Shoichiro Mukai

Submucosal Invasive Micropapillary Carcinoma of the Colon with Massive Lymph Node Metastases: A Case Report

Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases.

Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors

Objective: To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. Methods: The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of miR-24, miR-143, and miR-145 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of miR-24, miR-143, and miR-145 in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of miR-24 and miR-143 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of miR-24 was an independent predictor for the exposure status. Conclusion: These results suggest that the measurement of miR-24 expression from FFPE samples is useful to identify radiation-associated GC.

Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype.

Objective: Gastric cancer (GC) is one of the most common human cancers. A useful method of gastric cancer stem cell (CSC) characterization is spheroid colony formation. Previously, we reported that KIF11 expression is >2-fold in spheroid-body-forming GC cells compared with parental cells. Here, we analyzed the expression and distribution of KIF11 in human GC by immunohistochemistry. Methods: Expression of KIF11 in 165 GC cases was determined using immunohistochemistry. For mucin phenotypic expression analysis of GC, immunostaining of MUC5AC, MUC6, MUC2 and CD10 was evaluated. RNA interference was used to inhibit KIF11 expression in GC cell lines. Results: In total, 119 of 165 GC cases (72%) were positive for KIF11. Expression of KIF11 was not associated with any clinicopathologic characteristics; however, it was observed frequently in GC exhibiting an intestinal phenotype. Both the number and size of spheres formed by MKN-74 cells were significantly reduced following transfection of KIF11-targeting siRNA compared with negative-control siRNA. Furthermore, levels of phosphorylated Erk1/2 were lower in KIF11 siRNA-transfected cells than with negative-control siRNA-transfected cells. Conclusion: These results indicate that KIF11 is involved in intestinal mucin phenotype GC.

Overexpression of PCDHB9 promotes peritoneal metastasis and correlates with poor prognosis in patients with gastric cancer

Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, may be useful biomarkers for cancer diagnosis and therapeutics. In the present study, we focused on the PCDHB9 gene, which encodes the transmembrane protein protocadherin B9. Immunohistochemical analysis revealed that 62 (36%) of 173 GC cases were positive for protocadherin B9. Protocadherin B9 staining was mainly observed on the GC cell membrane. Expression of protocadherin B9 was frequently found in intestinal‐type GC and correlated with poor prognosis in patients with intestinal‐type GC. Although PCDHB9 knockdown or forced expression of PCDHB9 did not change cell growth or invasion activity in a GC cell line, cell adhesion to fibronectin was significantly reduced by PCDHB9 knockdown and significantly enhanced by overexpression of PCDHB9. Expression levels of ITGA3, ITGA4, ITGA5, and ITGB1 were significantly reduced by knockdown of PCDHB9 and significantly enhanced by overexpression of PCDHB9. Furthermore, both the number and the size of spheres in culture were significantly decreased by PCDHB9 knockdown and significantly increased by overexpression of PCDHB9. In a peritoneal dissemination mouse model, the weight of the total disseminated nodules of MKN‐74 cells was significantly increased by forced expression of PCDHB9. These results indicate that protocadherin B9 plays an important role in the progression rather than the pathogenesis of intestinal‐type GC. Specific inhibitors of protocadherin B9 may constitute promising anti‐cancer drugs with fewer side‐effects. Copyright

Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer

Bladder cancer, the majority of which is urothelial carcinoma (UC), is a common malignancy worldwide. Genes encoding transmembrane/secretory proteins expressed specifically in certain cancers may be ideal biomarkers for cancer diagnosis and may represent therapeutic targets. In the present study, the expression and function of the bone marrow stromal cell antigen 2 (BST2) gene was analyzed in UC. Reverse transcription-quantitative polymerase chain reaction demonstrated that expression of BST2 in normal tissue samples was the highest in liver tissue. However, expression of BST2 in UC tissue samples was higher than in normal liver. Immunohistochemical analysis revealed weak or no staining of BST-2 in non-neoplastic mucosa, whereas UC tissue exhibited stronger and more extensive staining compared with non-neoplastic mucosa. BST-2 staining was observed mainly on UC cell membranes. In total, 28 (41%) of 69 UC cases were positive for BST-2. UC cases positive for BST-2 were more frequently T2/3/4 cases [so-called muscle-invasive bladder cancer (MIBC)] than Ta/is/1 cases (P=0.0001). However, Kaplan-Meier analysis demonstrated no association between BST-2 expression and survival. BST2 small interfering RNA (siRNA)-transfected T24 cells exhibited significantly reduced cell growth relative to negative control siRNA-transfected T24 cells. The levels of phosphorylated Akt and extracellular signal-regulated kinase were lower in BST2 siRNA-transfected T24 cells than in control cells. These results suggest the involvement of BST-2 in the pathogenesis of UC. Since BST-2 is expressed on the cell membrane, BST-2 may be a good therapeutic target for MIBC.

