Smoking is a major risk factor for anastomotic leak in patients undergoing low anterior resection.

AIM: To examine modifiable risk factors for anastomotic leak in patients undergoing low anterior resection. METHOD: In total 233 patients undergoing low anterior resection for benign and malignant disease over a 10-year period at a single surgical unit were identified from a prospective database. The relationships between anastomotic leak and 17 variables were examined, including patient demographics, operative technique, tumour pathology, preoperative physiological function and smoking status. RESULTS: The majority (91%) of operations were carried out for rectal cancers, and 24 procedures (10%) were performed with laparoscopic assistance. The overall anastomotic leak rate was 14% (33/233). Patients with anastomotic leak had higher 30-day mortality (6%vs 1%, P<0.05) and stayed significantly longer in hospital (median 23 vs 10 days, P<0.001). On multivariate analysis, current smokers (OR 3.68, 95% CI 1.38-9.82, P=0.009) and patients with evidence of metastatic malignant disease (OR 3.43, 95% CI 1.29-9.13, P=.013) were at increased risk of anastomotic leak. CONCLUSION: Smoking and the presence of metastatic disease are major risk factors for the development of anastomotic leak following low anterior resection.

Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study.

BACKGROUND: Post-operative ileus (POI) affects most patients undergoing abdominal surgery. AIM: To evaluate the effect of alvimopan, a peripherally acting mu-opioid receptor antagonist, on POI by negating the impact of opioids on gastrointestinal (GI) motility without affecting analgesia in patients outside North America. METHODS: Adult subjects undergoing open abdominal surgery (n = 911) randomly received oral alvimopan 6 or 12 mg, or placebo, 2 h before, and twice daily following surgery. Opioids were administered as intravenous patient-controlled analgesia (PCA) or bolus injection. Time to recovery of GI function was assessed principally using composite endpoints in subjects undergoing bowel resection (n = 738). RESULTS: A nonsignificant reduction in mean time to tolerate solid food and either first flatus or bowel movement (primary endpoint) was observed for both alvimopan 6 and 12 mg; 8.5 h (95% CI: 0.9, 16.0) and 4.8 h (95% CI: -3.2, 12.8), respectively. However, an exploratory post hoc analysis showed that alvimopan was more effective in the PCA (n = 317) group than in the non-PCA (n = 318) group. Alvimopan was well tolerated and did not reverse analgesia. CONCLUSION: Although the significant clinical effect of alvimopan on reducing POI observed in previous trials was not reproduced, this trial suggests potential benefit in bowel resection patients who received PCA.

Airborne gamma survey of the historic Sleisbeck mine area in the Northern Territory, Australia, and its use for site rehabilitation planning.

An airborne gamma-survey provided information about the extent of radioactive contamination around the historic Sleisbeck mine. Quickbird satellite data were acquired to relate airborne measurements to land cover features. Enhanced equivalent uranium (eU) levels were found to be confined to the mine and low grade waste rock dumps. The average terrestrial background radiation dose rate estimated from the airborne gamma survey data was 0.10-0.14 microGy h(-1) while the area around the mine exhibited a maximum of approximately 2.3 microGy h(-1), but measurements on the ground indicate that this maximum is exceeded in some localized areas. Rehabilitation of the site is likely to result in a threefold reduction in radiation doses to people accessing the area.

Fibre supplementation in addition to loperamide for faecal incontinence in adults: a randomized trial.

