Yuji Takakura

Single-port laparoscopic colectomy versus conventional laparoscopic colectomy for colon cancer: a comparison of surgical results

BackgroundSingle-port laparoscopic surgery is a new technique that leaves no visible scar. This new technique has generated strong interest among surgeons worldwide. However, single-port laparoscopic colon surgery has not yet been standardized. Our aim in this study was to evaluate the feasibility of single-port laparoscopic colectomy compared with conventional laparoscopic colectomy for colon cancer.MethodsWe conducted a case-matched, controlled study comparing single-port laparoscopic colectomy to conventional laparoscopic colectomy for right-sided colon cancer.ResultsA total of ten patients were included for the single-port laparoscopic colectomy (S-LAC) group and ten patients for the conventional laparoscopic colectomy (C-LAC) group. The length of the skin incision in the S-LAC group was significantly shorter than that of the C-LAC group.ConclusionOur early experiences indicated that S-LAC for right-sided colon cancer is a feasible and safe procedure and that S-LAC results in a better cosmetic outcome.

CDX2 Regulates Multidrug Resistance 1 Gene Expression in Malignant Intestinal Epithelium

The caudal-related homeobox transcription factor CDX2 has a key role in intestinal development and differentiation. CDX2 heterozygous mutant mice develop colonic polyps, and loss of CDX2 expression is seen in a subset of colon carcinomas in humans. Ectopic CDX2 expression in the stomach of transgenic mice promotes intestinal metaplasia, and CDX2 expression is frequently detected in intestinal metaplasia in the stomach and esophagus. We sought to define CDX2-regulated genes to enhance knowledge of CDX2 function. HT-29 colorectal cancer cells have minimal endogenous CDX2 expression, and HT-29 cells with ectopic CDX2 expression were generated. Microarray-based gene expression studies revealed that the Multidrug Resistance 1 (MDR1/P-glycoprotein/ABCB1) gene was activated by CDX2. Evidence that the MDR1 gene was a direct transcriptional target of CDX2 was obtained, including analyses with MDR1 reporter gene constructs and chromatin immunoprecipitation assays. RNA interference-mediated inhibition of CDX2 decreased endogenous MDR1 expression. In various colorectal cancer cell lines and human tissues, endogenous MDR1 expression was well correlated to CDX2 expression. Overexpression of CDX2 in HT-29 cells revealed increased resistance to the known substrate of MDR1, vincristine and paclitaxel, which was reversed by an MDR1 inhibitor, verapamil. These data indicate that CDX2 directly regulates MDR1 gene expression through binding to elements in the promoter region. Thus, CDX2 is probably important for basal expression of MDR1, regulating drug excretion and absorption in the lower gastrointestinal tract, as well as for multidrug resistance to chemotherapy reagent in CDX2-positive gastrointestinal cancers.

Short disease‐free interval is a significant risk factor for intrapulmonary recurrence after resection of pulmonary metastases in colorectal cancer

Objective  Surgical resection has been the first choice of treatment for resectable pulmonary metastases from colorectal cancer. However, early intrapulmonary recurrence is often observed and appropriate assessment of prognostic factors is controversial. The aim of this study was to define the factors affecting survival and intrapulmonary recurrence after surgical treatment of metastatic pulmonary tumours from colorectal cancer.

Retroperitoneal abscess complicated with necrotizing fasciitis of the thigh in a patient with sigmoid colon cancer

BackgroundNecrotizing fasciitis of the thigh due to the colon cancer, especially during chemotherepy, has not been previously reported.Case presentationA 67-year-old man admitted to the hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle. Multiple hepatic metastases were also found, and combination chemotherapy with irinotecan and S-1 was administered. Four months after the initiation of chemotherapy, the patient developed gait disturbance and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high C-reactive protein level. Computed tomography of the abdomen and pelvis showed gas and fluid collection in the retroperitoneum adjacent to the sigmoid colon cancer. The abscess was locally drained under computed tomographic guidance; however, the infection continued to spread and necrotizing fasciitis developed. Consequently, emergent debridement was performed. The patient recovered well, and the primary tumor was resected after remission of the local inflammation.ConclusionNecrotizing fasciitis of the thigh due to the spread of sigmoid colon cancer is unusual, but this fatal complication should be considered during chemotherapy for patients with unresectable colorectal cancer.

