Chihiro Kosugi

Early results of intersphincteric resection for patients with very low rectal cancer: An active approach to avoid a permanent colostomy

Purpose: Abdominoperineal resection has been the standard surgery for very low rectal cancer located within 5 cm of the anal verge. However, permanent colostomy exerts serious limitations on quality of life. The present study aimed to investigate curability and functional results of intersphincteric resection and additional partial external sphincteric resection for carcinoma of the anorectal junction. Methods: Thirty-five patients were prospectively studied from November 1999 to September 2002. All patients displayed adenocarcinoma (T3: n = 26; T2: n = 7; T1: n = 2) located between 0 and 2 cm above the dentate line. Abdominotransanal rectal resection with total mesorectal excision was performed in all patients (total intersphincteric resection: n = 14; subtotal intersphincteric resection: n = 5; additional partial external sphincteric resection: n = 6). All patients underwent diverting colostomy, which was closed at a median of six months postoperatively. Twenty patients received preoperative radiochemotherapy. Results: All patients had curative intent with microscopic safety margins (mean surgical cut end: 4 mm; mean distal cut end: 10 mm). No postoperative mortality was encountered. Morbidity was identified in 13 patients (perianastomotic abscess: n = 4; anastomotic leakage and fistula: n = 4; postoperative bleeding: n = 2; wound infection: n = 1; anastomotic stenosis: n = 1; anovaginal fistula: n = 1). One of these patients received a permanent colostomy. Five patients developed recurrence (liver: n = 1; lung: n = 2; local and lung: n = 1; abdominal wall: n = 1) during the median observation period (23 months). Two of these patients underwent curative resection of liver or lung metastases. Twenty-one patients have received stoma closure, and although continence was satisfactory in all, 5 displayed occasional minor soiling 12 months after stoma closure. Anal canal manometry demonstrated significant reduction in maximum resting pressure (median: 50 cmH2O at 12 months after stoma closure), but acceptable function results were obtained. Conclusion: Curability and anal function were achieved by means of intersphincteric resection without or with additional partial external sphincteric resection. These procedures can be recommended for low rectal cancer patients who are candidates for abdominoperineal resection.

Denervation of the neorectum as a potential cause of defecatory disorder following low anterior resection for rectal cancer

PURPOSEThe aim of this study was to determine whether denervation of the sigmoid colon during low anterior resection contributes to the postoperative motility characteristics of the neorectum and to the defecatory function of patients.METHODSSixty-seven patients who underwent either low or ultralow anterior resection for rectal cancer were evaluated. In accordance with the length of denervated neorectum, each patient was assigned to either the short-denervation or long-denervation group, determined by whether the inferior mesenteric artery was divided. Colonic propagated contraction was then measured by means of intraluminal pressure monitoring. Transit time was calculated with orally administered radiopaque markers.RESULTSPropagated contraction down to the neorectum was significantly less common in the long-denervation group (14/36) than in the short group (12/15, P < 0.05), whereas spastic minor contraction at the neorectum was significantly more common in the long-denervation group (21/36) than the in short group (3/15, P < 0.05). Colonic transit time below the sigmoid colon was significantly longer in long group (6.4 hours) than in the short group (3.4 hours, P < 0.01). Although motility disorder of the neorectum was correlated with clinical defecatory malfunctions, including multiple evacuations, urgency, and soiling, no significant correlation was noted between the length of the denervated neorectum and the defecatory disorders.CONCLUSIONSMotility of the neorectum following low anterior resection appears degraded by intraoperative maneuvers that cause denervation of the remnant sigmoid colon. Motility disorder of the neorectum, but not the length of the denervated neorectum causing the disorder, correlates well with several defecatory malfunctions. This finding suggests that postoperative defecatory disorder as a result of low anterior resection is caused by many factors in addition to denervation of the neorectum.

Antitumor effect of 1, 8-cineole against colon cancer

Several essential oils possess pharmacological effects. Among the various constituents of essential oils, 1, 8-cineole has been shown to possess pharmacological effects such as anti-bacterial and anti-inflammatory effects. The effect of 1, 8-cineole on human colorectal cancer cells, however, has not reported previously. In this study, we have investigated the anti-proliferative effect of 1, 8-cineole on human colon cancer cell lines HCT116 and RKO by WST-8 and BrdU assays. The cytotoxicity of 1, 8-cineole was investigated by LDH activity and TUNEL staining. The mechanism of apoptosis by 1, 8-cineole was determined by western blot analyses. In in vivo study, RKO cells were injected into the SCID mice and the effect of 1, 8-cineole was investigated. Specific induction of apoptosis, not necrosis, was observed in human colon cancer cell lines HCT116 and RKO by 1, 8-cineole. The treatment with 1, 8-cineole was associated with inactivation of survivin and Akt and activation of p38. These molecules induced cleaved PARP and caspase-3, finally causing apoptosis. In xenotransplanted SCID mice, the 1, 8-cineole group showed significantly inhibited tumor progression compared to the control group. These results indicated 1, 8-cineole suppressed human colorectal cancer proliferation by inducing apoptosis. Based on these studies 1, 8-cineole would be an effective strategy to treat colorectal cancer.

Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells

Fatty acid synthase is highly expressed in many types of human cancers. Cerulenin, a natural inhibitor of fatty acid synthase, induced apoptosis in the human colon cancer cell lines HCT116 and RKO. Oxaliplatin also induced cell death in these cell lines. Cerulenin treatment was associated with reduced levels of phosphorylated Akt, activation of p38 and induced caspase-3 cleavage and finally caused apoptosis. Oxaliplatin induced activation of the p53-p21 pathway and p38. In combination with cerulenin and oxaliplatin, activation of the p53-p21 pathway and p38 occurred in a smaller concentration and finally induced caspase-3 cleavage in a smaller concentration of cerulenin and oxaliplatin. In xenotransplanted SCID mice, the cerulenin + oxaliplatin group significantly inhibited tumor progression compared to the control, cerulenin and oxaliplatin groups. Based on these studies, inhibiting fatty acid synthase would be an effective strategy to treat unresectable colorectal cancer tumors in combination with oxaliplatin. Fatty acid synthase inhibitor would be one of the best counterparts of oxaliplatin, which reduces the dose and side-effects of oxaliplatin and would make it possible to endure the chemotherapy over a longer period.

Evaluation for transvaginal and transgastric NOTES cholecystectomy in human and animal natural orifice translumenal endoscopic surgery

BACKGROUND/PURPOSE Natural orifice translumenal endoscopic surgery (NOTES) is a novel concept using an endoscope via a translumenal access for abdominal surgery. This study was designed to evaluate the feasibility and technical aspects of NOTES cholecystectomy from our experience on humans and animals. METHODS NOTES cholecystectomies were performed in 12 animal experiments, including 8 pigs (6 by transgastric and 2 by transvaginal accesses) and 4 dogs (4 transvaginal accesses), and a human female cadaver. RESULTS The entire gallbladder could be removed under direct vision in all experiments. The average time was 60 min by transgastric and 40 min by transvaginal in animals. It was 87 min for human transvaginal cholecystectomy. In all animal and human procedures, there was no major complication concerning the operation. DISCUSSION The transvaginal route may be the easiest route for abdominal NOTES. Percutaneous endoscopic gastrostomy (PEG) allowed the safe performance of a controlled gastric perforation and shortened the time. The hybrid method allowed performance of a safe procedure and shortened the time. CONCLUSIONS Transvaginal and transgastric NOTES cholecystectomy is technically feasible and safe in both humans and animals. New instrumentation needs to be developed to perform a pure NOTES cholecystectomy without transabdominal assistance.

Carbon dioxide-enhanced virtual MDCT cholangiopancreatography

Background/PurposeWe investigated the feasibility of new carbon dioxide-enhanced virtual multidetector computed tomography (MDCT) cholangiopancreatography (CMCP) for intraluminal exploration in 73 patients with hepatobiliary and pancreatic disease.MethodsCMCP was performed via a percutaneous or transpapillary drainage tube, and, synchronously, intravenous contrast material was employed for virtual angiography; three-dimensional (3D) virtual reality was incorporated using OsiriX and Fovia applications. The capability of carbon dioxide to delineate the biliary and pancreatic system was evaluated.ResultsAll CMCPs showed complete technical success; complications including pancreatitis or pain never occurred. The incidences of visible third- and fourth-order biliary branches were 100 and 86.0%. The capability of carbon dioxide to pass an obstruction through an occluded hilar bile duct malignancy was 80.0%; it provided feasible information on additional bile duct segments. The full extent of the gallbladder was depicted in 72.7% of the studies. Minimum 2-mm lesions of biliary stones or gallbladder polyps were clearly detected. The main or second-order pancreatic ducts were visible in 100 and 83.3% of the studies, respectively. Carbon dioxide enabled the replacement of mucin and pancreatic juice and facilitated the detection of cystic lesions of intraductal papillary-mucinous neoplasm (IPMN) in 75.0% of the studies. We succeeded in achieving 3D spatial recognition of vascular structures in the cholangiopancreatic region, through the fusion of CMCP and 3DCT arteriography and venography in a single image scanning, and radiation time was decreased. This combined modality proved to be feasible for planning operations and for image-guided navigated surgery in the resection of a malignancy.ConclusionsTo our knowledge, this is the first report to demonstrate the diagnostic accuracy of carbon dioxide MDCT cholangiopancreatography and the use of this modality for depicting biliary, pancreatic, and fusion blood vessels simultaneously. Carbon dioxide possesses many advantages over conventional iodinated contrast agents, and it might replace more invasive diagnostic measures in the near future.