BACKGROUND AND AIMS: Many patients with faecal incontinence (FI) are prescribed a constipating agent concurrently with either fibre supplementation or a low-residue diet. Clinician opinion varies as to which initial approach is best. This study compared these treatments in routine clinical practice. DESIGN: Double-blind randomized cross-over trial. PARTICIPANTS: Patients referred for FI. INTERVENTION: Six weeks of low-residue diet, placebo fibre supplement and loperamide followed by 6 weeks of fibre supplement, neutral diet and loperamide or the reverse order. RESULTS: Sixty-three patients were randomized. At baseline the mean Faecal Incontinence Severity Index (FISI) was 31. After low-residue diet, placebo fibre supplement and loperamide the FISI was 18.4 (standard deviation, SD 13.2). After fibre supplementation and loperamide the FISI was 18.8 (SD 14.1). The mean difference between the treatment arms was not significant (-0.8; 95% CI: -4.9 to 3.3). There was also no difference between the treatments for the SF-36 and the Faecal Incontinence Quality of Life scale. There was marked variability in individual responses, some favouring more fibre and some less. CONCLUSIONS: This study provides evidence that treatment with more or less fibre in addition to loperamide has similar clinical effectiveness overall, however individual tailoring of treatment seems important to achieve the best outcome.

The impact of splenectomy on outcome after resection for colorectal cancer: a multicenter, nested, paired cohort study.

PURPOSE: This study was designed to determine whether incidental splenectomy for iatrogenic injury affects long-term cancer-specific survival in patients having resection of an adenocarcinoma of the sigmoid or rectum. METHODS: A retrospective case-matched review of patients undergoing surgery for colorectal cancer with incidental splenectomy between January 1, 1990 and December 31, 1999 was undertaken. Data were analysed for age, American Society of Anesthesiologists physical status, gender, disease stage, operation type, and outcome. These cases were matched with patients from the same center, of the same age and gender, with the same stage of disease and operation, who did not require a splenectomy at the time of their surgery. RESULTS: Fifty-five patients were identified who had an iatrogenic splenectomy. Matched gender, stage, and American Society of Anesthesiologists-matched controls were identified. Follow-up from time of surgery to death or last follow-up ranged from 2 to 205 (median, 43) months. A Kaplan-Meier survival analysis using the Cox proportional hazards model to define the statistical significance found a significant difference between the groups favoring those without splenectomy (hazard ratio, 1.8; 95 percent confidence interval (CI), 1-3.3; P=0.0399). Cancer-specific survival at five years was 70 vs. 47 percent and at ten years was 55 vs. 38 percent. DISCUSSION: Patients with colorectal cancer who had splenectomy as a result of iatrogenic damage of the spleen while undergoing resection of the sigmoid or rectum for adenocarcinoma had a significantly worse prognosis.

Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.

The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

Risk of dysplasia in long-term ileal pouches and pouches with chronic pouchitis.

BACKGROUND & AIMS: Recent reports have suggested the mucosa of an ileal reservoir could be at risk of neoplasia. Risk factors may include the age of the pouch, chronic pouchitis, and previous colonic neoplasia. This study examined a group of such patients to determine the risk of dysplasia. METHODS: From a cohort of 1221 patients with ileal pouches, 171 patients with possible risk factors were selected. Successful contact was made with 138 patients who were invited for endoscopy and multiple biopsies. Biopsy specimens were stained with H&E and p53, scored for inflammatory changes including villous atrophy, and analyzed by flow cytometry. RESULTS: One hundred six patients took part and fell into 1 or more of the following clinical categories: chronic pouchitis (n = 34), pelvic pouch for > or =12 years (n = 42); Kock pouch for > or =14 years (n = 29), and neoplasia in colectomy specimen (n = 11). Thirty-three patients had severe villous atrophy. One patient of 106 (95% confidence interval, 0.9% +/- 1.6%) with a long-standing pouch had low-grade dysplasia that was multifocal. DNA analysis by flow cytometry showed aneuploidy in this patient and 2 others. CONCLUSIONS: These data suggest that the development of dysplasia in ileal pouches performed for ulcerative colitis is probably a rare event within 15-20 years of pouch surgery.

Lagrangian chaos and correlated Lévy flights in a non-Beltrami flow: transient versus long-term transport.

