A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer.

BACKGROUND: The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior. METHODS: A national database, collated prospectively from 21 regional centres, detailed TEM treatment in 487 subjects with rectal cancer. Data were used to construct a predictive model of local recurrence after TEM using semiparametric survival analyses. The model was internally validated using measures of calibration and discrimination. RESULTS: Postoperative morbidity and mortality were 14.9 and 1.4 per cent respectively. The Cox regression model predicted local recurrence with a concordance index of 0.76 using age, depth of tumour invasion, tumour diameter, presence of lymphovascular invasion, poor differentiation and conversion to radical surgery after histopathological examination of the TEM specimen. CONCLUSION: Patient selection for TEM is frequently governed by fitness for radical surgery rather than suitable tumour biology. TEM can produce long-term outcomes similar to those published for radical total mesorectal excision surgery if applied to a select group of biologically favourable tumours. Conversion to radical surgery based on adverse TEM histopathology appears safe for p T1 and p T2 lesions.

Management of early rectal cancer.

BACKGROUND: Early rectal cancer (ERC) is adenocarcinoma that has invaded into, but not extended beyond, the submucosa of the rectum (that is a T1 tumour). Local excision is curative for low-risk ERCs but for high-risk cancers such management is controversial. METHODS: This review is based on published literature obtained by searching the PubMed and Cochrane databases, and the bibliographies of extracted articles. RESULTS AND CONCLUSION: ERC presents as a focus of malignancy within an adenoma, as a polyp, or as a small ulcerating adenocarcinoma. Preoperative staging relies on endorectal ultrasonography and magnetic resonance imaging. Pathological staging uses the Haggitt and Kikuchi classifications for adenocarcinoma in pedunculated and sessile polyps respectively. Lymph node metastases increase with the Kikuchi level, with a 1-3 per cent risk for submucosal layer (Sm) 1, 8 per cent for Sm2 and 23 per cent for Sm3 lesions. Low-risk ERCs may be treated endoscopically or by a transanal procedure. Transanal excision or transanal endoscopic microsurgery may be inadequate for high-risk ERCs and adjuvant chemoradiotherapy may be appropriate. There is a low rate of recurrence after local surgery for low-risk ERCs but this increases to up to 29 per cent for high-risk cancers.

The management and outcome of anastomotic leaks in colorectal surgery.

PURPOSE: Anastomotic leaks in colorectal surgery are associated with significant morbidity and mortality and may result in poor functional and oncological outcomes. Diagnostic difficulties may delay identification and appropriate management of leaks. The aim of this study was to look at the diagnosis, clinical management and outcomes of anastamotic leaks in our department. METHOD: A retrospective audit and case note review of all patients who underwent the formation of a colorectal anastomosis between January 1996 and December 2002 (n = 1421) was performed. An anastomotic leak was defined as sepsis identified to have arisen from an anastomosis that subsequently required surgery, radiological drainage or intravenous antibiotics. Forty-one patients (25 male, 16 female) with a median age of 60 years (range 7-89 years) were identified as having suffered an anastomotic leak. RESULTS: The median time to diagnosis of an anastomotic leak following surgery was 7 days (range 3-29). At re-operation, 21 patients (51%) underwent formation of a stoma, and any who required the anastomosis to be formally taken down have been left with a 'permanent' stoma. Currently only four of 12 patients (33%) who required a stoma for an anastomotic leak following anterior resection have undergone stoma reversal. Eleven of 16 patients (69%) who had received a stoma following another colorectal procedure had undergone stoma reversal. The mortality associated with an anastamotic leak in this series was 5% (n = 2). CONCLUSION: Although anastomotic leaks following colorectal surgery are associated with significant morbidity and stoma formation, early and aggressive management should result in a low overall mortality. If an anastomosis is taken down following an anastomotic leak after anterior resection, this will usually result in a 'permanent' stoma.

Surgical therapy of perianal Crohn's disease.

The surgical management of perianal Crohn's disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a 'bridge' to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn's disease.

Histopathological mimicry in mucosal prolapse.

Mucosal prolapse solitary rectal ulcer syndrome is a condition which has frequently confused both pathologists and surgeons alike. Despite its recognition in the nineteenth century, it continues to be a diagnostic challenge. The significance of correctly diagnosing this condition is that it avoids the morbidity and mortality associated with major surgery or the side-effects of long-term medical treatment. This review considers the histological features of mucosal prolapse and how it may mimic other pathological conditions.

Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates.

PURPOSE: This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone. METHODS: Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures. RESULTS: Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent). CONCLUSIONS: There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry.

Long-term follow-up of strictureplasty for Crohn's disease.

BACKGROUND: Strictureplasty is an effective means of alleviating obstructive Crohn's disease while conserving bowel length. The aim of this study was to establish long-term outcomes of strictureplasty. METHODS: Between 1978 and 2003, 479 strictureplasties were performed in 100 patients during 159 operations. Information on Crohn's disease, medical therapy, laboratory indices, surgical details, complication rates and outcomes was recorded. The primary endpoint was abdominal reoperation. RESULTS: Mean follow-up was 85.1 (range 0.2-240.9) months. The overall morbidity rate was 22.6 per cent, with septic complications in 11.3 per cent, obstruction in 4.4 per cent and gastrointestinal haemorrhage in 3.8 per cent. The 30-day mortality rate was 0.6 per cent and the procedure-related series mortality rate 3.0 per cent. Perioperative parenteral nutrition was the only marker for morbidity (P < 0.001). Reoperation rates were 52 per cent at a mean of 40.2 (range 0.2-205.8) months after a first, 56 per cent at 26.1 (range 3.5-63.5) months after a second, 86 per cent at 27.4 (range 1.4-74.5) months after a third, and 62.5 per cent at 25.9 (range 7.3-70.5) months following a fourth strictureplasty procedure. The major risk factor for reoperation was young age (P < 0.001). CONCLUSION: Long-term follow-up has confirmed the safety of strictureplasty in Crohn's disease. Morbidity is appreciable, although the surgical mortality rate is low. Reoperation rates are comparable following first and repeat strictureplasty procedures.

Cancer surveillance in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis are at a higher risk of developing colorectal cancer than those without the disease. Surveillance programmes are used routinely to detect dysplasia and cancer in patients with ulcerative colitis. However, such programmes are poorly effective. This article discusses possible improvements suggested by recent research. METHODS: Papers relating to cancer associated with ulcerative colitis and surveillance programmes to detect such cancer were identified using Medline searches. Further papers were identified from the reference lists of identified papers. RESULTS: The probability of cancer for all patients with ulcerative colitis regardless of disease extent was 2 per cent at 10 years, 8 per cent at 20 years and 18 per cent at 30 years; the overall prevalence of colorectal cancer in any patient was 3.7 per cent. Indications for colonoscopic surveillance are extensive disease for 8-10 years, especially in those with active inflammation, a family history of colorectal cancer and primary sclerosing cholangitis. Problems affecting surveillance include the diagnosis of dysplasia, difficulty in differentiating 'sporadic' adenomas from a dysplasia-associated lesion or mass, and decision making based on surveillance findings. Molecular genetic and endoscopic advances to alleviate these problems are discussed. CONCLUSION: Rates of detection of dysplasia can be improved by chromoendoscopy. Molecular genetics has the potential to identify patients most at risk of cancer and can differentiate between different types of lesion.

Long-term function after restorative proctocolectomy.

PURPOSE: Early functional outcome after restorative proctocolectomy and formation of an ileoanal pouch is known to be good, but there are minimal data on the long-term function of the pouch. The aim of this study was to look at the long-term functional outcome in patients who had undergone restorative proctocolectomy and formation of an ileoanal pouch. METHODS: A total of 151 consecutive patients (96 males, 55 females) who underwent ileoanal pouch surgery between April 1983 and May 1993 were identified. Functional outcomes from the previous 12 months were appraised by a standardized questionnaire. RESULTS: The median age at surgery was 31 years (range, 6-63 years), with a median follow-up of 142 months (range, 100-221 months). Eighteen patients have had their pouches excised, with another patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch failure. Altogether, 115 patients were available for follow-up, and 98 patients (85 percent) returned questionnaires. The median pouch-emptying frequency was five times (range, 1-17) during the day and one time (range, 0-6) at night. A total of 74 percent of patients had perfect continence during the day. Most of the patients had no life-style restrictions related to the pouch, and 98 percent of patients would recommend a pouch to others. CONCLUSIONS: Long-term functional outcome after ileoanal pouch surgery is good in most patients. For patients requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an excellent long-term option.

Postoperative leakage and abscess formation after colorectal surgery.