A prospective study of the safety and usefulness of a new miniature wide-angle camera: the “BirdView camera system”

BackgroundThe performance of endoscopic surgery has quickly become widespread as a minimally invasive therapy. However, complications still occur due to technical difficulties. In the present study, we focused on the problem of blind spots, which is one of the several problems that occur during endoscopic surgery and developed “BirdView,” a camera system with a wide field of view, with SHARP Corporation.MethodsIn the present study, we conducted a clinical trial (Phase I) to confirm the safety and usefulness of the BirdView camera system. We herein report the results.ResultsIn this study, surgical adverse events were reported in 2 cases (problems with ileus and urination). There were no cases of device failure, damage to the surrounding organs, or mortality.ConclusionsWe evaluated the safety of the BirdView camera system. We believe that this camera system will contribute to the performance safe endoscopic surgery and the execution of robotic surgery, in which operators do not have the benefit of tactile feedback.

Laparoscopic management of refractory chylous ascites using fluorescence navigation with indocyanine green: A case report

Highlights • It is frequently difficult to detect the site of lymphatic leakage intraoperatively.• Intraoperative ICG injection is useful for identifying lymphatic leakage sites.• Intraoperative ICG injection is a simple technique with fewer adverse effects.• Laparoscopic surgery is safe and effective for refractory chylous ascites.

Small bowel obstruction due to an unconjugated ursodeoxycholic acid enterolith following living donor liver transplantation: Report of a case

We report an unusual case of small bowel obstruction due to an ursodeoxycholic acid (UDCA) enterolith that occurred 7 years after liver transplantation. A 70‐year‐old man had undergone multiple operations, including a living donor liver transplantation (LDLT) and hepaticojejunostomy. Four years after the LDLT, cholestasis developed, for which oral UDCA was administrated. Seven years after the LDLT, he was admitted to our hospital because of pneumonia; intestinal obstruction occurred following its resolution. A radiographic contrast study and computed tomographic scan indicated a movable mass as the cause of the ileus, suggesting a giant stone. We were unable to observe or remove the stone by double balloon enteroscopy owing to the presence of severe adhesion; thus, we surgically removed the mass. The patients postoperative course was uneventful. He was discharged 20 days after the operation. An infrared spectrophotometric analysis revealed that the stone was a true enterolith, primarily composed of unconjugated UDCA. An ileus caused by a true enterolith is a rare clinical complication of LDLT. Nevertheless, it must be considered in the differential diagnosis of intestinal obstructions in liver transplant recipients with Roux‐en‐Y hepaticojejunostomies and/or bowel stasis.

Abstract 1413: Significance of KIFC1 in spheroid formation of gastric cancer cells

Spheroid colony formation is a typically method to identify cancer stem cells (CSC). The growth of spherical colonies is considered indicative of self-renewal ability, and is consistent with a CSC phenotype. However, mechanism of spheroid formation remains unclear in gastric cancer (GC). In the present study, we analyzed spheroid formation associated genes in GC. Comprehensive gene expression profile of MKN-45 and MKN-74 GC cell lines that were grown as monolayers or spheroids was obtained by Affymetrix GeneChip, and we found several kinds of genes whose expression was up-regulated or down-regulated in cells that were grown as spheroids. Among these, 10 kinds of kinesin genes were up-regulated in both MKN-45 and MKN-74 cells that were grown as spheroids. Kinesins are categorized into 14 subfamilies and classified as mitotic kinesins, which are involved in cell division, and non-mitotic kinesins, which are principally involved in intracellular transport. In spheroids, mitotic kinesins were up-regulated. In the present study, we focused on KIFC1, because antibody against KIFC1 is available. qRT-PCR analysis revealed that up-regulation of KIFC1 in both MKN-45 and MKN-74 cells that were grown as spheroids. Immunohistochemical analysis of KIFC1 was performed in 20 GC cases. Expression of KIFC1 was up-regulated in GC tissues in comparison with corresponding non-neoplastic mucosa. These results suggest that KIFC1 plays an important role in gastric carcinogenesis and may be a therapeutic target of GC. Citation Format: Naohide Oue, Shoichiro Mukai, Trang Pham T.B., Kazuhiro Sentani, Reiko Ito, Wataru Yasui. Significance of KIFC1 in spheroid formation of gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1413. doi:10.1158/1538-7445.AM2015-1413

A case of ascending colon cancer accompanied with tumor thrombosis in the superior mesenteric vein treated with right hemicolectomy and greater saphenous vein grafting

Highlights • The occurrence of colorectal cancer with tumor thrombosis in the mesenteric vein is very rare.• Complete resection of the primary cancer with tumor thrombosis is essential.• Combined surgery and chemotherapy should be performed to prevent recurrence.