[Effect of Proteinuria in Patients Receiving Anti-VEGF Therapy for Advanced Colorectal Cancer].

Grade 2 or 3 proteinuria was observed in 54 patients out of 158 metastatic colorectal cancer patients receiving anti-VEGF therapy. Patients with diabetes and hypertension were risk for severe proteinuria. ARBs were more frequently used in patients with severe proteinuria. However, they could not reduce proteinuria. The examination of protein/creatinine ratio was useful for continuing anti-VEGF therapy.

First Case Report of a Huge Giant Cell Tumor of Soft Tissue Originating from the Retroperitoneum.

BACKGROUND Giant cell tumor of soft tissue (GCT-ST) is a rare disease generally generated from superficial tissue. We report an extremely rare case of giant cell tumor of soft tissue arising from retroperitoneal tissue. CASE REPORT A 78-year-old man visited our medical center with the chief complaint of fatigue and weight loss for 1 month. He had a hard and immobilized mass without pain in the left upper quadrant. Contrast-enhanced CT showed a huge tumor (22×20×16 cm) in the retroperitoneal space, and it invaded into the stomach, colon, pancreas, spleen, and left kidney. MRI demonstrated the tumor had a serous cystic component as T1 was low, T2 was high, and DWI was slightly high. We diagnosed the retroperitoneal malignant tumor, and tumor resection was performed with total gastrectomy, partial colectomy, distal pancreatectomy, left nephrectomy, and left adrenalectomy for complete resection, without any postoperative complications. The tumor predominantly consisted of a solid mass, and had necrotic lesions, cystic lesions, and calcification. The histological exam showed it was composed of spindle and multinucleated giant cells; however, there was no cellular atypia or pleomorphism. Immunohistochemical staining characterized the tumor with CD68+, SMA+, CD34-, Desmin-, and S-100-. We finally diagnosed it as GCT-ST with the intermediate group of malignancy, according to WHO criteria. Thereafter, the patient had no recurrence at 1 year after resection. CONCLUSIONS The huge GCT-ST arising from the retroperitoneal space, which has never before been reported, was successfully resected. We report it with pathological findings to add to the relevant literature.

Frequent activation of mitogen-activated protein kinase relative to Akt in extrahepatic biliary tract cancer.

BACKGROUND: Lack of effective adjuvant therapy against advanced extrahepatic biliary tract carcinoma (BTC) requires that new therapeutic methods, such as molecular targeted therapy, be developed. The mitogen-activated protein kinase (MAPK) and Akt signaling pathways, which activate cell proliferation and suppress apoptosis, respectively, may function as important targets for such therapies. The aim of this study was to examine the expression patterns of phosphorylated MAPK (p-MAPK) and phosphorylated Akt (p-Akt) proteins in BTC cell lines and clinical specimens. METHODS: Expression of p-MAPK and p-Akt proteins in four human BTC cell lines and in frozen sections of 20 advanced extrahepatic BTC specimens was analyzed by Western blotting. Thirty formalin-fixed BTC specimens were immunohistochemically stained for p-MAPK and p-Akt using labeled streptavidin-biotin conjugates. RESULTS: Expression of p-MAPK was observed in three of four (75%) BTC cell lines, whereas no expression of p-Akt was observed. Twenty-three of 30 formalin-fixed specimens stained positive for p-MAPK (77%), whereas only 47% stained positively for p-Akt. Expression of p-MAPK relative to that of p-Akt was also seen more frequently in the frozen specimens. CONCLUSIONS: The results of this study suggest that MAPK is activated more frequently than Akt in extrahepatic biliary tract carcinoma.

Surface charge-transfer complex formation of catechol on titanium(IV) oxide and the application to bio-sensing.

