CK20 Positive Large-cell Neuroendocrine Carcinoma Presenting with Skin Metastases

We present a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma (LCNEC) presenting with multiple skin metastases as the primary manifestation. The patient was a 55-year-old man who presented with a one- month history of subcutaneous skin colored nodules of various sizes on his trunk. Pathologic examination of the skin revealed a nested and solid proliferation of large undifferentiated cells with vesicular nuclei and prominent nucleoli. Tumor cells were found to be immunohistochemically positive for CK 20, chromogranin A, synaptophysin, and CD56. Based on these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma with multiple skin metastases. Computed tomographic (CT) imaging found metastatic foci in the liver, pleura, bone, and lymph nodes. We were unable to identify the primary site of origin. To the best of our knowledge, this is the first case of a large cell neuroendocrine carcinoma with a primary manifestation of multiple skin metastases

Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

BACKGROUND: The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation. METHODS: Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells. RESULTS: Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC. CONCLUSION: The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis

Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer

Background: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum). Patients and methods This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. Results: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007). Conclusions: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer

Pulmonary Toxicity after a Quick Course of Combinatorial Vincristine, Bleomycin, and Cisplatin Neoadjuvant Chemotherapy in Cervical Cancer

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity

Clinical Application of Liver MR Imaging in Wilson's Disease

Objective: To determine whether there is a correlation between liver MR findings and the clinical manifestations and severity of liver dysfunction in patients with Wilson`s disease. Materials and Methods: Two radiologists retrospectively evaluated MR images of the liver in 50 patients with Wilson`s disease. The Institutional Review Board approved this retrospective study and informed consent was waived. MR images were evaluated with a focus on hepatic contour abnormalities and the presence of intrahepatic nodules. By using Fisher`s exact test, MR findings were compared with clinical presentations (neurological and non-neurological) and hepatic dysfunction, which was categorized by the Child-Pugh classification system (A, B and C). Follow-up MR images were available for 17 patients. Results: Contour abnormalities of the liver and intrahepatic nodules were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR finding showed a statistically significant difference (p < 0.05) among the three groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for splenomegaly (p = 0.243). The mean age of the patients with positive MR findings was higher than that of patients with negative MR findings. For patients with Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules, surface nodularity, and gallbladder fossa widening were more common. Intrahepatic nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n = 4, 24%) on follow-up MR images. Conclusion: MR imaging demonstrates the contour abnormalities and parenchymal nodules of the liver in more than half of the patients with Wilson`s disease, which correlates with the severity of hepatic dysfunction and clinical manifestations.Cope-Yokoyama S, 2010, WORLD J GASTROENTERO, V16, P1487, DOI 10.3748/wjg.v16.i12.1487Akhan O, 2009, EUR J RADIOL, V69, P147, DOI 10.1016/j.ejrad.2007.09.029Taly AB, 2007, MEDICINE, V86, P112, DOI 10.1097/MD.0b013e318045a00eMerle U, 2007, GUT, V56, P115, DOI 10.1136/gut.2005.087262Akpinar E, 2007, EUR J RADIOL, V61, P25, DOI 10.1016/j.ejrad.2006.11.006Kozic D, 2006, ACTA RADIOL, V47, P624, DOI 10.1080/02841850600702176Kim TJ, 2006, AM J NEURORADIOL, V27, P1373SEO JK, 2006, KOREAN J HEPATOL, V12, P333Panagiotakaki E, 2004, AM J MED GENET A, V131A, P168, DOI 10.1002/ajmg.a.30345Chu WCW, 2004, AM J ROENTGENOL, V183, P1339ALA A, 2004, CLIN LIVER DIS, V8, P787Gitlin JD, 2003, GASTROENTEROLOGY, V125, P1868, DOI 10.1053/S0016-5085(03)01512-9Ferenci P, 2003, LIVER INT, V23, P139Akhan O, 2002, EUR RADIOL, V12, pS66, DOI 10.1007/s00330-002-1589-6Awaya H, 2002, RADIOLOGY, V224, P769, DOI 10.1148/radiol.2243011495Ito K, 1999, RADIOLOGY, V211, P723Ko SF, 1998, ABDOM IMAGING, V23, P56MERGO PJ, 1994, RADIOGRAPHICS, V14, P1291BULL PC, 1993, NAT GENET, V5, P327TANZI RE, 1993, NAT GENET, V5, P344DAVIES SE, 1989, HISTOPATHOLOGY, V15, P385CANCADO EL, 1987, ARQ NEURO-PSIQUIAT, V45, P131CHILD CG, 1964, LIVER PORTAL HYPERTE, P50