Evaluation of Postoperative Damage to Anal Sphincter/Levator Ani Muscles with Three-Dimensional Vector Manometry after Sphincter-Preserving Operation for Rectal Cancer

BACKGROUND The aim of this study was to examine correlations between pressure profile of the anal canal and postoperative defecatory disorder after sphincter-preserving operation (SPO) for rectal cancer. STUDY DESIGN Using three-dimensional vector manometry, pressure profile and length of the anal canal were evaluated more than 1 year after SPO according to operation method and degree of postoperative defecatory function in 53 patients with rectal cancer. RESULTS Compared with high anterior resection as a control, the anal canal was shorter in operations with a pelvic floor maneuver, namely, low anterior resection, ultra-low anterior resection, and intersphincteric resection. Patients with postoperative defecatory disorder showed significantly shorter anal canal length than patients with fair function. Length of the circular high-pressure zone (> or = 20 mmHg) < 20 mm in the resting state was a strong predictor of severe postoperative defecatory malfunction, with Wexner score> or =10. CONCLUSIONS Operative maneuvers at the pelvic floor during SPO for rectal cancer may damage anal sphincter or levator ani muscles. The circular high-pressure zone can be measured only by three-dimensional manometry and may offer a useful indicator of sphincter damage after SPO for rectal cancer.

Damage to anal sphincter/levator ani muscles caused by operative procedure in anal sphincter-preserving operation for rectal cancer.

BACKGROUND Details of postoperative damage to anal sphincter tonus following sphincter-preserving operation for rectal cancer remain unclear. METHODS Postoperative anal tonus was measured using 3-dimensional (3D) vector manometry in 56 patients. Anal length with pressure from any direction was defined as total length (TL). Length with circular pressure (LCP), which is only measurable using 3D manometry, was also evaluated. RESULTS In operations associated with low anastomosis, both TL and LCP at rest were significantly shortened when compared with control (high interior resection [HAR]). In particular, degraded LCP at rest was obvious. Anal lengths in squeezing state were preserved except in cases with intersphincteric resection (ISR). Postoperative incontinence score inversely correlated with functional anal length at rest. CONCLUSIONS Although the sphincter muscles are mechanically preserved, function of the internal sphincter and subsequent defecatory function can be degraded in cases with operative procedures including surgical maneuvers at the pelvic floor.

Serotonin (5-HT3) receptor antagonists for the reduction of symptoms of low anterior resection syndrome

Purpose Serotonin (5-hydroxytryptamine [5-HT])3 receptor antagonists are effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), in which exaggerated intestinal/colonic hypermotility is often observed. Recent studies have suggested that the motility disorder, especially spastic hypermotility, seen in the neorectum following sphincter-preserving operations for rectal cancer may be the basis of the postoperative defecatory malfunction seen in these patients. We investigated the efficacy of 5-HT3 receptor antagonists in patients suffering from severe low anterior resection syndrome. Patients and methods A total of 25 male patients with complaints of uncontrollable urgency or fecal incontinence following sphincter-preserving operations were enrolled in this study. Defecatory status, assessed on the basis of incontinence score (0–20), urgency grade (0–3), and number of toilet visits per day, was evaluated using a questionnaire before and 1 month after the administration of the 5-HT3 antagonist ramosetron. Results All the parameters assessed improved significantly after taking ramosetron for 1 month. The effect was more prominent in cases whose anastomotic line was lower, ie, inside the anal canal. Defecatory function was better in patients who commenced ramosetron therapy within 6 months postoperatively, as compared to those who were not prescribed ramosetron for more than 7 months postoperatively. Conclusion These results suggest that 5-HT3 antagonists are effective for the treatment of low anterior resection syndrome, as in diarrhea-predominant irritable bowel syndrome. The improvement in symptoms is not merely time dependent, but it is related to treatment with 5-HT3 antagonists.

Naso-esophageal extraluminal drainage for postoperative anastomotic leak after thoracic esophagectomy for patients with esophageal cancer

Postoperative anastomotic leaks and subsequent mediastinal abscess are serious complications. The purpose of this study was to assess the efficacy of naso-esophageal extraluminal drainage after thoracic esophagectomy with gastric conduit reconstruction using a posterior mediastinal route. About 50 of 365 patients (13.7%) with esophageal cancer and postoperative anastomotic leak after curative esophagectomy was investigated. Beginning in June 2009, naso-esophageal extraluminal drainage by inserting a naso-esophageal aspiration tube into the abscess cavity when percutaneous abscess drainage was introduced which was ineffective or technically impossible. Twenty-five patients underwent naso-esophageal extraluminal drainage concomitantly with enteral nutrition. Twenty-one (84%) patients had major leaks, one (4%) minor leak and three (12%) had endoscopically proven conduit necrosis. None of the naso-esophageal extraluminal drainage cases (100%) required reintervention or reoperation and all experienced complete cure (100%) during hospitalization. Endoscopic balloon dilatation was performed for four patients after discharge because of anastomotic stricture. Patients with leaks were divided into two groups: current group (n = 32), treated after June 2009, and preceding group (n = 18), treated prior to the introduction of naso-esophageal extraluminal drainage. Significantly more patients in the preceding group suffered respiratory failure (28% vs. 61%, p = 0.024), and higher reoperation rate (0% vs. 17%, p = 0.042) and hospital mortality (0% vs. 22%, p = 0.013). In the current group, 31 (97%) patients experienced complete cure during hospitalization. Naso-esophageal extraluminal drainage and concomitant enteral nutritional support are less invasive, and effective and powerful methods to treat even major leakage after esophagectomy. These methods may be an alternative management to improve mortality for patients with esophageal cancer.