Title: pancreatic-type mixed acinar neuroendocrine carcinoma of the stomach: a case report and review of the literature.

BACKGROUND: The majority of gastrointestinal tumors are adenocarcinomas. Rarely, there are other types of tumors, such as acinar cell carcinoma, and these are often called pancreatic-type acinar cell carcinomas. Among these tumors, some are differentiated into neuroendocrine components. A few of them are MiNENs. CASE PRESENTATION: The patient was an 80-year-old male who was referred to our hospital for treatment of a pedunculated gastric tumor. It was 5 cm in diameter and detected in the upper gastric body with upper GI endoscopy conducted to investigate anemia. In the biopsy, although hyperplasia of gastric gland cells was noted, no tumor cells were found. Retrospectively, the diagnosis was misdiagnosed. An operation was arranged because bleeding from the tumor was suspected as a cause of anemia and because surgical resection was considered to be desirable for accurate diagnosis. Hence, laparoscopic and endoscopic cooperative surgery was performed. In the pathological examination, several types of epithelial cells that proliferated in the area between the mucosa and deep inside the submucosa were observed. These consisted of acinar-glandular/trabecular patterns and solid. A diagnosis of pancreatic-type acinar cell carcinoma of the stomach with NET G2 and G3 was made based on characteristic cellular findings and the results of immunostaining tests. Each of them consisted of more than 30% of the lesion; a diagnosis of pancreatic-type mixed acinar neuroendocrine carcinoma (pancreatic-type MiNEN) of the stomach or a type of gastric MiNEN was obtained. Anemia was resolved after the operation, and the patient was discharged from the hospital without perioperative complications. CONCLUSIONS: Pancreatic-type ACC of the stomach that is differentiated into neuroendocrine tumors is very rare. Hence, we report this case along with a literature review.

Follicular lymphoma-related colitis resembling ulcerative colitis.

Among the various manifestations of colonic involvement in malignant lymphomas, an ulcerative colitis-like appearance is rare. Herein, we describe a case in which extranodal colonic involvement resembled ulcerative colitis in a patient with advanced follicular lymphoma. A 59-year-old Japanese man with diarrhea and body weight loss was referred to our hospital. Computed tomography (CT) revealed systemic lymphadenopathy, splenomegaly, and thickening of the sigmoid colon and rectum walls. 18F-fluorodeoxy-glucose positron emission tomography (18F-FDG-PET/CT) revealed intense tubular 18F-FDG accumulation extending from the rectum to the colon at the hepatic flexure and much weaker accumulation in the systemic lymph nodes, bone marrow, and spleen. The isotope-enriched areas had an ulcerative colitis-like appearance as shown via colonoscopy. The patient was ultimately diagnosed with follicular lymphoma (stage IV A, grade 1) based on a pathological examination of the neck lymph nodes, iliac bone marrow, and colon. After six courses of chemotherapy (R-CHOP), 18F-FDG-PET/CT confirmed complete remission of the lymphoma including the colonic lesion. This is presumably the first case of ulcerative-like colitis caused by a follicular lymphoma. As a novel approach, the lymphoma-related colitis was detected by comparing the pathology results and the 18F-FDG-PET/CT results.

[A case of effective treatment with UFT/LV chemotherapy for para-aortic lymph node metastasis from colonic cancer 8 years after colectomy].

A 77-year-old woman was admitted to our hospital because of para-aortic lymph node swelling pointed out by abdominal CT scan. She had a previous history of colectomy with a diagnosis of ascending colonic cancer 8 years later. Pathological examination was a moderately-differentiated adenocarcinoma with lymph node metastasis (Stage IIIa). PET scan demonstrated hot spots of para-aortic and left supra-clavicular lesions. The serum CEA and CA19-9 levels regained the normal value. No malignancy was recognized by endoscopic examinations of upper and lower gastrointestinal tract. We supported that swelling of lymph nodes were due to lymphoma. Laparotomic biopsy of para-aortic lymph node was done after 6 months. Histologically metastatic adenocarcinoma was recognized. We performed systemic chemotherapy of UFT and LV on recurrent colonic cancer. After 9 courses, spots of para-aortic and left supra-clavicular lesions disappeared on the PET scan. Lymph node metastasis was not found by CT scan 20 months after beginning chemotherapy. Thus, we consider that this therapy was recommendable for the treatment of an older adult patient with recurrent colonic cancer.