Adequate lymph node examination is essential to ensure the prognostic value of the lymph node ratio in patients with stage III colorectal cancer

PurposeThis study aimed to assess the prognostic value of the lymph node ratio (LNR), estimated by dividing the number of positive lymph nodes (LNs) by the number of LNs examined, for stage III colorectal cancer in comparison to the new tumor, nodes, and metastasis (TNM) system, and to evaluate the relationship between the number of LNs examined and the prognostic value of the LNR.MethodsWe retrospectively reviewed the clinicopathological data of a cohort of 266 patients with stage III colorectal cancer. We assessed the impact of LNR on the prediction of cancer recurrence in comparison to the TNM system, as well as the prognostic value of LNR in patients with a low LN count.ResultsIn multivariate analysis, the LNR was found to be an independent risk factor of cancer recurrence. The application of the LNR, in addition to the new TNM system, was more predictive of survival than the TNM system alone. A prognostic separation by LNR was observed in patients who had an adequate number of LNs examined, but not in patients with a low LN count.ConclusionsA stronger prognostic separation can be obtained by using the LNR together with the new TNM system. Adequate lymph node examination is important to ensure the prognostic value of LNR in patients with stage III colorectal cancer.

Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice

The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma—caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc+/flox, abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apcflox/flox and CDX2P9.5-G22Cre;Apcflox/flox) instability, respectively—were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apcflox/flox and CDX2P9.5-G22Cre;Apcflox/flox mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences in gastrointestinal commensal populations.

Malignant peripheral nerve sheath tumor arising from the greater omentum: Case report

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors that arise from a peripheral nerve or exhibit nerve sheath differentiation. Most of these tumors arise on the trunk, extremities, or head and neck regions; they are very rarely located in the abdominal cavity. The patient was a 71-year-old man who was referred to our hospital for a mass and pain in the right lower abdomen. Abdominal computed tomography revealed a large (9 × 9 cm), well-circumscribed, lobulated, heterogeneously enhanced mass in the pelvis. Exploratory laparotomy revealed a large mass in the greater omentum, and the tumor was completely excised. Histopathological analysis revealed that the tumor was composed of spindle cells with high mitotic activity. On staining the tumor, positive results were obtained for S-100 but negative results were obtained for c-kit, cluster of differentiation (CD)34, α-smooth muscle actin, and desmin. These findings strongly supported a diagnosis of MPNST primarily arising from the greater omentum. To the best of our knowledge, this is the first reported case of an MPNST arising from the greater omentum. In this report, we have described the case of a patient with an MPNST arising from the greater omentum and have discussed the clinical characteristics and management of MPNSTs.

External Validation of Two Nomograms for Predicting Patient Survival After Hepatic Resection for Metastatic Colorectal Cancer

BackgroundTwo nomograms are available for predicting patient survival after hepatic resection for metastatic colorectal cancer (CRC). However, they have not been externally validated using other databases, and so their universal applicability has not been established. We aimed to examine the validity of these nomograms for predicting patient survival after hepatic resection for metastatic CRC in different institutions.MethodsWe analyzed the cases of 113 patients who underwent hepatic resection for metastatic CRC at Hiroshima University Hospital between 1995 and 2006. In this patient set, we assessed the predictive value of the Kattan nomogram of the Memorial Sloan-Kettering Cancer Center (MSKCC) (United States) and the Kanemitsu nomogram from the Aichi Cancer Center (Japan). The concordance index was used as an accuracy measure for comparing these two nomograms. The predictive accuracy of these nomograms was compared with that of conventional predictive models.ResultsThe 3-, 5-, and 10-year overall survival rates in our cohort were 66.3%, 52.4%, and 42.7%, respectively. The concordance indexes of the pre- and postoperative Kanemitsu nomogram and that of the Kattan nomogram were 0.70, 0.69, and 0.68, respectively. These values were higher than those obtained using other models for hepatic metastatic CRC, including the clinical risk score of the MSKCC and the grading system of the Japanese Society for Cancer of the Colon and Rectum.ConclusionsThe high predictive accuracy of both nomograms shows that these predictive tools can be used in different institutions. Patient counseling and adjuvant therapy decision-making should benefit from use of these nomograms.

An elevated preoperative serum carbohydrate antigen 19-9 level is a significant predictor for peritoneal dissemination and poor survival in colorectal cancer

Many studies support the role of carcinoembryonic antigen (CEA) as a strong indicator of the status of colorectal cancer patients, but evidence for carbohydrate antigen 19‐9 (CA19‐9) is poor. For this reason the study aimed to evaluate the prognostic value of preoperative serum CA19‐9 levels in colorectal cancer patients.

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.