Long-range transport is studied numerically in a time-independent, three-dimensional (3D) fluid flow composed of the superposition of two chains of alternating vortices, one horizontal and the other vertical. Tracers in this flow follow chaotic trajectories composed of correlated Lévy flights with varying velocities. Locations of the chaotic regimes in the flow are compared with recent theories of chaos in non-Beltrami 3D flows. Growth of the variance of a distribution of tracers is divided into transient and long-term regimes, each with different growth exponents.

Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis.

PURPOSE: The aim of this study was to establish the prevalence of adenomatous polyps in the ileal pouch of patients with familial adenomatous polyposis. METHOD: Forty-three patients who had an ileal pouch for familial adenomatous polyposis were invited to have a careful endoscopic examination of their pouch, including dye spraying. The number of polyps was recorded, and up to ten were biopsied. In addition, four random biopsy specimens were taken from the proximal and four from the distal pouch. RESULTS: Thirty-three patients with a median age of 36 (range, 14-63) years who had a pouch (5 Kock and 28 pelvic) for a median of 7 (range, 1-19) years accepted the invitation. Twenty-one patients (64 percent) had endoscopically identified polyps, the number of polyps ranging from 1 to 100 (median, 10) and varying in size from 1 to 3 mm. Fourteen patients (42 percent) had adenomatous polyps and 4 of these also had microadenomas on random biopsies. Nine of the 14 patients with adenomas also had lymphoid polyps. Seven patients had lymphoid polyps only and two of these patients had a microadenoma on random biopsy. Four of 12 patients with no visible polyps had microadenomas in their random biopsies. The presence of adenomatous polyps (Pearson's correlation; P < 0.01) increased with the age of the pouch. In total, 20 of 33 (60 percent) patients had adenomas and or microadenomas. CONCLUSION: Adenomatous polyps occur frequently in ileal pouches. These findings are of concern, and therefore, regular surveillance seems warranted until the natural history of these adenomatous polyps is determined.

Corticotropin-releasing hormone binding to the syncytiotrophoblast membranes.

The human placenta secretes large amounts of corticotropin-releasing hormone (CRH) which was thought to exert a paracrine action in the placenta. We have recently characterized high-affinity binding sites for CRH in the human placenta. However, our studies utilized whole placental membranes, which did not identify the site of binding of CRH in the plasma membrane. In this study we investigated the characteristics of CRH binding to purified mother-facing, brush border membranes (BBM) and fetus-facing, basal plasma membranes (BPM) of the syncytiotrophoblast. The two membranes were separated by a series of differential and density-gradient centrifugations. The purity of the membranes was determined by measuring alkaline phosphatase, as a marker of BBM and Na+/K+ATPase as a marker of BPM. Each membrane showed specific and high-affinity binding. Scatchard analysis revealed a high-affinity binding site for CRH with Kd of 1.0 +/- 0.15 and 1.3 +/- 0.176 for BBM and BPM, respectively. The maximal number of binding sites was significantly different (P < 0.01) in the two plasma membranes: Bmax of 79 +/- 6.4 fmol/mg protein for BBM and 23 +/- 3.9 fmol/mg protein for BPM. Both the mother-facing and fetus-facing membranes of the syncytiotrophoblast contain binding proteins for CRH, with significantly more binding sites on the mother-facing membranes. The functional consequences of CRH binding could be different for the two polar membranes due to differential localization of second messenger systems between the two membrane types. It is proposed that partial purification of BBM and BPM provides a better system to study CRH action in the placenta, than whole placental membrane preparations.

Quality of life is excellent after a pelvic pouch for colitis-associated neoplasia.

