Mitochondrial neurogastrointestinal encephalomyopathy imitating Crohn's disease: a rare cause of malnutrition.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by a mutation in the TYMP gene encoding thymidine phosphorylase. MNGIE causes gastrointestinal and neurological symptoms in homozygous individuals and is often misdiagnosed as anorexia nervosa, inflammatory bowel disease, or celiac disease. We present the case of a 26-year-old female with MNGIE, who was initially diagnosed with anorexia nervosa and Crohn's disease. The diagnosis of MNGIE was established by biochemical confirmation of elevated serum and urine thymidine and deoxyuridine levels after multiple examinations and several years of disease progression and ineffective treatment. Subsequent molecular genetic testing demonstrated a homozygous TYMP gene mutation. MNGIE should be considered in patients with unexplained malnutrition, intestinal dysmotility, and atypical neurological symptoms.

Mucinous Cystic Neoplasm of the Liver or Intraductal Papillary Mucinous Neoplasm of the Bile Duct? A Case Report and a Review of Literature.

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.

Dysregulation of KRAS signaling in pancreatic cancer is not associated with KRAS mutations and outcome.

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, and no targeted therapy is currently available. The aim of the present study was to investigate the prognostic significance of the expression of V-Ki-ras2 Κirsten rat sarcoma viral oncogene homolog (KRAS), downstream signaling pathway genes and the association with clinical characteristics in PDAC patients undergoing radical surgery. Tumors and adjacent non-neoplastic pancreatic tissues were examined in 45 patients with histologically verified PDAC. KRAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene mutation analysis was performed using the KRAS/BRAF/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α array. The transcript profile of 52 KRAS downstream signaling pathway genes was assessed using quantitative-polymerase chain reaction. KRAS mutation was detected in 80% of cases. The genes of four signaling pathways downstream of KRAS, including the phosphoinositide 3-kinase/3-phosphoinositide-dependent protein kinase 1/V-akt murine thymoma viral oncogene homolog 1, RAL guanine nucleotide exchange factor, Ras and Rab interactor 1/ABL proto-oncogene-1, non-receptor tyrosine kinase, and RAF proto-oncogene serine/threonine-protein kinase/mitogen-activated protein kinase pathways, exhibited differential expression in PDAC compared with that in the adjacent normal tissues. However, no significant differences in expression were evident between patients with KRAS-mutated and wild-type tumors. The expression of KRAS downstream signaling pathways genes did not correlate with angioinvasion, perineural invasion, grade or presence of lymph node metastasis. Additionally, the presence of KRAS mutations was not associated with overall survival. Among the KRAS downstream effective signaling pathways molecules investigated, only v-raf-1 murine leukemia viral oncogene homolog 1 expression was predictive of prognosis. Overall, KRAS mutation is present in the majority of cases of PDAC, but is not associated with changes in the expression of KRAS downstream signaling pathways and the clinical outcome. This may partly explain the failure of KRAS-targeted therapies in PDAC.

MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive malignancy with late presentation, metastatic potential and very poor prognosis. Therefore, there is an urgent need for novel diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Altered expression of microRNAs has been reported in wide range of malignancies, including pancreatic ductal adenocarcinoma. The aim of this study was to analyze the expression of selected microRNAs in normal pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma tissues and evaluate their diagnostic and prognostic potential. FINDINGS: Using quantitative real-time PCR, expression levels of 4 microRNAs were examined in 74 tumor tissues, 18 tissues of chronic pancreatitis and 9 adjacent normal tissues and correlated with clinicopathological features of patients. Expression levels of miR-21, miR-34a and miR-198 were significantly higher, whereas levels of miR-217 were significantly lower in pancreatic ductal adenocarcinomas compared to healthy tissues and tissues of chronic pancreatitis. Moreover, increased expression of miR-21 and miR-198 was significantly associated with shorter disease free survival and overall survival. CONCLUSIONS: Our data suggest that altered expression of examined microRNAs is related to neoplastic transformation and progression of the disease and these microRNAs could serve as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373952531543898.

The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer.

OBJECTIVES: The aim of this study was to investigate the prognostic significance of fourteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. METHODS: Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and confirmed by sequencing. RESULTS: SLC22A3 and SLC22A18 were upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC28A1 was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Protein expression of SLC22A1, SLC22A3 and SLC29A3 in tumor tissues of patients with pancreatic carcinoma was observed by immunoblotting for the first time. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. CONCLUSIONS: This study identified a number of associations of transcript levels of SLCs with prognosis of pancreatic cancer patients.