Adsorption properties of 2-hydroxyphenol (catechol) on TiO2 particles has been studied at 298K. The adsorption proceeds from the aqueous solution with the Langmuir type behavior. Diffuse reflectance infrared spectra of the catechol-adsorbed TiO2 suggested that catechol is adsorbed on TiO2 solution via the chelation to the surface Ti ions. The adsorption induces a strong absorption in the whole visible region, of which intensity increases with an increase in the adsorption amount. Photoelectrochemical experiments and molecular orbital calculations indicate that the absorption stems from the charge-transfer (CT) transition from the HOMO of catechol to the conduction band of TiO2. Time courses for the adsorption of catechol on mesoporous TiO2 nanocrystalline film-coated glass was traced by measuring the change in the absorbance of the CT band, and analyzed on the basis of the Langmuir model. This study would present a new simple technique for sensing of important biomolecules bearing the catechol moiety.

Inhibitory effects of etodolac, a selective COX-2 inhibitor, on the occurrence of tumors in colitis-induced tumorigenesis model in rats.

Ulcerative colitis (UC)-associated neoplasia is one of the complications seen in patients with long-standing UC. Based on many epidemiological studies, colitis is assumed to promote colon tumorigenesis. Tumorigenesis is known to be suppressed in rodents and humans by selective cyclooxygenase-2 inhibitors. However, whether these drugs would serve as protective agents against UC-associated neoplasia remains unclear. Therefore, using a colitis-induced tumorigenesis rat model, we investigated the effects of etodolac, a selective cyclooxygenase-2 inhibitor, on tumorigenesis. The following 4 groups were examined: group A, administered trinitrobenzene sulfonic acid and 1,2-dimethylhydrazine; group B, in addition to the treatment in group A, also received etodolac; group C, administered etodolac alone; and group D, did not receive any agent throughout the study and served as an untreated control. The rats were sacrificed 163 days after the start of experiment, and the number of aberrant crypt foci and tumors in the intestine were counted using a stereoscopic microscope following methylene blue staining. The mean number of aberrant crypt foci was 52.4 in group A, 18.9 in group B, 0 in group C and 0.5 in group D. A total of 9 tumors were observed in group A alone, with none in the remaining groups. The numbers of aberrant crypt foci and tumors in group B were significantly lower than in group A. Etodolac, a selective cyclooxygenase-2 inhibitor, suppresses the occurrence of aberrant crypt foci and tumors in colitis-induced tumorigenesis in rats.

Antitumor effect of gemcitabine on orthotopically inoculated human gallbladder cancer cells in nude mice.

BACKGROUND: The prognosis of gallbladder carcinoma is poor; therefore, investigating the efficacy of new chemotherapy agents is essential for the treatments for this tumor. Recently, several studies have reported clinical trials using gemcitabine as treatment for advanced gallbladder cancers. However, the antitumor effects of gemcitabine on gallbladder carcinoma have not been examined in in vitro and in vivo model systems. METHODS: We examined the cytotoxicity of gemcitabine in four biliary tract cancer cell lines using the WST-1 assay. In addition, we examined the effect of gemcitabine on gallbladder cancers resulting from orthotopic inoculation of NOZ gallbladder tumor cells into nude mice. One week after transplantation, the mice were randomized into two groups: In Group A, the mice were treated by an intra-peritoneal injection of 0.9% sodium chloride for three weeks after inoculation (control). In Group B, the mice were treated by an intra-peritoneal injection of gemcitabine (125 mg / kg) for three weeks. All mice were sacrificed one week after the end of treatment, and macroscopic and histological findings were evaluated. The expression levels of proliferating-cell nuclear antigen (PCNA) were examined to investigate cellular proliferation activity, and Tunnel assays were performed to determine apoptotic status. Survival duration of the mice after gemcitabine treatment was compared to that of untreated mice. RESULTS: The gemcitabine sensitivity of the four biliary tract cancer cell lines was similar in a dose dependent manner. In the in vivo models, the Group A mice showed huge tumors of the gallbladder, with liver invasion and lymph node metastases. However, there were no abdominal tumors in the Group B mice, and microscopic gallbladder cancer could only be detected from histological findings. The mean percent of PCNA-positive tumor cells was significantly higher in tumors from mice in Group A (71.9%) compared to those of Group B (34.7%). The mean percent of Tunnel-positive tumor cells was significantly lower in mice from Group A (2.0%) than those from Group B (5.7%). Survival duration was prolonged significantly in the gemcitabine-treated mice relative to untreated mice. CONCLUSIONS: Gemcitabine treatment may inhibit tumor progression and prolong survival in gallbladder cancer by inhibiting cell proliferation and inducing apoptosis.

