A sprayable hydrogel adhesion barrier facilitates closure of defunctioning loop ileostomy: a randomized trial.

PURPOSE: Closure of defunctioning loop ileostomy often is associated with division of complex peristomal adhesions through a parastomal incision with limited exposure. The goal was to determine whether sprayable hydrogel adhesion barrier (SprayGel) will reduce peristomal adhesions and facilitate closure of ileostomy. METHODS: Patients undergoing closure of loop ileostomy were randomized to have hydrogel adhesion barrier sprayed around both limbs of ileostomy for 20 cm (SprayGel group, n = 19), or to control without adhesion barrier (control group, n = 21). Ileostomy was reversed at ten weeks after construction. Extent of peristomal adhesions was scored in blinded manner (each quadrant, range, 1-3: 3 = most severe; total, range, 4-12: 12 = most severe). RESULTS: Use of adhesion barrier was associated with significant reduction in overall adhesion scores (mean, 6.11 vs. 9.67; P < 0.0005), four-quadrant adhesion scores (Quadrant A: 1.68 vs. 2.52, P = 0.002; Quadrant B: 1.42 vs. 2.33, P < 0.0005; Quadrant C: 1.42 vs. 2.24, P < 0.0005; Quadrant D: 1.58 vs. 2.48, P = 0.002), and proportion of patients with dense (scores > or = 8) adhesions (0.11 vs. 0.71; P < 0.0005). Time taken to mobilize (16.53 vs. 21.67 minutes; P = 0.008) and close ileostomy (35.37 vs. 41.90 minutes; P = 0.008) was significantly reduced. Postoperative complications were comparable. CONCLUSIONS: A sprayable hydrogel adhesion barrier placed around the limbs of a defunctioning loop ileostomy reduced peristomal adhesions and might facilitate closure of ileostomy.

Sacral nerve stimulation for fecal incontinence: external anal sphincter defect vs. intact anal sphincter.

PURPOSE: This prospective study was designed to assess the effectiveness of sacral nerve stimulation for fecal incontinence in patients with external anal sphincter defect and to evaluate its efficacy regarding presence and size of sphincter defect. METHODS: Fifty-three consecutive patients who underwent sacral nerve stimulation for fecal incontinence were divided into two groups: external anal sphincter defect group (n = 21) vs. intact sphincter group (n = 32). Follow-up was performed at 3, 6, and 12 months with anorectal physiology, Wexner's score, bowel diary, and quality of life questionnaires. RESULTS: The external anal sphincter defect group (defect <90 degrees:defect 90 degrees-120 degrees = 11:10) and intact sphincter group were comparable with regard to age (mean, 63 vs. 63.6) and sex. Incidence of internal anal sphincter defect and pudendal neuropathy was similar. All 53 patients benefited from sacral nerve stimulation. Weekly incontinent episodes decreased from 13.8 to 5 (P < 0.0001) for patients with external anal sphincter defects and from 6.7 to 2 (P = 0.001) for patients with intact sphincter at 12-month follow-up. Quality of life scores improved in both groups (P < 0.0125). There was no significant difference in improvement in functional outcomes after sacral nerve stimulation between patients with or without external anal sphincter defects. Clinical benefit of sacral nerve stimulation was similar among patients with external anal sphincter defects, irrespective of its size. Presence of pudendal neuropathy did not affect outcome of neurostimulation. CONCLUSIONS: Sacral nerve stimulation for fecal incontinence is as effective in patients with external anal sphincter defects as those with intact sphincter and the result is similar for defect size up to 120 degrees of circumference.

Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal incontinence: a randomized, controlled study.

PURPOSE: This randomized study was designed to compare the effect of sacral neuromodulation with optimal medical therapy in patients with severe fecal incontinence. METHODS: Patients (aged 39-86 years) with severe fecal incontinence were randomized to have sacral nerve stimulation (SNS group; n = 60) or best supportive therapy (control; n = 60), which consisted of pelvic floor exercises, bulking agent, and dietary manipulation. Full assessment included endoanal ultrasound, anorectal physiology, two-week bowel diary, and fecal incontinence quality of life index. The follow-up duration was 12 months. RESULTS: The sacral nerve stimulation group was similar to the control group with regard to gender (F:M = 11:1 vs. 14:1) and age (mean, 63.9 vs. 63 years). The incidence of a defect of < or = 120 degrees of the external anal sphincter and pudendal neuropathy was similar between the groups. Trial screening improved incontinent episodes by more than 50 percent in 54 patients (90 percent). Full-stage sacral nerve stimulation was performed in 53 of these 54 "successful" patients. There were no septic complications. With sacral nerve stimulation, mean incontinent episodes per week decreased from 9.5 to 3.1 (P < 0.0001) and mean incontinent days per week from 3.3 to 1 (P < 0.0001). Perfect continence was accomplished in 25 patients (47.2 percent). In the sacral nerve stimulation group, there was a significant (P < 0.0001) improvement in fecal incontinence quality of life index in all four domains. By contrast, there was no significant improvement in fecal continence and the fecal incontinence quality of life scores in the control group. CONCLUSIONS: Sacral neuromodulation significantly improved the outcome in patients with severe fecal incontinence compared with the control group undergoing optimal medical therapy.

