interpreted as positive in 11 patients (31.5%) and negative in 24 (68.5%). PET/CT demonstrated total 16 pancreatic lesions in 11 patients. In two patients it also showed both liver and lymph nodal metastases. 68Ga-DOTANOC PET/CT was true positive in 8, true negative in 1, false positive in 3 and false negative in 23 patients. Per patient based sensitivity of PET/CT was 25.8% (95% CI: 11.844.6), specificity was 25% (95% CI: 0.680.5) and accuracy was 25.7%. The mean SUVmax of pancreatic lesions was 13.8±11.1. On comparison no significant difference was seen between CIM and PET/CT on patient based (P=1.00) or lesion based comparison (P=0.790).68Ga-DOTANOC PET/CT has limited utility for localising the primary tumor in patients with clinical and biochemical suspicion of insulinoma. However, it might be useful for differentiating benign and malignant insulinoma. Further prospective comparative studies are warranted.
- Histomorphological features of pancreas and liver in chronic alcoholics - an analytical study in 390 autopsy cases. [Journal Article]
- Indian J Pathol Microbiol 2014 Jan-Mar; 57(1):2-8.
Introduction: Chronic pancreatitis and liver disease are two conditions that commonly co-exist in chronic alcoholics with variable incidences.
Aim:To evaluate frequency pancreatitis in patients with a history of chronic alcohol abuse. Materials and
Methods:A total of 390 autopsies over 11 year's period were included in the study. Gross and microscopic assessment of liver and pancreas were performed. Available clinical and laboratory parameters were recorded.
Results:Age ranged from 22 to 65 years with a mean age of 45.32 years. All 390 consecutive patients included in the study were males. Majority of the patients had primarily presented with alcohol related liver diseases whereas few had presented with features of pancreatitis. Micronodular cirrhosis was present in 292 cases. Features of chronic pancreatitis were observed in 42 cases and 8 of these cases had associated changes of acute hemorrhagic pancreatitis. Prevalence of pancreatitis was more in cirrhotics as compared to non-cirrhotics, and acute pancreatitis was mostly seen in non-cirrhotics. Dominant pattern of fibrosis was perilobular followed by periductal, intralobular and diffuse.
Conclusion:Chronic pancreatitis as evidence by the presence of parenchymal fibrosis was more frequently observed in alcoholic cirrhosis cases than that in non-cirrhotic alcoholic liver disease, thereby suggesting common underlying pathobiology in the development of fibrosis in liver as well as in pancreas.
- Impact of Fructose Diet and Renal Failure on the Function of Pancreatic Islets. [JOURNAL ARTICLE]
- Pancreas 2014 Apr 14.
This study was designed to evaluate the impact of fructose-rich diet and chronic kidney disease (CKD) on the in vitro function of pancreatic islets.Fifty-four rats were divided into 3 equal groups as follows: control, rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6 that underwent uninephrectomy and kidney cortex mass resection. Each group was further assigned to 3 diet protocols-regular diet, regular diet with 10% fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin administration, C-peptide, glycated hemoglobin level, serum urea nitrogen, creatinine clearance, and homeostasis model assessment of insulin resistance were evaluated. Static glucose insulin stimulation test of isolated pancreatic islets and histologic analysis of pancreatic tissue were performed.The F10 diet increased the levels of insulin and C-peptide in all groups. Homeostasis model assessment of insulin resistance was increased in all animals fed with fructose. The elevated levels of creatinine and diminished creatinine clearance were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet resulted in high levels of serum insulin and C-peptide and glucose-stimulated insulin secretion. Fructose-rich diet increased the islet size and number, with irregular morphology and exocrine tissue fibrosis.The fructose-rich diet accelerates the progression of CKD and affects the pancreatic islet function.
- Transcriptional dissection of pancreatic tumors engrafted in mice. [JOURNAL ARTICLE]
- Genome Med 2014 Apr 16; 6(4):27.
Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient-derived xenograft (PDX) models is a promising platform for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine tumor environment on the gene expression of the engrafted human tumoral cells.We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data of 18 PDX models, 53 primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC system were further compared with public available microarray data from 42 PDX models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC). We developed a robust analysis protocol to explore the gene expression space. In addition, we completed the analysis with a functional characterization of PDX models, including if changes were caused by murine environment or by serial passing.Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based on their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models can be separated into two different groups that share some partial similarity with their corresponding original primary tumors. Our results point to the lack of human stromal involvement in PDXs as a major factor contributing to their differences with the original primary tumors. The main functional differences between pancreatic PDX models and human PDAC are the lower expression of genes involved in pathways related to extracellular matrix and hemostasis and the up regulation of cell cycle genes. Importantly, most of these differences are detected in the first passages after the tumor engraftment.Our results suggest that PDX models of PDAC and HCC retain, to some extent, a gene expression memory of the original primary tumors, while this pattern is not detected in conventional cancer cell lines. Expression changes in PDXs are mainly related to pathways reflecting the lack of human infiltrating cells and the adaptation to a new environment. We also provide evidence of the stability of gene expression patterns over subsequent passages, indicating early phases of the adaptation process.
- Systemic effects induced by intralesional injection of omega-conotoxin MVIIC after spinal cord injury in rats. [JOURNAL ARTICLE]
- J Venom Anim Toxins Incl Trop Dis 2014 Apr 16; 20(1):15.
Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol.These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue.
- Agreement of serum feline pancreas-specific lipase and colorimetric lipase assays with pancreatic ultrasonographic findings in cats with suspicion of pancreatitis: 161 cases (2008-2012). [Journal Article]
- J Am Vet Med Assoc 2014 May 1; 244(9):1060-5.
Objective-To investigate agreement of a feline pancreas-specific lipase assay and a colorimetric lipase assay with a 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) substrate with results of pancreatic ultrasonography in cats with suspicion of pancreatitis. Design-Retrospective case series. Animals-161 client-owned cats with suspicion of pancreatitis. Procedures-Feline pancreas-specific lipase concentration and DGGR lipase activity were measured from the same blood sample in cats undergoing investigation for pancreatitis, with < 24 hours between ultrasonography and lipase determinations. Ultrasonographic variables evaluated were ultrasonographic diagnosis of pancreatitis, enlargement, margins, echogenicity, mesenteric echogenicity, peripancreatic free fluid, cysts, masses, and common bile and pancreatic duct dilation. Agreement was assessed by use of the Cohen κ coefficient. Results-Agreement between the lipase assays was substantial (κ = 0.703). An ultrasonographic diagnosis of pancreatitis had fair agreement with feline pancreas-specific lipase concentration > 5.4 μg/L (κ = 0.264) and DGGR lipase activity > 26 U/L (κ = 0.221). The greatest agreement between feline pancreas-specific lipase concentration > 5.4 μg/L and DGGR lipase activity > 26 U/L was found for a hypoechoic and mixed-echoic (κ = 0.270 and 0.266, respectively), hypoechoic (κ = 0.261 and 0.181, respectively), and enlarged (κ = 0.218 and 0.223, respectively) pancreas. Conclusions and Clinical Relevance-Agreement between pancreatic ultrasonography and lipase assay results was only fair. It remains unknown whether lipase results or pancreatic ultrasonography constitutes the more accurate test for diagnosing pancreatitis; therefore, results of both tests need to be interpreted with caution.
- The protective effects of shen-fu injection on experimental acute pancreatitis in a rat model. [Journal Article]
- Oxid Med Cell Longev 2014.:248786.