Anastomotic leaks following colorectal surgery may be divided into those which are clinically significant and those which are not. Leakage occurs in 3.4-6% of all colorectal cases. It is most commonly associated with rectal anastomoses, being clinically significant in 2.9-15.3% of cases. Mortality following a leak may be 6.0-39.3%. There is no evidence that preoperative bowel preparation reduces the rate and consequences of leaks. There is no evidence for the use of drains when an anastomosis has been made outside the pelvis, but pelvic drainage may be important after anterior resection. The use of covering stomas has not been shown to reduce leak rate but does mitigate the clinical effects of leaks. Prompt diagnosis and further laparotomy can reduce mortality following leakage. Intra-abdominal abscesses can in most cases be treated by radiologically guided drainage. Anastomotic leaks are the most common cause of anastomotic strictures and are also associated with increased rates of local recurrence of cancer.

Chronic anal fissure.

BACKGROUND: The treatment of chronic anal fissure has shifted in recent years from surgical to medical. METHODS: A Medline search of studies relevant to modern management of chronic anal fissure was undertaken. RESULTS: Traditional surgery that permanently weakens the internal sphincter is associated with a risk of incontinence. Medical therapies temporarily relax the internal sphincter and pose no such danger, but their limited efficacy has led to displacement rather than replacement of traditional surgery. Emerging medical therapies promise continued improvement and new sphincter-sparing surgery may render traditional surgery redundant. CONCLUSION: First-line use of medical therapy cures most chronic anal fissures cheaply and conveniently. The few non-responders can be targeted for sphincter assessment before traditional surgery. If the initial good results of new sphincter-sparing surgery are confirmed, it may be possible to avoid any risk of incontinence, while achieving high rates of fissure healing.

Mechanism of action of botulinum toxin on the internal anal sphincter.

BACKGROUND: Botulinum toxin is an effective treatment for anal fissure. Manometric studies support an apparent action of botulinum toxin on the internal anal sphincter (IAS). This aim of this study was to establish the underlying mechanism. METHODS: Porcine IAS strips were suspended in a superfusion organ bath and allowed to equilibrate. Electrical field stimulation (EFS) was applied with parameters that induced nitrergic relaxation followed by noradrenaline-mediated contraction. These responses were compared before and after addition of botulinum toxin. RESULTS: All strips developed myogenic tone, which was slightly increased following the addition of botulinum toxin. EFS-induced nitrergic relaxation was unaffected by toxin treatment. However, EFS-induced contraction was significantly reduced by toxin treatment. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, caused muscle strip contraction, which was blocked by guanethidine, implying the presence of sympathetic ganglia within the IAS. Botulinum toxin significantly attenuated DMPP-induced contraction. CONCLUSION: In the treatment of anal fissure the major effect of botulinum toxin on the IAS is blockade of sympathetic (noradrenaline mediated) neural output. This is probably a postganglionic action, involving a reduction in noradrenaline release at the neuromuscular junction. Botulinum toxin has no significant effect on nitrergic transmission, which is probably not vesicular in nature.

Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade.

PURPOSE: Preoperative long-course chemoradiotherapy is recommended for rectal carcinoma when there is concern that surgery alone may not be curative. Downstaging of the tumor can be measured as rectal cancer regression grade (1-3) and may be of importance when estimating the prognosis. The aim of this study was to look at the long-term results of tumor regression in patients receiving long-course chemotherapy before surgical resection of rectal cancer. METHODS: We reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinoma of the mid rectum or distal rectum found to be stage T3/4 between January 1995 and November 1999. Patients received 45 to 50 Gy irradiation in 2-Gy fractions and an infusion of 5-fluorouracil. Surgical specimens were assessed for rectal cancer regression grade. Patients were followed up routinely with clinical examination, computed tomography, and colonoscopy. RESULTS: Sixty-five patients with a mean age 65 (range, 32-83) years underwent chemoradiotherapy before surgical resection. Thirty patients (46 percent) were classified as rectal cancer regression Grade 1, with 9 patients (14 percent) having complete sterilization of the tumor. Fifty-three patients (82 percent) underwent a curative resection. Overall survival, with a median follow-up of 39 (range, 24-83) months, was 67 percent and was associated with tumor downstaging. The local recurrence rate was 5.8 percent in those patients who underwent a curative resection and was significantly lower with rectal cancer regression Grade 1 tumors (P = 0.03). Eight of nine patients (89 percent) whose tumor had been sterilized were alive and well with no recurrence of tumor at a median follow-up of 41 (range, 24-70) months. CONCLUSIONS: Preoperative chemoradiotherapy resulted in significant regression of tumor. Overall survival was high and was associated with downstaging of tumor. The local recurrence rate was significantly lower with rectal cancer regression Grade 1 tumors and was not seen in patients with sterilized tumors.