Intrahepatic segmental primary sclerosing cholangitis: report of a case.

A 67-year-old woman was referred to our hospital for investigation of epigastric discomfort. Computed tomography (CT) showed dilatation of the intrahepatic bile duct in the left lobe of the liver, endoscopic cholangiography showed complete stenosis of the left main branch of intrahepatic bile duct, and CT during angiography showed decreased portal blood flow to segment 3 of the liver. Based on these findings, we suspected intrahepatic cholangiocarcinoma and performed left lobectomy of the liver. However, pathological examination revealed fibrosis and infiltration of inflammatory lymphoid cells around the stenotic bile duct and periportal area, without any evidence of malignancy. Since these findings were compatible with sclerosing cholangitis and the patient did not have a disorder that would cause secondary sclerosing cholangitis, the final diagnosis was primary sclerosing cholangitis (PSC). It is difficult to distinguish segmental PSC from cholangiocarcinoma; thus we think surgical resection is an appropriate therapeutic and diagnostic procedure for segmental intrahepatic bile duct stenosis.

Evaluation of tumor cell dissociation as a predictive marker of lymph node metastasis in submucosal invasive colorectal carcinoma.

PURPOSE: Tumor cell dissociation-the histologic finding of small solid carcinoma cell clusters and groups of dissociated dedifferentiated carcinoma cells at the invasive front-is related to tumor metastasis and patient prognosis. However, few previous reports have examined tumor cell dissociation in submucosal invasive colorectal carcinoma. We investigated the relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. We also examined immunohistochemical expression of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. METHODS: Submucosal invasive colorectal carcinoma tissue samples from 20 patients with lymph node metastasis and 100 patients without lymph node metastasis were evaluated. Sections stained with hematoxylin and eosin were evaluated for tumor cell dissociation. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin and beta-catenin. RESULTS: Tumor cell dissociation was more frequently identified in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.0001). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.025). Nuclear expression of beta-catenin tended to be present in submucosal invasive colorectal carcinoma cases with lymph node metastasis (P = 0.063). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with tumor cell dissociation than in those without tumor cell dissociation (P = 0.0023). CONCLUSIONS: Our results suggest that there is a relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. Tumor cell dissociation formation might be related to abnormal expression patterns of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Tumor cell dissociation and decreased membranous expression of E-cadherin would be important predictive markers for lymph node metastasis in submucosal invasive colorectal carcinoma.

Extranodal diffuse follicular center lymphoma mimicking mantle cell lymphoma of the intestine.

We report a case of diffuse follicular center lymphoma (FCL), which is a morphological variant of follicular lymphoma, resembling multiple lymphomatous polyposis (mantle cell lymphoma of the intestine). The patient was a 48-year-old Japanese man who was found, by colonoscopy, to have numerous small polypoid lesions along the entire large intestine. Abdominal computed tomography revealed hepatosplenomegaly and enlargement of multiple mesenteric lymph nodes. Histologically, the lesion was characterized by diffuse proliferation of small- to medium-sized lymphocytes with cleaved nuclei in the mucosa and submucosa. Immunohistochemical studies showed that the tumor cells were CD20+, CD10+, BCL-2+, CD5-, surface IgM-, and cyclin D1-. Moreover, a cytogenetic study showed a translocation at (14;18)(q32;q21). Finally, this case was diagnosed as diffuse FCL, although the tumor was mimicking mantle cell lymphoma.