Tomoaki Mizobe

Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer

Aims: 5-Fluorouracil (5-FU) is one of the most widely used anticancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation, and these include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). The aim of this study was to compare the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, there was a comparison of these expression levels between the primary tumour and the corresponding metastasis. Methods: Of 55 patients with colorectal cancer, 20 had no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry. Results: Of the six 5-FU-related enzymes, the numbers of patients with expression of dUTPase (54% versus 15%; p = 0.005), TK (26% versus 0%; p = 0.019) and DPD (17% versus 45%; p = 0.033) were significantly different in those with primary tumours with metastasis compared with those with non-metastasis, respectively. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly greater from primary to metastasis among the 35 patients with metastasis. By contrast, the expression of OPRT, TS and dUTPase was decreased in 6, 5 and 7 patients, respectively, in metastatic sites. Conclusions: From this comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumours and their corresponding metastatic tumour. It is suggested that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.

The MMP-9 expression determined the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines in stage II or III colorectal cancer

Background: The aim of this study was to determine any correlation between the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines and the matrix metalloproteinase 9 (MMP-9) expression in primary colorectal cancer tissues. Patients and Methods: The data on 307 patients with colorectal cancer at stage II or III, who underwent potentially curative resection with lymphadenectomy, were reviewed. Of these, 188 received postoperative administration of oral fluoropyrimidines such as UFT and 5′-DFUR (chemotherapy group), while the other 119 patients underwent surgery alone (surgery-alone group). Immunostaining for MMP-9 was performed using surgical specimens of all 307 primary tumors and 18 recurrent tumors. Results: Overall, MMP-9 was positively expressed in the primary tumor in 44% of patients. Multivariate analysis revealed that the MMP-9 expression was a worse prognostic factor with a second highest hazard ratio for recurrence. The disease-free survival rate in the chemotherapy group was significantly higher than that in the surgery-alone group. However, no significant difference in disease-free survival rate between the two groups was found in patients with a tumor positive for MMP-9. There was a strong positive correlation of MMP-9 expression between the primary tumors and the recurrent liver or lung tumors. Conclusions: The efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5′-DFUR may not be as great for patients with a tumor positive for MMP-9 having a greater risk to postoperative recurrence.

Challenges in staging systems for colorectal cancer: clinical significance of metastatic lymph node number in colorectal cancer and mesorectal extension in rectal cancer.

In many countries, treatment for cancer is performed based on staging systems in which the degree of cancer development is defined objectively. A common staging system is thus needed to compare outcomes. The staging system for colorectal cancer in Japan has been made to enhance consistency with the TNM classification, and the categorization of metastatic lymph nodes and depth of invasion have been revised in recent years. Although these are important factors that determine disease stage, relationships between each factor and recurrence have shown differing prognoses. In our retrospective study, the prognosis of a group with only one metastatic lymph node was significantly better compared to a group with ≧2 metastatic lymph nodes. In addition, rectal cancer with mesorectal extension >5 mm showed low relapse-free survival rates and high recurrence rates. The validity of staging systems should thus be inspected from various perspectives.

Bowel obstruction caused by an internal hernia that developed after laparoscopic subtotal colectomy: a case report

IntroductionLaparoscopic surgery is a minimally invasive approach with good treatment outcomes and is currently the standard surgery for colorectal cancer in Japan. Mesenteric closure is considered unnecessary in laparoscopic colorectal surgery because it can damage the bowel and blood vessels. However, an internal hernia may develop if the mesentery is not repaired.Case presentationWe report a case of internal hernia in a 61-year-old male of Japanese ethnicity. The patient had advanced sigmoid colon cancer, early-stage transverse colon cancer, and multiple adenomatous polyposis, and underwent laparoscopically-assisted subtotal colectomy. Bowel obstruction developed six days postoperatively and did not improve with conservative treatment. Abdominal computed tomography detected an internal hernia, prompting emergency surgery in which the ileum protruding into the mesenteric defect and an anastomotic stricture were detected. Reanastomosis, mesentery closure, and ileostomy were performed after hernia repair.ConclusionIn this case, open surgery was necessary due to bowel obstruction after laparoscopic colectomy. This outcome indicated that mesenteric closure should have been performed. Thus, the benefits of mesenteric closure require assessment in future cases.