Preoperative loco-regional imaging in rectal cancer.

Preoperative staging of rectal cancer can influence the choice of surgery and the use of neoadjuvant therapy. This review evaluates the use of endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) in the local staging of rectal cancer. Staging for distant metastases is beyond the scope of this review. A MEDLINE search for published work in English between 1984-2004 was carried out by entering the key words of ERUS, MRI and preoperative imaging and rectal cancer. Initially, 867 articles were retrieved. Abstracts were reviewed and papers selected according to the inclusion criteria of a minimum of 50 patients and papers published in English. Papers focusing on preoperative chemoradiotherapy and distal metastases were excluded. Thirty-one papers were included in the systematic review. The examination techniques and images obtained are discussed and the respective accuracy is reviewed. ERUS and MRI have complementary roles in the assessment of tumour depth. Ultrasound has an overall accuracy of 82% (T1, 2, 40-100%; T3, 4, 25-100%) and is particularly useful for early localized rectal cancers. MRI has an accuracy of 76% (T1, 2, 29-80%; T3, 4, 0-100%) and is useful in more advanced disease by providing clearer definition of the mesorectum and mesorectal fascia. Both methods have similar accuracy in the assessment of nodal metastases. Ultrasound is more operator dependent and accuracies improve with experience, but it is more portable and accessible than MRI. Improvements in technology and increased operator experience have led to more accurate preoperative staging. ERUS and MRI are complementary and are most accurate for early localized cancers and more advanced cancers, respectively.

Proteomic analysis of colorectal cancer: discovering novel biomarkers.

Colorectal cancer is one of the most common cancers in the Western world. When detected at an early stage, the majority of cancers can be cured with current treatment modalities. However, most cancers present at an intermediate stage. The discovery of sensitive and specific biomarkers has the potential to improve preclinical diagnosis of primary and recurrent colorectal cancer, and holds the promise of prognostic and therapeutic application. Current biomarkers such as carcinoembryonic antigen lack sensitivity and specificity for general population screening. This review aims to highlight the role of current proteomic technologies in the discovery and validation of potential biomarkers with a view to translation to the clinic.

Preoperative chemotherapy and radiotherapy for locally advanced rectal cancer.

BACKGROUND: The adjuvant treatment of rectal cancer is a rapidly evolving field. The standard approach is a combination of chemotherapy and radiotherapy, with the optimal treatment combination and sequencing yet to be determined. Here, we report our early experience of preoperative chemotherapy and radiotherapy (CRT) in locally advanced rectal cancer at Radiation Oncology Victoria to determine its efficacy and the rate of sphincter preservation. METHODS: Sixty-nine patients (46 men and 23 women) with locally advanced rectal cancer (T3-4 or N1) were treated with preoperative CRT followed by surgical resection of disease. Chemotherapy consisted of either bolus or continuous venous infusion of 5-fluorouracil (5-FU). Radiotherapy to a dose of 45 Gy was delivered to the pelvis followed by a boost of 5.4-14.4 Gy in the majority of patients. Surgical resection was carried out 4-8 weeks following completion of preoperative CRT. Univariate and multivariate analyses were performed to examine variables that may influence local recurrence and overall survival rates. RESULTS: All patients underwent a complete macroscopic resection, including the three patients that had unrecognized distant metastases discovered at the time of operation. Only two patients had microscopic residual disease. Sphincter preservation was achieved in 16 of 25 patients who were thought to require an abdominoperineal resection. Tumour and/or nodal downstaging were achieved in 47 patients (68%), with a pathological complete response in 12 (17%). At a median follow up of 29 months post-surgery, five patients (7.2%) have developed a local recurrence. Overall 21 patients (30%) have progressed and 12 (18%) have died. Treatment-related toxicity was acceptable and there was no treatment-related mortality. There was no significant relationship found between the pathological response to treatment and any clinical endpoint. CONCLUSIONS: Our results confirm the high response rates and acceptable toxicity of preoperative treatment. Further studies are required to better define the impact of preoperative chemotherapy and radiotherapy on long-term outcomes.