PURPOSE: Despite high patient satisfaction with a pelvic pouch, patients experience some bowel dysfunction. Patients whose indication for surgery is neoplasia may have near-normal preoperative bowel function. We hypothesized that these patients would be less accepting of a poorer functional status after surgery, reflected in a poorer measure of quality of life. METHOD: Sixteen patients who had dysplasia or cancer as the primary indication for surgery were compared with a matched control group whose indication for surgery was failed medical therapy. Quality of life was assessed using one disease-specific instrument, the Inflammatory Bowel Disease Questionnaire, two generic quality-of-life instruments, the Sickness Impact Profile and the Short Form 36, and two utility assessments. RESULTS: The groups were well matched with no significant differences in functional outcome. Quality-of-life scores were high in both groups and there were no significant differences in overall quality of life between the two groups using all five instruments. There was evidence of a response shift phenomenon in the failed medical therapy control group. CONCLUSION: Quality of life of patients who have a pelvic pouch for colitis-associated neoplasia is excellent and the same as that of patients who have a pouch for failure of medical therapy.

Occupational Exposure in Nuclear Medicine and PET.

Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for scanning in oncology in our center, a radiation dose survey was performed to determine the impact on staff exposure. Conventional nuclear medicine procedures such as gallium scan, bone scans, and sestamibi cardiac scans are used for comparative purposes.Procedure: Patients were measured using a hand-held radiation monitor (Victoreen 450-P) at various distances and times that replicate typical patient contact scenarios in the Diagnostic Imaging Department.Results: We present our findings from the survey and the implications these have on staff radiation exposure. The data suggest that emerging oncologic techniques such as PET, high dose gallium-67, and high dose Tl-201 do not represent a significantly greater occupational radiation hazard than conventional nuclear medicine procedures.

Laparostomy for severe intra-abdominal infection complicating colorectal disease.

PURPOSE: The aim of this study was to evaluate the use of laparostomy in the management of patients with severe intra-abdominal infection resulting from colorectal disease. METHODS: Seven patients, four with inflammatory bowel disease, two with colorectal carcinoma, and one with diverticular perforation, underwent laparostomy during a six-year period for postoperative, severe, intra-abdominal infection. RESULTS: The median age was 42 years, the mean Acute Physiology and Chronic Health Evaluation II score was 22.7, and the observed mortality was 28.6 percent (2/7 patients). In one patient the laparostomy was closed at 11 days; in all the others the wound was left to heal by granulation and contraction, and two of these later required reconstructive surgery. The median follow-up was three years and seven months. CONCLUSION: Laparostomy is an effective and practical method of managing patients with severe intra-abdominal infection as a result of colorectal disease.

Aneuploidy and columnar cuff surveillance after stapled ileal pouch-anal anastomosis in ulcerative colitis.

PURPOSE: A stapled pouch-anal anastomosis without mucosectomy is widely used in restorative proctocolectomy. Uncertainty exists about the longer-term outcome of retaining a columnar cuff of epithelium in the anal canal and about the need for surveillance of the columnar cuff. The aim of this article was to assess the ability to obtain biopsies of the columnar cuff, to assess the risk of dysplasia, and to search for the presence of aneuploidy as an early of marker of dysplasia in nondysplastic epithelium. METHOD: A total of 457 biopsy specimens were taken during 203 examinations of 113 patients. All biopsy specimens were stained with hematoxylin and eosin and examined by microscopy. One hundred thirty-two of these biopsy specimens from 67 patients were frozen and analyzed by flow cytometry for aneuploidy. RESULTS: Mean follow-up after pouch formation was 2.5 years, and the time after diagnosis of ulcerative colitis was 10.1 years. Successful columnar cuff biopsies were done on 93 percent of patients. There was no dysplasia. Two biopsy specimens from one patient had aneuploidy. CONCLUSION: To date, neoplastic change in the columnar cuff is rare. A selective policy of surveillance biopsies is recommended that includes patients greater than ten years after the diagnosis of ulcerative colitis and patients with dysplasia or cancer in their proctocolectomy specimen, but long-term follow-up data are needed.

"Cuffitis" and inflammatory changes in the columnar cuff, anal transitional zone, and ileal reservoir after stapled pouch-anal anastomosis.

