Hajime Shibuya

Clinicopathological and Prognostic Value of MicroRNA-21 and MicroRNA-155 in Colorectal Cancer

Objective: The clinical significance of microRNA-21 (miR-21) and miR-155 in colorectal cancer (CRC) patients remains elusive. In this study, we established the prognostic value of miR-21 and miR-155 using clinical samples from CRC patients. Furthermore, relationships between these microRNAs and target genes (PDCD4 and TP53INP1 mRNAs) were examined. Methods: miR-21 and miR-155 expression was assessed in tumor tissue and in adjacent normal tissue of 156 CRC patients by TaqMan MicroRNA assays, and PDCD4 and TP53INP1 mRNA levels were measured by quantitative real-time reverse transcriptase PCR (RT-PCR). Results: High miR-21 expression was significantly associated with venous invasion, liver metastasis and tumor stage, and high miR-155 expression was significantly correlated with lymph node metastases. The overall (OS) and disease-free survival (DFS) rates of patients with high miR-21 expression were significantly worse than those of patients with low miR-21 expression. The OS and DFS of patients with high miR-155 expression were also significantly worse than those in patients with low miR-155 expression. miR-21 and miR-155 expression levels in CRC tissue were independent prognostic factors for OS and DFS. Significant inverse correlations were demonstrated between miR-21 and PDCD4 mRNA, and miR-155 and TP53INP1 mRNA. Conclusion: Increases in miR-21 and miR-155 expression may represent effective biomarkers for the prediction of a poor prognosis.

Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer.

BACKGROUND: KRAS status is a useful predictive marker for anti-epidermal growth factor receptor antibody therapy. OBJECTIVE: This study aimed to examine the concordance rate of KRAS mutation status between corresponding primary and metastatic colorectal cancer lesions, and also among multiple metastatic tumors. Furthermore, we examined the heterogeneity of KRAS mutations with respect to discordant KRAS status between primary and metastatic tumors. DESIGN AND SETTINGS: This study was retrospective in design. PATIENTS: Forty-three patients with primary tumors and 113 metastatic tumors were studied. MAIN OUTCOME MEASURES: The KRAS mutational status was determined by the peptide nucleic acid clamp real-time polymerase chain reaction TaqMan assay. We also performed sequencing analysis to validate the KRAS mutational status. When KRAS status differed between primary and metastatic tumors, we examined the heterogeneity of KRAS status within individual primary tumors by microdissecting multiple samples in each patient. RESULTS: The frequency of KRAS mutations in primary tumors was 34.9%. A high concordance rate of KRAS (88.4–91.7%) mutations was observed between primary and metastatic tumors. All 5 cases (11.6%) with discordant KRAS status had heterogeneous KRAS status in primary tumors. However, in 10 concordant cases all microdissected areas showed an identical KRAS mutational status within each patient. The KRAS mutational statuses in all multiple liver and/or lung metastatic tumors were the same as those of the primary tumor. LIMITATIONS: We could not validate KRAS status in microdissected samples by the direct sequence method that was used in the present study, because the quantity of DNA was not sufficient to perform direct sequencing. CONCLUSION: KRAS status in a primary site may be used for selecting patients who would benefit from anti-epidermal growth factor receptor therapy. However, KRAS status can be heterogeneous within a primary tumor, and thus different parts of such tumors should be examined for KRAS status to correctly predict the KRAS status in metastatic lesions.

Tumor location is a prognostic factor in poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma of the colon

