Clinicopathologtcal Study of Serrated Polyps of the Colorectum, with Special Reference to Maspin Expression

Aims: We compared the clinicopathologic features of three types of colorectal serrated polyps, namely, hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs), and analyzed the expression pattern of maspin in these serrated lesions. We retrospectively examined 173 polypoid lesions that were endoscopically excised from 136 patients and diagnosed as hyperplastic or adenomatous serrated lesions, and histologically classified as HPs, SSA/Ps, or TSAs. Maspin expression was immunohistochemically examined in all lesions. Overall, 59 lesions (34%) were classified as HPs, 70 (40%) as SSA/Ps and 44 (25%) as TSAs. There were no significant differences in mean age or gender of patients between types, but SSA/Ps frequently developed on the right colon and showed a superficial/flat elevation, whereas HPs and TSAs frequently developed on the left colon and showed protruded lesions. The average diameters of HPs, SSA/Ps, and TSAs were 7.2, 9.9, and 12.9mm, respectively, showing significant differences. Diffuse cytoplasmic expression of maspin was observed in the serrated glands of all three types. In addition, focal or diffuse intranuclear localization of maspin was observed in 15% of HPs, 13% of SSA/Ps, and 84% of TSAs, showing significant differences between TSAs and the other two types. The three types of serrated polyp examined in this study showed distinct clinicopathological features. The presence of maspin expression in these polyps, regardless of whether they were hyperplastic or neoplastic, indicates that maspin might be commonly associated with cell proliferation, although the underlying mechanism might be different between types

An Autopsy Case of Multiple Jejunal Diverticula Showing Severe Malabsorption

A rare autopsy case of multiple jejunal diverticula showing severe malabsorption is reported. A 56-year-old man was admitted due to vomiting and leg edema. On admission, his height was 160cm, his body weight was 39kg, and laboratory data revealed severe hypoproteinemia (TP: 4.0g/dl, ALB: 2.1g/dl). On the 14th day of admission, agonal breathing and disturbance of consciousness occurred after massive vomiting of gastric juice, and the patient died of respiratory failure. At autopsy, on abdominal sectioning, multiple diverticula situated on the mesenterium side of the enteron extending 70cm in length from the proximal jejunum were identified. However there were no findings suggesting perforation or diverticulitis. Histologically, the diverticula were lined by ordinal jejunum mucosa associated with muscularis mucosa, but the muscularis propria was not involved in the diverticular walls. The diverticula were identified as false diverticula. In both lower lungs, aspiration pneumonia was widely seen. The cause of death was considered to be aspiration pneumonia due to the vomiting caused by multiple jejunal diverticula.Only 16 case reports of multiple jejunal diverticulosis in Japan could be found in the literature however most of the reported complications were perforation and diverticulitis, and there were no reports of malabsorption. Therefore, the present case is significant concerning the cause of malabsorption in routine explorations

A Clinicopathological Study of Primary Small Intestinal Cancer with Emphasis on Cellular Characteristics

We examined the clinicopathological profiles and cellular characteristics of 10 cases of surgically resected primary small intestinal cancers (excluding duodenal cancers). Histological examination revealed nine adenocarcinomas and one sarcomatoid carcinoma. Invasion depth was subserosal in five cases, serosal in four cases and to the adjacent transverse colon in the remaining case. Metastasis was present in lymph node in seven cases, in distant organs in six, and in the peritoneum in seven cases. Of the 10 cases, 7 underwent postoperative chemotherapy, and 6 of the eight traceable patients died from the disease (mean period of survival: 386 days). Histomorphologically, eight of nine adenocarcinomas showed an intestinal phenotype (unclassifiable in the other) in the upper layer, while in the lower layer, there showed an intestinal phenotype and five a non-intestinal phenotyp. Immunohistochemistry revealed a mean positive rate in the upper/lower layers as follows: 93%/86% and 38%/29% by intestinal markers CDX2 and MUC2; 19%/28% and 13%/32% by pancreatobiliary markers CK7 and MUC1; and 4%/19% and 2%/9% by gastric markers MUC5AC and MUC6, respectively. Thus, the intestinal phenotype predominated in almost all small intestinal cancer in this study, although some showed a transformation to non-intestinal or hybrid phenotypes with tumor progression. Flexible management for the diversity and transformation of cellular characteristics is therefore recommended treating and diagnosing small intestinal cancers

Immunohistochemical Analysis of Various Salivary Gland Carcinomas Focusing on the Possibility of Molecular-targeted and Hormonal Therapy

This study aimed to determine the expression of c-kit, human epidermal growth factor receptor type 2 (HER2), insulin-like growth factor receptor (IGFR), estrogen receptor (ER), progesterone receptor (PgR), vascular endothelial growth factor (VEGF), c-MET, and survivin in adenoid cystic carcinomas (ACC), carcinomas ex pleomorphic adenomas (CXPA), and mucoepidermoid carcinomas (MEC) of the salivary glands. These expression levels and locations were compared to estimate the availability of molecular and hormonal targets for therapy in salivary gland carcinomas. Forty patients with a salivary gland carcinoma, diagnosed and treated at our hospital, were studied. On the basis of histopathology, 13, 12, and 15 patients were diagnosed with ACC, CXPA, and MEC, respectively. Associations between histological types were evaluated by Fisher\u27s exact test, with a significance level of P < 0.05. Compared with the other two histological types, ACC samples demonstrated significantly higher c-kit (85%), IGFR (77%), and ER (38%) expression, while CXPA demonstrated significant HER2 (75%) staining, and MEC demonstrated significant IGFR (77%) staining. The differences in expression of the tested markers among the histological types in our study suggested that c-kit- and IGFR-targeted therapy and anti-estrogen treatment could be effective in ACC, HER2-targeted therapy could be effective in CXPA, and that IGFR-target therapy could be effective in MEC of the salivary glands

Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device.

High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets