Expression of secretory phospholipase A2s in human atherosclerosis development

Secretory phospholipase A2s (sPLA2s) contribute to the hydrolysis of phospholipid. Among them, sPLA2-IIA, -V, and -X have been regarded as enhancers of lipid accumulation in arterial intima. However, the distribution and production of the other types of sPLA2 in human aortic wall remain unclear. Therefore, in this study, the distribution and production of seven types of sPLA2 including IIA, IID, IIE, IIF, III, V, and X in atherosclerosis development in the human aorta were comprehensively examined by immunohistochemistry and in situ hybridization (ISH). The extent of sPLA2s expression increased with atherosclerosis development, but only sPLA2-IIF was never observed in the normal aorta. Double-immunostaining demonstrated that sPLA2-V expression was limited to smooth muscle cells (SMCs), although the other sPLA2s were expressed in both macrophages and SMCs. ISH using sPLA2 cDNAs revealed that the expression pattern of each mRNA was consistent with the results of immunohistochemistry for each corresponding sPLA2. These results indicate that the seven types of sPLA2 are expressed with various patterns in all stages of atherosclerosis development and may play an atherogenic role through degradation of phospholipid.     

Retroperitoneal Liposarcoma With Leiomyosarcomatous Differentiation

We herein describe a 60-year-old Japanese man with a giant retroperitoneal liposarcoma undergoing leiomyosarcomatous differentiation. He was admitted to our hospital because of a 5-month history of dysphagia and abdominal distention. Abdominal computed tomography showed a giant tumor that occupied the entire retroperitoneal space. The majority of the mass was lipomatous and low density; both a heterogenous and solid mass were also present. A giant retroperitoneal liposarcoma was diagnosed, and tumor resection was performed. At surgery, the tumor was mostly isolated from the retroperitoneum and other organs. Histopathologically, the tumor comprised well-differentiated and dedifferentiated liposarcoma with heterologous differentiation of the leiomyosarcomatous components, which is a rare phenomenon in liposarcoma. The patient was alive 3 years after the first treatment, although he has had 3 local recurrences (approximately one recurrence yearly) and has been treated by repeated resection and radiotherapy.Key words: Retroperitoneum, Liposarcoma, Leiomyosarcomatous differentiationDedifferentiated liposarcoma (DL) is one of the most frequent sarcomas of the retroperitoneum. It is defined by the association of an atypical lipomatous tumor, namely, areas of well-differentiated liposarcoma (WDL), with a dedifferentiated component. WDL is composed of mature adipocytes and atypical stromal cells with an enlarged, hyperchromatic nucleus. Usually, the dedifferentiated part of the liposarcoma is composed of either a spindle/pleomorphic high-grade sarcoma or a mixoid/spindle cell low-grade sarcoma. The WDL component may be easily overlooked, and DL may thus be mistaken for another high-grade sarcoma. It has been reported in one study that approximately 5% of the dedifferentiated component showed heterologous differentiation, such as leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, and angiosarcoma.¹ A less common phenomenon is the occurrence of WDL with leiomyosarcomatous (LMS) differentiation.² Limited to the retroperitoneum, only 8 cases of liposarcoma with LMS components have been reported.^3–7 We herein report a case of retroperitoneal liposarcoma comprising WDL and DL, with LMS components, treated by surgical resection.     

