[A Case of Ascending Colon Cancer Probably Arising from a Diverticulum].

A 70's male was admitted to our hospital with complaints of anorexia and abdominal pain. CT showed thickening of the ascending colon. Colonoscopy revealed multiple diverticula of the ascending colon, but no tumor on the mucosa. The patient was diagnosed as a case of diverticulitis of the ascending colon and was advised laparoscopic ileocecal resection. The resected specimen showed wall thickening; however, no remarkable findings were observed, with the exception of multiple diverticula on the mucosal surface. Histological examination showed well-differentiated tubular adenocarcinoma extending into the serosa probably arising from the diverticulum. Chemotherapy was performed after surgery. The patient died due to peritoneal dissemination from the ascending colon cancer 14 months after surgery.

FDG-PET Findings of Intraductal Oncocytic Papillary Neoplasms of the Pancreas: Two Case Reports.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a rare pancreatic tumor. To date, there have been three case reports of IOPN which showed strong positivity on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), raising the possibility of distinguishing IOPNs from other intraductal papillary mucinous neoplasms (IPMNs) using FDG-PET. However, all three cases had large tumors, approximately 10 cm in diameter, and there are no case reports of FDG-PET findings of small IOPNs, i.e. tumors the average size of malignant IPMNs (3-5 cm). We report two cases with IOPN of average size with FDG-PET findings. Computed tomography (CT) showed a multilocular cystic lesion 4 cm in diameter with a mural nodule 1 cm in diameter (case 1) and a cystic lesion 5 cm in diameter with a papillary mural nodule 4 cm in diameter (case 2). FDG-PET showed abnormal uptake at the same location as the pancreatic tumor revealed by CT in both cases. The maximum standardized uptake values of the lesions were 3.4 and 4.2, respectively. Surgical resection was performed and the tumor was diagnosed as IOPN with carcinoma in situ (case 1) and IOPN with minimal invasion (case 2). FDG-PET may be useful for diagnosing malignancy in IOPN, as it is in IPMN. However, in our two cases, strong accumulation was not observed in the IOPNs, which were within the average size range of malignant IPMNs.

[Computed tomography colonography for 5 cases of pneumatosis cystoides intestinalis].

Computed tomography colonography (CTC) was performed in 5 patients with pneumatosis cystoides intestinalis (PCI). The virtual colonoscopy view of CTC as well as total colonoscopy (TCS) findings showed polypoid lesions in the colon, and multiplanar reconstruction images of the colon revealed in the polypoid lesions of the colon. We confirmed the diagnosis of PCI in all cases. CTC also detected the PCI lesions in the subserosa of the colonic wall which were not detected by TCS. Accurate evaluation of the extent of PCI involvement was obtained by CT air-contrast enema images. CTC is useful for detection of PCI lesions, assessment of the exact site and final diagnosis for PCI.

Ductal adenocarcinoma of the pancreas with psammomatous calcification: report of a case with immunohistochemical study for bone morphogenetic protein.

We report a case of invasive ductal adenocarcinoma of the pancreas with psammomatous calcification. A 57-year-old man was admitted to our hospital complaining of abdominal pain and vomiting. Carcinoma of the head of the pancreas was diagnosed based on precise clinical examinations. A subtotal stomach-preserving pancreaticoduodenectomy was subsequently performed. Histological examination of the surgical specimen revealed a well-differentiated adenocarcinoma composed of irregular tubular structures involving the head of the pancreas. Conspicuously, numerous tiny psammomatous-type calcifications were observed, mainly within the neoplastic lumen, but also in association with carcinoma cells that had infiltrated the lymphatics and lymph nodes. In addition, expression of bone morphogenetic protein, cartilage and bone-inducing factor cloned from demineralized bone matrix and the transforming growth factor-ß subfamily was immunohistochemically examined for carcinoma cells. Reactivity for multiple kinds of bone morphogenetic protein (types 5, 6 and 7) was identified in the cytoplasm of carcinoma cells. Psammoma body formation is an unusual event in invasive ductal adenocarcinoma of the pancreas, with only one similar case previously reported in the English literature. We also discuss the formation of psammomatous calcifications by pancreatic cancer cells.

[A case of extrahepatic portal vein aneurysm with massive thrombosis].

A 59-year-old woman, who was given a diagnosis of portal vein aneurysm at another hospital 2 years previously, visited our institution complaining of abdominal pain in November 2005. Abdominal imaging including computed tomography and ultrasonography demonstrated that the portal vasculature had dilated to 5 cm in maximum dimension and its center was at the junction of the superior mesenteric vein and the splenic vein. Moreover, a large thrombus was seen in the portal vein, the superior mesenteric vein and the splenic vein. She was conservatively followed-up with warfarin. After 6 months, angiography revealed cavernous transformation around the portal vein was found with collateral flow toward the liver. At the time of writing the patient's condition is stable with neither extension of the thrombus nor constriction of the esophageal varices.

Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptor-interacting protein and inhibition of lysosomal cathepsin.

In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho0 cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the rho0 cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented rho0 cells (ATP-rho0), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP- rho0 cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho0 cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.