Intermediate conductance potassium (IK) channels occur in human enteric neurons.

IK channels, which had been previously found in hemopoetically derived cells (including erythrocytes and lymphocytes) and epithelial cells, where they regulate proliferation, cell volume regulation and secretion, have only recently been discovered in neurons, where they had previously been claimed not to occur. Based on immunohistochemical detection of IK channel-like immunoreactivity, it has been reported that IK channel expression in enteric neurons is suppressed in Crohn's disease. In the present work we have investigated whether authentic IK channels are expressed by enteric neurons. Human and mouse tissue was investigated by immunohistochemistry, Western blot and RT-PCR. Immunohistochemical studies revealed IK channel-like immunoreactivity in large myenteric neurons, but not in other cell types in the external muscle layers. Many of these nerve cells had calbindin immunoreactivity. Western blots from the external muscle revealed an immunoreactive band at the molecular weight of the IK channel. Using RT-PCR, we detected a transcript corresponding to the IK channel gene in extracts from the ganglion containing layer. The sequence obtained from the RT-PCR product was identical to that previously published for the IK channel. We conclude that IK channels are expressed by human enteric neurons, including large smooth surfaced neurons that are possibly the human equivalent of the Dogiel type II neurons that express these channels in small mammals.

Endoanal and endorectal ultrasound: applications in colorectal surgery.

Endoanal and endorectal ultrasound have an important role in colorectal surgery. They can be applied in the management of faecal incontinence, rectal tumours and inflammatory perianal conditions. In faecal incontinence, anal ultrasound will confirm the presence or absence of sphincter defects. This will direct any operative intervention such as direct sphincter repair. Ultrasound in rectal cancer allows staging of the tumour by assessing the depth of invasion through the bowel wall and involvement of mesenteric nodes. Such staging might influence the choice of operation and determine which patients might benefit from preoperative chemotherapy and radiotherapy. Ultrasound has a particular role in recurrent and complex anal fistula and perianal sepsis. Preoperative and perioperative planning with accurate delineation of fistula tracts, extensions and sphincter involvement might help prevent recurrence and impaired continence from sphincter damage after surgery. Correct interpretation of ultrasound images requires training and experience so that the results can be properly correlated with the clinical situation.

Sacral nerve stimulation: an emerging treatment for faecal incontinence.

Faecal incontinence is common, distressing to the patient and socially incapacitating. The treatment options depend on the severity and aetiology of incontinence. For mild cases of faecal incontinence, medical management and pelvic floor physiotherapy may be adequate. For more severe cases, surgery is often required. Patients who have a distinct sphincter defect are amenable to surgical repair. In many cases, there is a combination of diffuse structural damage of the anal sphincters with pudendal neuropathy. Conventional surgical repairs have a modest degree of success and the results tend to deteriorate with time. Neosphincter procedures such as artificial bowel sphincter and dynamic graciloplasty are potentially morbid and technically complex. Sacral nerve stimulation is innovative and has had a medium-term success with improvement of quality of life in over 80% of patients treated for faecal incontinence. These results are superior to other techniques in treating patients with severe refractory faecal incontinence, where current maximal therapy has failed. The technique is unique because there is a screening phase, which has a high predictive value. It is also associated with minimal complications that are usually minor. However, most published reports of sacral nerve stimulation for treatment of faecal incontinence were case studies and methods of assessing outcome were variable. Criteria for patient selection are evolving and are yet to be defined. The present paper critically reviews the publications to date on sacral nerve stimulation for treatment of faecal incontinence. This will form the basis for future evaluation of this emerging treatment of severe, intractable faecal incontinence. Randomized clinical trials like that of the Melbourne trial will further clarify the role and indications of sacral nerve stimulation for faecal incontinence.

Anatomy of the pudendal nerve and its terminal branches: a cadaver study.

BACKGROUND: This study documents the anatomy of the pudendal nerve, which has a major role in maintaining faecal continence. Unexpected faecal incontinence can develop following perineal surgery even when the anal sphincters are not damaged. In addition, injury to the pudendal nerve might be encountered during pelvic procedures such as a sacrospinous colpopexy. METHODS: An anatomical study on 28 cadavers was conducted to examine the course of the pudendal nerve and its branches in the perineum. RESULTS: In five of the 28 cadavers dissected (four male, one female), a nerve plexus was found within the ischiorectal fossa in close proximity to the anal sphincters. The plexus received contributions from interconnecting branches of the inferior rectal and perineal nerves to innervate the external anal sphincter. In 11 of the 28 cadavers (five female, six male) an additional nerve arose from the medial aspect of the pudendal nerve at the level of the sacrotuberous and sacrospinous ligaments. This nerve continued distally and gave several branches to the perineum and the levator ani muscle. CONCLUSION: A sound knowledge of the anatomical variations of the pudendal nerve and its branches is essential for all surgeons operating in the perineal region.