Central Bisegmentectomy for Malignant Liver Tumors: Experience in 8 Patients

Central bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. However, CBS has rarely been reported. Here, we investigate CBS in patients with suboptimal liver function for whom an extended lobectomy is not an optimal solution. Each case was 1 of 8 patients who underwent CBS for hepatocellular carcinoma (HCC) or colorectal cancer liver metastasis (CRLM) at the Department of Surgery, Jikei University Hospital. Indications for CBS consisted of CRLM in 3 patients and HCC in 5 patients. The median duration of operation was 552 minutes, and median blood loss was 2263 g. No postoperative nor in-hospital mortalities occurred. In this study, 1-, 2-, and 3-year disease-free survival rates were 62.5%, 12.5%, and 12.5%, respectively, and 1-, 2-, and 3-year overall survival rates were 100%, 100%, and 85.7%, respectively. CBS is advocated for central liver tumors in patients with suboptimal liver function for whom extended lobectomy could result in less than optimal remnant liver volume and function.Key words: Central bisegmentectomy, Colorectal cancer liver metastasis, Hepatocellular carcinomaCentral bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8.¹ McBride and Wallace² first reported this procedure in 1972. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. The traditional procedure for such tumors is extended right or left lobectomy or trisegmentectomy. Because of the possibility of conservation of remnant liver parenchymal volume, CBS may be superior to extended lobectomy or trisegmentectomy, especially for patients with low residual liver function due to viral hepatitis or adjuvant chemotherapy. However, CBS has rarely been reported. We herein report our experience with 8 patients who underwent CBS for colorectal cancer liver metastasis (CRLM) or hepatocellular carcinoma (HCC).     

Specific Expression of Apolipoprotein A-IV in the Follicle-Associated Epithelium of the Small Intestine

Background

Peyer’s patches (PPs), which are covered by specialized follicle-associated epithelium (FAE) including M cells, play a central role in immune induction in the gastrointestinal tract. This study is to investigate a new molecule to characterize PPs.

Methods

We generated a monoclonal antibody (mAb 10-15-3-3) that specifically reacts to the epithelium of PPs and isolated lymphoid follicles. Target antigen was analyzed by immunoprecipitation and mass spectrometry. Localization and expression of target antigen were evaluated by immunofluorescence, in situ hybridization and real-time PCR.

Results

Immunoprecipitation and mass spectrometry revealed that mAb 10-15-3-3 recognized apolipoprotein A-IV (ApoA-IV), a well-known lipid transporter; this finding was confirmed by the specific reactivity of mAb 10-15-3-3 to cells transfected with the murine ApoA-IV gene. Immunofluorescence using mAb 10-15-3-3 showed intestinal localization of ApoA-IV, in which strong expression of the ApoA-IV protein occurred throughout the entire intestinal epithelium during developing period before weaning but was restricted to the FAE in adult mice. In support of these findings, in situ hybridization showed strong expression of the ApoA-IV gene throughout the entire intestinal epithelium during developing period before weaning, but this expression was restricted to the FAE predominantly and the tips of villi to a lesser extent in adult mice. Deficiency of ApoA-IV had no effect on the organogenesis of PP in mice.

Conclusions

Our current results reveal ApoA-IV as a novel FAE-specific marker especially in the upper small intestine of adult mice.     

Upfront autologous stem-cell transplantation with melphalan,cyclophosphamide, etoposide,and dexamethasone (LEED) in patients with newly diagnosed primary central nervous system lymphoma

Treatment of primary central nervous system lymphoma (PCNSL) improved in recent years. However, the high neurotoxicity and low survival rates associated with this condition remain unresolved. We report 13 consecutive patients with PCNSL for whom upfront melphalan, cyclophosphamide, etoposide, and dexamethasone (known as LEED) followed by autologous stem-cell transplantation (ASCT) was planned at the Anjo Kosei Hospital. All patients were pathologically diagnosed with diffuse large B-cell lymphoma and were negative for human immunodeficiency virus. All patients were to receive three cycles of high-dose methotrexate-based induction chemotherapy, two cycles of high-dose AraC-based chemotherapy, and LEED followed by ASCT. All 13 patients achieved a partial response, and the 3-year overall survival (OS) rate was 76.2 %. Seven of the 13 patients were alive at the last follow-up, without any adverse events, including neurotoxicity. Six of the 13 (46.2 %) patients underwent ASCT and the 3-year OS rate was 80.0 %. Although this study included only a limited number of patients, these preliminary signs of efficacy and tolerability merit further consideration. To make further improvements in survival, the rate of patients undergoing ASCT should be increased. Other prospective studies involving greater numbers of patients are required to confirm these findings.