[Telangiectatic focal nodular hyperplasia accompanied with hemorrhage and necrosis during the course: report of a case].

A tumor, which was 10 cm in diameter, was found in the lateral segment of the liver of a 42-year-old man in October, 2004. The lesion was clinically diagnosed as focal nodular hyperplasia (FNH). In March, 2006, the patient admitted our hospital complaining epigastralgia, back pain, and fever. Hemorrhage and necrotic region was revealed within the tumor, hence lateral segmentectomy was carried out. The lesion was pathologically diagnosed as a telangiectatic FNH (T-FNH). A possibility that hemorrhage or necrosis may be induced within a T-FNH during its progress should be taken into consideration.

Reactive lymphoid hyperplasia of the liver: a case report and review of literature.

A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for further evaluation of hepatic tumors incidentally discovered at another hospital. Various diagnostic methods, including ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and hepatic angiography displayed three small lesions in the liver with outstanding findings consistent with hepatocellular carcinoma (HCC). Surgical resection was performed and the three lesions were microscopically diagnosed as RLH of the liver. The lesions comprised a massive infiltration of lymphoid cells with follicles and hyalinized inter-follicular spaces. Immunohistochemical examination revealed that infiltrating lymphocytes had no prominent nuclear atypia and polyclonality. RLH of the liver is a very rare condition and only twelve cases have been reported in the English literature. Majority of the reported cases were middle-aged women and about half of them had some immunologic abnormalities such as autoimmune thyroiditis, Sjogren's syndrome, primary immunodeficiency, primary biliary cirrhosis. Since they are often clinically misdiagnosed as HCC, surgery is the choice of treatment for these patients. Although their pathology resembles malignant lymphoma, the clinical course is completely benign. The authors propose that RLH of the liver can be discriminated from HCC by its clinical features.

Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.

BACKGROUND: Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay. RESULTS: A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged. CONCLUSIONS: Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.

Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.

We came across a rare case of acute megakaryocytic leukemia, the clinical course of which was relatively chronic and nonaggressive. This case was complicated with generalized severe osteosclerosis (OS). The medium in which blastic cells from the patient were cultured showed a strong activity to enhance the expression of an osteosclerotic cytokine, osteoprotegerin (OPG), as revealed by real-time quantitative RT-PCR and Western blot analysis. The OPG-inducing activity of the culture medium was neutralized by the anti-interleukin-11 (IL-11) antibody. These results indicate that IL-11 produced by the blasts was a causative factor of the OS observed in this patient.

Advanced pancreatic carcinoma showing a complete response to arterial infusion chemotherapy.

We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.

Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells.

Generation of reactive oxygen species (ROS) and activation of caspase cascade are both indispensable in Fas-mediated apoptotic signaling. Although ROS was presumed to affect the activity of the caspase cascade on the basis of findings that antioxidants inhibited the activation of caspases and that the stimulation of ROS by itself activated caspases, the mechanism by which these cellular events are integrated in Fas signaling is presently unclear. In this study, using human T cell leukemia Jurkat cells as well as an in vitro reconstitution system, we demonstrate that ROS are required for the formation of apoptosome. We first showed that ROS derived from mitochondrial permeability transition positively regulated the apoptotic events downstream of mitochondrial permeability transition. Then, we revealed that apoptosome formation in Fas-stimulated Jurkat cells was clearly inhibited by N-acetyl-L-cysteine and manganese superoxide dismutase by using both the immunoprecipitation and size-exclusion chromatography methods. To confirm these in vivo findings, we next used an in vitro reconstitution system in which in vitro-translated apoptotic protease-activating factor 1 (Apaf-1), procaspase-9, and cytochrome c purified from human placenta were activated by dATP to form apoptosome; the formation of apoptosome was markedly inhibited by reducing reagents such as DTT or reduced glutathione (GSH), whereas hydrogen peroxide prevented this inhibition. We also found that apoptosome formation was substantially impaired by GSH-pretreated Apaf-1, but not GSH-pretreated procaspase-9 or GSH-pretreated cytochrome c. Collectively, these results suggest that ROS plays an essential role in apoptosome formation by oxidizing Apaf-1 and the subsequent activation of caspase-9 and -3.

[Usefulness of CT arteriography for transcatheter peripancreatic arterial embolization to patients with advanced pancreatic cancer].

We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.

[Three cases of multiple liver metastases of carcinoid tumor responding to hepatic arterial infusion chemotherapy using degradable starch microspheres].

We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.

[A case of large-cell lung cancer with liver metastasis successfully treated using combination chemotherapy with CDDP and vinorelbine].

A 38-year-old woman presented to our hospital with the chief complaint of dyspnea. A chest radiograph showed pleural effusion of the right lung and a CT scan revealed liver metastasis. A tumor biopsy done under bronchoscopy revealed large-cell carcinoma of the lungs. She was given 4 courses of a combination therapy consisting of CDDP (80 mg/m2) and vinorelbine (25 mg/m2). The primary tumor in the right lung and liver metastasis were markedly reduced in size and a partial response was obtained. The combination therapy of CDDP and vinorelbine may become a standard chemotherapy for advanced non-small cell lung cancer.