Participation of liver cancer stem/progenitor cells in tumorigenesis of scirrhous hepatocellular carcinoma--human and cell culture study.

Cancer stem cells reportedly participate in the tumorigenesis of some neoplasms. Scirrhous hepatocellular carcinoma is a variant of hepatocellular carcinoma with abundant fibrous stroma. Herein, we clinicopathologically examined scirrhous (29 cases) and conventional (50 cases) hepatocellular carcinoma with reference to cancer stem cells. Scirrhous hepatocellular carcinoma was classifiable into 3 types based on small neoplastic cells at the periphery of tumor cell nests. Of 29 cases of scirrhous hepatocellular carcinoma, 21 contained small neoplastic cells. Immunohistochemically, those cells were positive for cytokeratin 7 and ATP-binding cassette transporter G2. In 11 cases, those small tumor cells were also positive for cytokeratin 19, neural cell adhesion molecule, and epithelial cell adhesion molecule (type 1), whereas 10 cases did not show such additional expression (type 2). The remaining 8 tumors did not contain small tumor cells with stem cell features (type 3). In the central parts of tumor nests, carcinoma cells got hepatocellular markers and lost expression of neural cell adhesion molecule, and epithelial cell adhesion molecule, suggesting hepatocellular maturation. Transforming growth factor beta1, a fibrogenic cytokine, was also detected in those small tumor cells. Culture cells extracted as "side population" from hepatocellular carcinoma cell lines (HuH7 and PLC5) expressed more intensely cytokeratins 7 and 19, neural cell adhesion molecule, epithelial cell adhesion molecule, and transforming growth factor beta1 than did non-side population cells. Small tumor cells with stem cell features in scirrhous hepatocellular carcinoma may correspond to side population of culture cells and might be involved in fibrogenesis of scirrhous hepatocellular carcinoma.

Occurrence of the Fimbria Gene hifA in clinical isolates of nonencapsulated Haemophilus influenzae.

The adherence of Haemophilus influenzae to epithelial cells plays a crucial role in infections. However, little is known about the occurrence of fimbriae. In this study, we examined the distribution of the fimbria gene (hifA) by PCR among 167 H. influenzae strains isolated from patients with respiratory infections. Almost all (163; 98%) of the isolates were nonencapsulated strains. The carriage rate of hifA by the nonencapsulated strains was 18.4%. Electron microscopy showed that fimbriae were abundantly present on the cell surface of hifA-positive strains tested. Only four (2.4%) isolates were encapsulated, all of which were type b and did not possess hifA. The present work suggests that fimbriae may play a considerable role as adhesins in nonencapsulated H. influenzae strains.

Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttner's tumor).

Chronic sclerosing sialadenitis (CSS) is a cryptogenic tumor-like condition of the salivary gland(s). While immune-mediated processes are suspected in its pathogenesis, and CSS is occasionally reported to be associated with sclerosing pancreatitis, an IgG4-related disease, the exact immunopathologic processes of CSS remain speculative. In this study, we examined the clinicopathologic findings of CSS (12 cases) in comparison with sialolithiasis (8 cases) and Sjogren's syndrome (13 cases), and tried to clarify whether CSS is an IgG4-related disease or not. Submandibular gland(s) were affected in all cases of CSS. CSS cases could be divided into two types: 5 cases were associated with sclerosing lesions in extrasalivary glandular tissue (systemic type), while only salivary gland(s) were affected in the remaining 7 cases (localized type). In the former type, which showed male predominance, bilateral salivary glands were frequently affected, and eosinophilia and elevations of gamma-globulin and IgG in serum were frequently found. Histologically, all cases of CSS showed marked lymphoplasmacytic infiltration admixed with fibrosis and the destruction of glandular lobules. Obliterative phlebitis was found in the affected salivary glands in all cases of CSS. Immunohistochemically, the proportion of IgG4/IgG-positive plasma cells was more than 45% in CSS, while it was less than 5% in controls. The resemblance of the clinicopathologic features of CSS with those of sclerosing pancreatitis suggests the participation of a similar immunopathologic process with IgG4 disturbance in CSS. The abundance of IgG4-positive plasma cells in the lesions would be useful for distinguishing CSS from other forms of sialadenitis.

[Effects of radiation therapy for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer].