PurposeCancers which arise in the proximal and distal colon are suggested to be different clinically, pathologically, and genetically. The aim of this study is to clarify whether clinical behavior of colonic poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-cell carcinoma (Por/Muc/Sig cancers), minor and aggressive subpopulation in colonic cancers, differs in accordance with the tumor location.MethodsA total of 3,175 patients with curatively resected colonic cancers were studied. Clinical and pathological features were compared between Por/Muc/Sig cancers and well or moderately differentiated adenocarcinomas (Wel/Mod cancers) and between proximal and distal cancers in each histologic type.ResultsPor/Muc/Sig cancers (n = 213) were more advanced in the TNM stage and showed worse disease-specific survival than Wel/Mod cancers (n = 2,692). In Por/Muc/Sig cancers, but not in Wel/Mod cancers, proximal cancers showed significantly better disease-specific survival than distal cancers (88.9% vs. 76.5%, p = 0.0234), and a multivariate analysis showed that proximal tumor location was an independent predictor of fair prognosis (hazard ratio (HR), 0.458; 95% confidence interval (CI), 0.218–0.961; p = 0.0390). In addition, female gender also was an independent predictor of fair prognosis in Por/Muc/Sig cancers (HR, 0.373; 95% CI, 0.151–0.922) and not in Wel/Mod cancers.ConclusionsProximal Por/Muc/Sig cancers were suggested to be a distinct subpopulation with a favorable oncologic outcome. Tumor location and gender might be helpful in the risk stratification after curative surgery for Por/Muc/Sig cancers.

Predictive Value of Cancer Stem-Like Cells and Cancer-Associated Genetic Markers for Peritoneal Recurrence of Colorectal Cancer in Patients after Curative Surgery

Objective: The new concept of cancer stem cells has implications in terms of possible application for novel diagnostic and therapeutic procedures. Recently, the CD133 molecule was reported as a marker of cancer stem-like cells in colorectal cancer (CRC). In this study, we examined the prognostic value of free cancer cells in peritoneal washings from CRC patients after curative resection using multiple molecular markers, including cancer stem-like cells. Methods: A total of 170 CRC patients who had undergone curative surgery were studied. Peritoneal washings of the Douglas cavity were collected and used for cytology and molecular diagnosis. Real-time RT-PCR for carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and CD133 mRNA was performed to detect free cancer cells. Results: Molecular detection of CEA, CK20 and/or CD133 (CEA/CK20/CD133) mRNA of the peritoneal washings showed a significant correlation with lymph node metastasis and the tumor stage. The overall survival (OS) rates and peritoneal recurrence-free survival (PFS) rates in CEA/CK20/CD133 mRNA-positive patients were significantly lower than those of marker gene-negative patients. CD133/CEA/CK20 mRNAs in peritoneal washings were independent prognostic factors for OS and PFS. Conclusion: Molecular detection of free cancer cells using multimarkers, including cancer stem-like cells in peritoneal washings of post-curative surgery CRC patients, are useful in prognosis prediction.

A case of lung squamous cell carcinoma with metastases to the duodenum and small intestine.

Gastrointestinal metastasis of lung cancer is fairly rare, and metastasis to the duodenum is very uncommon. We report a case of duodenum and small intestine metastases of lung squamous cell carcinoma. The patient was a 66-year-old man. He was diagnosed with lung squamous cell carcinoma (T4N3M1 [mediastinum, cervical lymph node, and duodenum metastases], stage IV). He noted a sense of abdominal fullness on the evening of the day chemoradiotherapy was given, and emergency surgery was performed for suspected perforation of the digestive tract. Intraoperative findings included a tumor in the small intestine with a perforation at the tumor site; partial resection of the small intestine, including the tumor, was performed. Small intestine metastasis of lung cancer was diagnosed following histopathologic examination. When lung cancer patients complain of abdominal symptoms, it is important to consider gastrointestinal metastases in diagnosis and treatment.

Perforation of the Small Bowel Due to Metastasis From Tongue Cancer

Distant small bowel metastases from head and neck squamous cell carcinomas are extremely rare, and tongue cancer metastasizing to the small bowel has not been previously reported. We describe a 40-year-old male patient who underwent subtotal gross laryngectomy for squamous cell carcinoma of the tongue in February 2007 and then presented in November 2008 with severe abdominal pain. Abdominal computed tomography (CT) and X-rays revealed free air, suggesting intestinal perforation. Emergency surgery revealed a 10-mm perforation at the ileum and a palpable hard tumor at the perforation site. The ileum was resected, and pathologic findings showed squamous cell carcinoma at the perforation site, which was consistent with metastasis from tongue cancer.

