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Abstract Background Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. Methods A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. Results ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. Conclusion ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs.

A pregnant woman with extensive brain lesions on magnetic resonance imaging was tested positive for anti-aquaporin4 (AQP4) antibodies. An open biopsy of the left temporal lobe showed pathological changes in both the white and gray matter. Hematoxylin and eosin, Klüver–Barrera, and myelin basic protein staining results were indicative of demyelination in the white matter. Loss of AQP4 and glial fibrillary acidic protein was observed in the white matter, and this finding is consistent with the neuropathological findings of neuromyelitis optica spinal lesions. Moreover, loss of AQP4 was observed in the gray matter. The presence of anti-AQP4 antibodies, and the pathology, led to the diagnosis of anti-AQP4 antibodies-related encephalopathy. [ABSTRACT FROM AUTHOR]

A pregnant woman with extensive brain lesions on magnetic resonance imaging was tested positive for anti-aquaporin4 (AQP4) antibodies. An open biopsy of the left temporal lobe showed pathological changes in both the white and gray matter. Hematoxylin and eosin, Klüver-Barrera, and myelin basic protein staining results were indicative of demyelination in the white matter. Loss of AQP4 and glial fibrillary acidic protein was observed in the white matter, and this finding is consistent with the neuropathological findings of neuromyelitis optica spinal lesions. Moreover, loss of AQP4 was observed in the gray matter. The presence of anti-AQP4 antibodies, and the pathology, led to the diagnosis of anti-AQP4 antibodies-related encephalopathy.

The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method for HLA class I APM expression showing different expression patterns among cell lines was performed for 95 surgical specimens from patients with esophageal cancer. Prognostic factors were the down-regulation of HLA-HC, and the up-regulation of β2 microglobulin and TAP-1 in the cancer tissues. Multivariate analysis using a Cox regression model indicated that the down-regulation of HLA-HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145, respectively). Although there was no significant difference in survival for selected p-stage I and II patients (n=54) in all APM components, only down-regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression model for selected p-stage III and IV patients (n=41). In conclusion, the current results suggest that the down-regulation of HLA-HC in tumors is especially associated with a poor prognosis among advanced esophageal cancer patients.

A 45-year-old man was admitted to our hospital with flaccid paraplegia. Neurological examination at a local hospital, 2 months before admission to our hospital, showed sensory impairment of the right posterior surface of the thigh and a decreased Achilles tendon reflex. Spinal magnetic resonance imaging (MRI) showed a T₂ weighted high-intensity area at the Th10-11 level that was more pronounced in the gray matter. The patient developed flaccid paraparesis and urinary retention. No improvement was observed after 2 rounds of methylprednisolone (mPSL) pulse therapy. Spinal cord biopsy showed demyelinated axons and myelinophagia without any tumorous lesion. Myelopathy exacerbated, and hence, plasma exchange was performed. However, this was ineffective. We suspected that myelopathy was caused by intravascular lymphoma (IVL) because of the presence of a low-grade fever, weight loss, and elevated serum soluble IL-2 receptor titers. Random biopsies, including skin, rectal, bone marrow, muscle, and renal biopsies, and splenectomy were performed to make a definite diagnosis of IVL myelopathy. Among these biopsies, the diagnosis of IVL myelopathy was confirmed from the renal specimen. The patient underwent chemotherapy at our hospital, and the IVL remitted. The results of this study confirm that sufficient systemic investigation by using tissue biopsy specimens should be performed in order to confirm the diagnosis of IVL myelopathy.

Cholangiocarcinoma is an intractable cancer for which there is no effective therapy other than surgical resection, and many patients are not candidates for this treatment. Even for patients who undergo surgical resection, the 5-year survival rate is low. One reason for this is that the disease is often detected in late stages. Thus, there is a clear need for better biomarkers to facilitate early diagnosis and prognostication. During the biomarker discovery phase of our study, we used LC-MS-based proteomics with spectral counting, a semiquantitative approach to differential expression profiling, in paired cancerous and normal bile duct tissue samples from two cases. In total, 38 proteins up-regulated in the cancer samples were identified. These were verified using a SILAC method for MS-based validation. The results led to the identification of well-characterized proteins and proteins of unknown function that are up-regulated in cholangiocarcinoma. We used immunoblot analysis to validate four candidate biomarkers, actinin-1, actinin-4, protein DJ-1 and cathepsin B, with the test case samples and four additional cholangiocarcinoma case samples. Each of the four candidate proteins was overexpressed in a subset of five of the six cases tested. By immunohistochemistry, we further confirmed that expression of these proteins was elevated in cancer cells as compared with normal bile duct cells. Thus, we successfully identified several proteins up-regulated in cholangiocarcinoma. These proteins are candidate biomarkers and may also help to provide new insights into our understanding of the disease.