PURPOSE: During the past eight to ten years most surgeons have adopted the double-stapled technique to accomplish the pouch-anal anastomosis in restorative proctocolectomy for ulcerative colitis. Little attention has been focused on the functional implications of retaining a segment of diseased columnar mucosa in the upper anal canal. The aim of this study was to investigate clinically significant inflammation in the columnar cuff. METHOD: In all, 113 patients were studied and 715 biopsies were performed during a 2.5-year period. Biopsy specimens were taken from two or three sites, including the columnar cuff, ileal pouch, and anal transitional zone. Acute and chronic inflammation was scored for biopsy specimens from all three sites and compared with endoscopic assessment and pouch function. RESULTS: In the columnar cuff acute histologic inflammation was found in 13 percent of patients, and in 9 percent this was symptomatic during follow-up and was accompanied by evidence of endoscopic inflammation. Most patients had mild inflammation in the cuff that persisted over time. Inflammation in the pouch, pouch frequency, and anastomotic height were not related to columnar cuff inflammation. CONCLUSIONS: Cuffitis is a cause of pouch dysfunction after a double-stapled restorative proctocolectomy. We propose a triad of diagnostic criteria, including symptoms and endoscopic and histologic inflammation.

Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner.

Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) is an accurate technique for staging and therapeutic monitoring in oncology. We evaluated our use of FDG PET in an oncology centre after our first 2500 studies, and summarise our experience of PET for the major referral indications. Optimised for clinical service, PET offers lower scanning costs and therefore improved cost-effectiveness.

A new look at the anal transitional zone with reference to restorative proctocolectomy and the columnar cuff.

BACKGROUND: The anal transitional zone (ATZ) is of interest in relation to anorectal function and its fate during the operation of restorative proctocolectomy. There are only a few studies describing the anatomy of this structure. This study applied new techniques to quantify the ATZ in normal and inflammatory bowel disease states. METHODS: The epithelial linings of 28 anal canals were analysed by two techniques: whole-mount Alcian blue staining and a new method of creating a computer map of the histological findings based on longitudinal sections taken every 3 mm. The Alcian blue pictures and the histology maps were measured and compared using image analysis software. RESULTS: The ATZ usually commences just above the dentate line, which is situated a median of 1.05 cm above the lower border of the internal sphincter. The median length of the ATZ measured from computer maps of the histology was 0.45 cm. This was significantly smaller than the 0.73 cm obtained by the Alcian blue technique, which overestimates the length of the ATZ. The amount of columnar epithelium in the ATZ is very small. The median lowest point of columnar epithelium in the anal canal was 1.1 cm above the lower border of the internal sphincter. CONCLUSION: The ATZ is only half the length described previously. After double-stapled restorative proctocolectomy there is a 1.5-2.0-cm cuff of diseased columnar epithelium remaining in the upper anal canal above the ATZ. This is suitably termed the 'columnar cuff' and is an important consideration in long-term follow-up.

The significance of donor leg distal runoff in femorofemoral bypass grafting.

BACKGROUND: The aim of this study is to determine if femorofemoral bypass grafting is an effective operation for unilateral iliac occlusive disease, and to assess for factors that may predict a poorer outcome. A retrospective review was conducted of cases identified from a prospective audit database. METHODS: Information was obtained from the clinical notes of 97 patients who had 100 femorofemoral bypass graft operations. All living patients were invited for assessment which included colour duplex sonography of the graft and measurement of the ankle brachial index. RESULTS: Using life-table analysis, the five-year graft secondary patency for claudicants was 79% and for those with critical ischaemia 78%. Five-year survival for claudicants was 65% and for those with critical ischaemia, 38%. Poor distal runoff in the infrapopliteal arteries of the donor limb adversely affected graft patency. Graft survival was not affected by the indication for operation, by donor or recipient superficial femoral artery patency, or by the need for endarterectomy, pre-operative angioplasty or the graft material. CONCLUSIONS: Femorofemoral bypass grafting is the procedure of choice for all patients who require surgical intervention for unilateral iliac occlusion and donor limb distal runoff may be an important determinant of graft patency.