L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.

BACKGROUND: Topical phenylephrine has been shown to increase resting anal canal pressure in normal and incontinent individuals. However, high concentrations of gel (10-40 per cent) are required that may cause local side-effects. The aim of this study was to determine whether methoxamine, another alpha-1-adrenoceptor agonist, might be a more potent alternative to phenylephrine. METHODS: Porcine internal anal sphincter (IAS) tissue was cut into strips, suspended in a superfusion organ bath and allowed to equilibrate. Strips were subjected to each drug under test for 20 s, sufficient to obtain stable tone. Phenylephrine, methoxamine (1 : 1 : 1 : 1 ratio of its four isomers) and each of the individual isomers of methoxamine were evaluated in turn. RESULTS: In vitro, methoxamine racemate and phenylephrine were similarly potent in causing contraction of IAS strips (mean(s.e.m.) dose giving half maximal effect (EC(50)) at 74.7(16.5) versus 58.3(13.4) micro M respectively; P = 0.443). However, one of the methoxamine isomers, L-erythro-methoxamine (EC(50) 17.6(3.7) micro M), was significantly more potent than the other three isomers, methoxamine racemate and phenylephrine (P = 0.002). CONCLUSION: L-Erythro-methoxamine is four times more potent than phenylephrine and is a possible treatment for incontinence. Trials are under way to examine the efficacy of L-erythro-methoxamine in vivo.

Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system.

PURPOSE: Long-course preoperative radiotherapy has been recommended for rectal carcinoma when there is concern about the ability to perform a curative resection, for example, in larger tethered tumors or those sited anteriorly or near the anal sphincter. "Downstaging" of the tumor may occur, and this is of importance when estimating the prognosis and selecting postoperative therapy for patients. We studied the effects of preoperative chemoradiotherapy on the pathology of rectal cancer, and we propose a simplified measurement of tumor regression, the Rectal Cancer Regression Grade. METHODS: We have reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinomas of the mid or distal third of the rectum found to be Stage T3/4 on transrectal ultrasound or CT between January 1995 and December 1998. Patients received 45 to 50 Gy irradiation and an infusion of 5-fluorouracil. The surgical specimens were examined by one pathologist, and the Rectal Cancer Regression Grade was quantified. RESULTS: Forty-two patients, mean age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures (5 percent). Comparison of preoperative and pathologic staging revealed that the depth of invasion was downstaged in 17 patients (38 percent), and the status of involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in 36 patients (86 percent), with 7 patients (17 percent) having complete regression with absence of residual cancer cells. CONCLUSION: Significant tumor regression was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing a "good" responsiveness. We propose a modified pathologic staging system for irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a measurement of tumor regression. The utility of the proposed Rectal Cancer Regression Grade must be tested against long-term outcomes before its value in predicting prognosis and survival can be determined.

Evidence for separate disease phenotypes in intestinal Crohn's disease.

BACKGROUND: This study investigated the hypothesis that separate phenotypes of Crohn's disease exist which display differing patterns of recurrence with a tendency to preservation of phenotype between serial operations. METHODS: Some 483 abdominal operations (278 patients) were identified from a prospectively compiled database. Patterns of recurrence (reoperation) were analysed by Kaplan-Meier plots and log rank tests according to disease phenotype (perforated, stenosed or ulcerated). Serial operations were analysed by agreement of phenotype and microscopic features of disease using kappa statistics and correlation coefficients. RESULTS: There was no significant difference in recurrence according to disease phenotype (median reoperation-free survival time 43.0, 50.2 and 47.9 months for perforated, stenosed and ulcerated types respectively; log rank chi(2) = 3.5, P = 0.18). There was poor agreement in phenotype between serial operations (kappa = 0.22 for first/second operation and kappa= 0.15 for second/third operation) and no significant correlation between pathological features was identified (r between -0.19 and 0.48). CONCLUSION: No evidence was found for the existence of separate disease phenotypes with differing natural histories or underlying pathological characteristics.