How could management of rectoceles be optimized?

A posterior vaginal wall prolapse, also known as a rectocele, is a common condition and is an outpouching of the posterior vaginal wall and anterior rectal wall into the lumen of the vagina.1-5 Although more common in parous women, rectoceles of over 1 cm in size have been demonstrated in over 40% of nulliparous women. As rectoceles may be asymptomatic, their true prevalence is not clear. Many women with rectoceles present to their gynaecologist who may not ascertain any anorectal symptoms or perform a rectal examination. Conversely, colorectal surgeons often disregard a vaginal examination.6 Conventionally, gynaecologists have managed rectoceles, but increasingly colorectal surgeons are involved because of the prevalence of anorectal symptoms. There are many surgical techniques for the management of a symptomatic rectocele. There is, however, little data to suggest which is the most effective technique, or whether specific techniques are more appropriate in certain circumstances.7

Carcinoma of the anal canal: a local experience and review of the literature.

BACKGROUND: Through the 1970s patients presenting with anal canal carcinoma were managed with a surgical approach--abdomino-perineal resection. Since then, the pioneering work of Nigro et al. and a series of large clinical trials have clearly demonstrated that combined chemotherapy and radiotherapy result in greater local control, colostomy-free survival and increase in overall patient survival. The aim of the present study is to determine how widely the combined modality approach has been adopted in routine clinical practice and what outcomes are achieved in this setting. METHODS: All patients with anal cancer treated at three tertiary referral centres over an 11-year period (1991-2001) were identified. Data were collected by a retrospective record review. RESULTS: Our search identified a total of 50 patients: 22 men and 28 women, with a median age of 62 years. Four patients had metastatic disease diagnosed at presentation. Nine patients (18%) were at least 75 years of age and three were known to be HIV positive. Median potential follow up is 52 months. Of the 46 patients treated for cure, 38 received a combination of chemotherapy and radiation, with 79% achieving a complete response. Efficacy was maintained in treated elderly patients (> or =75 years). The 5-year survival of the 38 patients with local or locoregional disease who received combined chemoradiation modality was 63%. CONCLUSIONS: Overall this series demonstrates that combined chemotherapy and radiotherapy has been adopted as standard treatment with outcome data similar to those reported in the randomized clinical trials. Where possible elderly patients should receive combined modality therapy.

Colonic epithelial atrophy induced by a fibre-free diet in rats is reversed by minimal amounts of luminal butyrate, but only in the short term.

BACKGROUND: Luminal butyrate may be trophic to the colonic epithelium, but this effect is poorly characterized. The aim of the present study was to define the dose-response, time-course, site-specificity and the dependence on background diet of the effects of butyrate on epithelial proliferation in normal distal colon, using an in vivo rat model of colonic substrate delivery. METHODS: Male Sprague-Dawley rats, maintained on a fibre-free diet, had butyrate infused twice daily into the colonic lumen via polyethylene tubes placed at laparotomy. Varying dose levels (0-80 micro mol/d; 4 d), site (caecal vs distal colonic), duration of infusions (1-5 weeks; 80 micro mol/d), or dietary fibre intake were investigated. Epithelial proliferative indices were assessed stathmokinetically. RESULTS: Four-day infusions of butyrate led to a progressive trophic effect (cells/crypt column increased from 37.9 +/- 1.6 at 0 micro mol/d to 44.7 +/- 1.2 at 80 micro mol/d) on fibre-deprived colonic mucosa, related linearly to the daily butyrate dose (P < 0.001, linear regression). This effect was mediated by increases in the number and proportion of mitoses, related to the square of the butyrate dose (P < 0.001 in each case, polynomial regression). Butyrate (80 micro mol/d) was associated with significantly higher cellularity (59.9 +/- 1.4) and mitotic activity (4.9 +/- 0.6) per crypt column compared to vehicle controls (50.3 +/- 1.6 and 0.9 +/- 0.2, respectively; P < 0.05, t-tests), at 1 and 3 weeks, but not at 5 weeks. Butyrate had similar effects on distal colonic crypt cellularity (62.0 +/- 1.5) when delivered caecally, but in rats fed a fibre-containing diet, colonic crypt cellularity (55.3 +/- 3.2) was similar to baseline (59.6 +/- 1.9). CONCLUSIONS: Trophic effects of butyrate are concentration-dependent and occur at low doses in the short term, but are not sustained over longer periods. They are seen only in a fibre-deprived state and appear to be independent of the site of administration.