Effects of radiation therapy for lymph node metastases from gastric cancer were retrospectively analyzed. The radiation sites were residual paraaortic lymph node involvement and postoperative recurrent lymph node metastases in 10 patients. The size of lymph node swelling was decreased in 6 (60%) patients after radiation therapy using liniac. Complaints due to lymph node metastases such as pain and edema of extremities were voiced by 7 patients. These complaints were eventually relieved or disappeared in all 7 patients. There were no severe adverse effects during radiation therapy, and 7 patients (70%) could shift to home care. One-year and 3-year survival rates were 20 and 10%, respectively. Radiation therapy for lymph node metastases from gastric cancer was chiefly effective in relieving complaints. Although it is unclear whether radiation therapy can improve the survival rate, these results suggest that radiation therapy could be one of the most useful locoregional therapies for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer.

Autoimmune hepatitis associated with bile duct injury resembling chronic non-suppurative destructive cholangitis.

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are representative autoimmune liver diseases in which hepatocytes and intrahepatic bile ducts, respectively, are selectively damaged by autoimmune mechanisms. Bile duct injury and loss is characteristic of PBC and chronic non-suppurative destructive cholangitis (CNSDC), in particular, is a histological hallmark of PBC. In this report, we present an unusual case of AIH accompanied by CNSDC-like bile duct injury in a 46-year-old woman. The patient's serum aminotransferase level was abnormally high. The serum levels of alkaline phosphatase, gamma-GTP and IgG were also elevated, but the IgM level was within normal limits. The titer of antismooth muscle antibody (SMA) was 1:80, while antinuclear autoantibody (ANA) and the M2 fraction of antimitochondrial antibody (AMA) were both negative. Liver biopsy disclosed CNSDC-like bile duct injuries and severe interface hepatitis and lobular hepatitis with perivenular zonal necrosis were observed. The aggregate score of the International Autoimmune Hepatitis Group corresponded to the category of probable AIH. Immunohistochemically, histocompatibility leukocyte antigen-DR, which is aberrantly expressed in the damaged bile ducts of PBC, was not found in the injured bile ducts of this case. Laboratory data were much improved by treatment with prednisone, but ursodeoxycholic acid was not effective. Although the possibility of an overlapping syndrome of AIH- and AMA-negative PBC could not be excluded, this case was diagnosed as AIH with CNSDC-like bile duct lesions.

Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of a case.

In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, RNA probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer.

Massive hemorrhage in a patient with intestinal Behçet's disease: report of a case.

Major gastrointestinal bleeding is a rare manifestation of intestinal Behçet's disease. We report herein the case of a 64-year-old man with intestinal Beh,et's disease complicated by myelodysplastic syndrome who suffered massive hemorrhage. Colonoscopy demonstrated ulceration of the entire colon from the cecum to the rectum, characterized by punched-out ulcers. Angiography demonstrated apparent extravasation of contrast material in the terminal ileum, and embolization was not successful. Continued and massive bleeding necessitated surgical resection of the involved segment of ileum; however, massive bleeding recurred. Re-endoscopy showed oozing hemorrhage from the multiple colon ulcerations. Intra-arterial prednisolone injection therapy was given, following which the melena gradually subsided and completely stopped within a few days.

Overlap of idiopathic portal hypertension and scleroderma: report of two autopsy cases and a review of literature.

Idiopathic portal hypertension (IPH) is characterized by dense fibrosis of portal tracts and portal venous obliteration. Little is known about the etiopathogenesis of IPH. Association of various autoimmune diseases such as systemic lupus erythematosus in IPH suggests that IPH may share immunological disturbances with such autoimmune diseases. We recently experienced two autopsy cases presenting with both diffuse scleroderma and IPH. Dense fibrosis was found in both the dermis and intrahepatic portal tract of these cases. In addition, small vascular damages were commonly observed to various degrees in these fibrotic areas of both organs. The activation of fibroblasts and vascular damages mediated by various growth factors and cytokines reportedly involved in the dermis in scleroderma might have also been operative in portal tracts in these two cases of IPH. A review of literature disclosed eight overlapping cases of IPH and scleroderma (middle- to old-aged females), and scleroderma was diagnosed earlier than IPH. These findings suggest that similar pathogenetic processes are operative in the dermis as well as in the portal tracts of the liver in these cases.