Clinicopathological evaluation of anoxic mucosal injury in strangulation ileus

BackgroundIn patients with strangulation ileus, the severity of bowel ischemia is unpredictable before surgery. To consider a grading scale of anoxic damage, we evaluated the pathological findings and investigated predictive factors for bowel gangrene.MethodsWe assessed 49 patients with strangulation ileus who underwent a laparotomy between January 2004 and November 2012. Laboratory tests and the contrast computed tomography (CT) were evaluated before surgery. According to the degree of mucosal degeneration, we classified anoxic damages into the following 3 grades. Ggrade 1 shows mild mucosal degeneration with extended subepithelial space. Grade 2 shows moderate degeneration and mucosal deciduation with residual mucosa on the muscularis mucosae. Grade 3 shows severe degeneration and mucosal digestion with disintegration of lamina propria.ResultsResected bowel specimens were obtained from the 36 patients with severe ischemia, while the remaining 13 patients avoided bowel resection. The mucosal injury showed grade 1 in 11 cases, grade 2 in 10 cases, and grade 3 in 15 cases. The patients were divided into two groups. One group included grade 1 and non-resected patients (n = 24) while the other included grades 2 and 3 (n = 25). When comparing the clinical findings for these groups, elevated creatine kinase (P = 0.017), a low base excess (P = 0.021), and decreased bowel enhancement on the contrast CT (P = 0.001) were associated with severe mucosal injury.ConclusionIn strangulation ileus, anoxic mucosal injury progresses gradually after rapid spreading of bowel congestion. Before surgical intervention, creatine kinase, base excess, and bowel enhancement on the contrast CT could indicate the severity of anoxic damage. These biomarkers could be the predictor for bowel resection before surgery.

The Impact of Body Mass Index on Perioperative Outcomes After Laparoscopic Colorectal Surgery.

Laparoscopic colorectal surgery has gained increasing attention during the past 20 years. Surgeons today are more often confronted with obese patients. Therefore, it is timely to investigate the feasibility and safety of laparoscopic surgery for colorectal disease in obese patients. This study included 65 patients with colorectal disease who underwent laparoscopic surgery, between January 2009 and January 2014, at Kurume University Hospital. We divided the patients in this study into two groups based on their body mass index (BMI): <25 kg/m(2) (non-obese group) and ≥ 25 kg/m(2) (obese group). We assessed baseline characteristics and surgical outcomes, and these were compared between the non-obese group and the obese group. There were 53 patients in the non-obese group, and 12 patients in the obese group. There was no significant difference between the two groups of patients with regard to age, sex, co-morbidity, tumor location, tumor node metastasis (TNM) stage, tumor size and serum carcinoembryonic antigen (CEA) level. The duration of the operation was longer (by about 49 mins) for obese patients than non-obese patients. The conversion rate, amount of blood loss, number of lymph nodes resected, and duration of postoperative hospital insertion were each similar between the two groups. There was no significant difference between the two groups with regard to the overall incidence of postoperative complications; however, the incidence of incisional hernia tended to be more frequent in obese patients. There was no mortality in the two groups. Laparoscopic colorectal surgery is technically feasible and safe for obese patients. However, obesity is associated with longer duration and with higher risk of incisional hernia. Our findings suggest that BMI may not be an accurate estimate of visceral fat, and further studies may be useful for understanding the impact of obesity.

External sphincter resection for lower rectal and anal canal adenocarcinoma: achieving anal preservation with oncological and functional satisfaction

Intersphincteric resection (ISR) has recently been performed for very low rectal cancer, whereas abdominoperineal resection (APR) is typically reserved for cancers extremely close to the anal verge and/or when the depth of tumor invasion is suspected to involve the intersphincteric space. This is because impairment of anal function is considered unavoidable if the external sphincter (ES) is excised. We describe our technique of ISR with ES resection and discuss its outcomes. This surgical technique may offer major clinical advantages to selected patients and should be considered as an alternative to APR, although careful consideration of anal function is required.

Histopathological predictors for local recurrence in patients with T3 and T4 rectal cancers without preoperative chemoradiotherapy.

Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR.

Technical tips for intersphincteric resection: how to take out the rectum

Intersphincteric resection (ISR) is an ideal technique that preserves the anus, regardless of whether the internal anal sphincter is removed. However, it is difficult to dissect the anterior wall of the rectum from the adjacent organs. We herein describe a safe and useful ISR technique which draws out the rectum through the anus. The intersphincteric space (ISS) between the internal and external anal sphincter muscles was first transabdominally dissected. Next, the transanal dissection was advanced into the ISS bilaterally from the posterior side without dissecting the anterior wall of the anal canal, and the sigmoid colon and rectum were drawn out through the anus. Dissection between the anterior wall of the rectum and prostate/vagina could be easily performed under direct vision. This technique enables the dissection without any risk of a positive surgical margin or unexpected bleeding, and avoids injury to adjacent organs. This technique seems to be a safe and useful dissection technique for approaching the anterior wall of the anal canal.