Skin Metastasis From Sigmoid Colon Cancer

Skin metastases from visceral cancers are rare and the reported incidence from all visceral cancers is 1.4% to 10%. Skin metastases from colorectal cancers account for only 5% of metastatic skin cancers, among which scalp metastases are very rare. We describe a 53-year-old man with scalp metastasis derived from sigmoid colon cancer that was diagnosed and surgically resected in 2005. Metastatic lung tumors that developed thereafter were surgically resected and then chemotherapy was administered. However, metastatic brain tumors occurred in 2008, and these were treated by gamma-knife radiosurgery. Around the same time, a raised lesion that appeared on the scalp was diagnosed as skin metastasis and treated with best supportive care. Thereafter, the brain metastases continued to spread, and the patient died in October 2008.

Invasive micropapillary carcinoma of the ascending colon--a report of a case.

Micropapillary carcinoma (MC) has been recently recognized to be a rare but distinctive variant of adenocarcinoma. At present, only a limited number of colorectal MC cases have been reported. We present a case of MC of the ascending colon with distant metastasis. A 61-year-old female patient was hospitalized with a complaint of abdominal pain. A diagnostic work-up revealed cancer of the ascending colon with multiple lung metastases. The patient underwent a right hemicolectomy with lymph node dissection. A peritoneal nodule was observed in the abdominal cavity during surgery, and this nodule was also resected. The pathologic findings of the colon tumor revealed components of conventional tubular adenocarcinoma and micropapillary carcinoma. Lymph nodes and a peritoneal nodule revealed tubular adenocarcinoma. MC is a rare disease but has high malignant potential. In the present case the tumor was small in size, but the patient had a peritoneal and multiple lung metastases.

Severance of a Ventriculoperitoneal Shunt Catheter Implanted Between the Cerebral Ventricle and Peritoneal Cavity, Resulting in Protrusion From the Anus

One rare complication of a ventriculoperitoneal (VP) shunt is perforation of the gastrointestinal tract by the catheter. We report a case in which the catheter severed spontaneously inside the peritoneal cavity, creating a communication between the intestinal tract and the peritoneal cavity. The patient was a 41-year-old man who presented with a VP shunt catheter protruding from the anus. Computed tomography showed that the VP shunt catheter, which had been put in place 25 years earlier, had severed spontaneously. The distal end had then perforated and entered the intestinal tract. The patient was hospitalized and emergency surgery was performed to repair the intestinal tract perforation caused by the end of the VP shunt catheter. Laparotomy revealed that the catheter had perforated the sigmoid colon. The VP shunt catheter was removed, and the perforation in the intestinal tract was closed by suturing. The patient was discharged on postoperative day 20.

Primary Volvulus of the Small Intestine Exhibiting Chylous Ascites: A Case Report

BACKGROUND Primary volvulus of the small intestine associated with chylous ascites is very rare, with only four reported cases. In this paper, we report a new case of primary volvulus associated with chylous ascites. CASE PRESENTATION The patient was a 70-year-old man. After experiencing bloating and abdominal pain for several hours, he called an ambulance and underwent an emergency examination at our hospital. Abdominal distension, pressure pain, and rebound tenderness were observed throughout his entire abdomen. The patient had a history of hypertension for which he was receiving oral treatment. Abdominal contrast-enhanced computed tomography (CT) revealed an edematous change in the intestinal membrane and volvulus of the small intestine. As findings suggestive of ischemia were observed in part of the intestines, emergency surgery was performed on the day of admission. Open surgery revealed approximately 500 mL of chylous ascites in the abdominal cavity. The small intestine had twisted 180° in a counter-clockwise direction at the root of the superior mesenteric artery, and the mesentery appeared milky white with edematous changes extending 75 to 240 cm from the ligament of Treitz. There was no evidence of intestinal necrosis; therefore intestinal resection was not performed. The volvulus of the small intestine was corrected. Moreover, because there was no other underlying disease observed, surgery was completed. The ascites collected during surgery revealed high levels of triglycerides at 332 mg/dL, and chylous ascites was diagnosed. An abdominal CT performed on the third day after surgery showed an improvement in intestinal edema, and primary volvulus of the small intestine associated with chylous ascites was diagnosed. Postoperative progress was good, and the patient was discharged on hospital day 10.