How safe is adjuvant chemotherapy and radiotherapy for rectal cancer?

Over the last three decades, a series of clinical trials have led to the use of adjuvant pelvic radiotherapy and chemotherapy in high-risk (T3-4 or N1) rectal cancer. There is a need to improve patient selection in order to identify the group most at risk for recurrent disease. The toxicity of adjuvant therapy should be factored into this consideration. The optimal sequencing of adjuvant therapy before or after surgery, the use of short- or long-course radiotherapy, and the utility of concurrent chemotherapy is currently being examined in randomized controlled trials (RCTs). The aim of this report was to review the morbidity and mortality in all RCTs of adjuvant therapy for rectal cancer.

Pretreatment transcriptional profiling for predicting response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma.

PURPOSE: Patients presenting with locally advanced rectal cancer currently receive preoperative radiotherapy with or without chemotherapy. Although pathologic complete response is achieved for approximately 10% to 30% of patients, a proportion of patients derive no benefit from this therapy while being exposed to toxic side effects of treatment. Therefore, there is a strong need to identify patients who are unlikely to benefit from neoadjuvant therapy to help direct them toward alternate and ultimately more successful treatment options. EXPERIMENTAL DESIGN: In this study, we obtained expression profiles from pretreatment biopsies for 51 rectal cancer patients. All patients underwent preoperative chemoradiotherapy, followed by resection of the tumor 6 to 8 weeks posttreatment. Gene expression and response to treatment were correlated, and a supervised learning algorithm was used to generate an original predictive classifier and validate previously published classifiers. RESULTS: Novel predictive classifiers based on Mandard's tumor regression grade, metabolic response, TNM (tumor node metastasis) downstaging, and normal tissue expression profiles were generated. Because there were only 7 patients who had minimal treatment response (>80% residual tumor), expression profiles were used to predict good tumor response and outcome. These classifiers peaked at 82% sensitivity and 89% specificity; however, classifiers with the highest sensitivity had poor specificity, and vice versa. Validation of predictive classifiers from previously published reports was attempted using this cohort; however, sensitivity and specificity ranged from 21% to 70%. CONCLUSIONS: These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma.

Laparoscopic- vs. hand-assisted ultralow anterior resection: a prospective study.

PURPOSE: A standard laparoscopic-assisted operation can be conducted with colorectal anastomosis performed after extraction of specimen and insertion of a pursestring via a small left iliac fossa or suprapubic incision, or completed via hand-assisted laparoscopic technique with a 7-cm to 8-cm suprapubic incision. This study compares the short-term outcomes of either technique. METHODS: Sixty-three consecutive patients undergoing laparoscopic-assisted ultralow anterior resection or total mesorectal excision for rectal cancer were examined. The laparoscopic-assisted group (n = 31) had standard laparoscopic-assisted resection, whereas the hand-assisted laparoscopic group (n = 32) had a 7-cm to 8-cm suprapubic incision to allow an open colorectal anastomosis. In patients who were obese or have had multiple abdominal surgeries, the hand-assisted approach was generally favored. All patients had a diverting ileostomy. RESULTS: There was no conversion in either group. Mean operating time was significantly longer in the laparoscopic-assisted group (188.2 vs. 169.8 minutes; P < 0.0001). Mean duration for narcotic analgesia (1.65 vs. 3.38 days, P < 0.0001), mean time to flatus (1.97 vs. 3.19 days, P < 0.0001), and mean duration of intravenous hydration (2.45 vs. 3.88 days, P < 0.0001) were longer in the hand-assisted laparoscopic group. However, the mean length of hospital stay (5.8 vs. 5.9 days, P = 0.379) was similar. There was no major surgical complication in either group; chest infection, wound infection, and thrombophlebitis were similar between the laparoscopic-assisted group and the hand-assisted laparoscopic group. Adequacy of specimen harvest (distal tumor margins, P = 0.995; circumferential resection margin, P = 0.946; number of lymph nodes, P = 0.845) was similar. CONCLUSIONS: Although both laparoscopic-assisted and hand-assisted laparoscopic surgeries are safe and feasible for ultralow anterior resection, the hand-assisted technique significantly shortens operating time.