Position statement by the Pelvic Floor Society on behalf of the Association of Coloproctology of Great Britain and Ireland on the use of mesh in ventral mesh rectopexy.

The following position statement forms part of a response to the current concerns regarding use of mesh to perform rectal prolapse surgery. It highlights the actions being pursued by the Pelvic Floor Society (TPFS) regarding clinical governance in relation to ventral mesh rectopexy (VMR). The following are summary recommendations. Available evidence suggests that mesh morbidity for VMR is far lower than that seen in transvaginal procedures (the main subject of current concern) and lower than that observed following other abdomino-pelvic procedures for urogenital prolapse, e.g. laparoscopic sacrocolpopexy. VMR should be performed by adequately trained surgeons who work within a multidisciplinary team (MDT) framework. Within this, it is mandatory to discuss all patients considered for surgery at an MDT meeting. Clinical outcomes of surgery and any complications resulting from surgery should be recorded in the TPFS-hosted national database (registry) available for this purpose; in addition, all patients should be considered for entry into ongoing and planned UK/European randomized studies where this is feasible. A move towards accreditation of UK units performing VMR will improve performance and outcomes in the long term. An enhanced programme of training including staged porcine, cadaveric and preceptorship sessions will ensure the competence of surgeons undertaking VMR. Enhanced consent forms and patient information booklets are being developed, and these will help both surgeons and patients. There is weak observational evidence that technical aspects of the procedure can be optimized to reduce morbidity rates. Suture material choice may contribute towards morbidity. The available evidence is insufficient to support the use of one mesh over another (biologic vs synthetic); however, the use of polyester mesh is associated with increased morbidity.

Could FiLaC™ be effective in the treatment of anal fistulas? A systematic review of observational studies and proportional meta-analysis.

AIM: Fistula Laser Closure (FiLaC™) is a novel sphincter-preserving technique that is based on new technologies and shows promising results in repairing anal fistulas whilst maintaining external sphincter function. The aim of the present meta-analysis is to present the efficacy and the safety of FiLaC™ in the management of anal fistula disease. METHOD: The present proportional meta-analysis was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until November 2019. RESULTS: Overall, eight studies were included that recruited 476 patients. The pooled success rate of the technique was 63% (95% CI 50%-75%). The pooled complication rate was 8% (95% CI 1%-18%). Sixty-six per cent of patients had a transsphincteric fistula and 60% had undergone a previous surgical intervention, mainly the insertion of a seton (54%). The majority had a cryptoglandular fistula. Operation time and follow-up period were described for each study. CONCLUSION: FiLaC™ seems to be an efficient therapeutic option for perianal fistula disease with an adequate level of safety that preserves quality of life. Nevertheless, randomized trials need to be designed to compare FiLaC™ with other procedures for the management of anal fistulas such as ligation of intersphincteric fistula tract, anal advancement flaps, fibrin glue, collagen paste, autologous adipose tissue, fistula plug and video-assisted anal fistula treatment.

Intrinsic predictors of prolonged length of stay in a colorectal enhanced recovery pathway: a prospective cohort study and multivariate analysis.

AIM: This was a prospective cohort study to determine the intrinsic non-modifiable factors influencing length of stay (LOS) in unselected consecutive patients undergoing elective colorectal surgery within an enhanced recovery pathway. METHODS: This study interrogated a prospective database of consecutive elective procedures from October 2006 to April 2011 at a tertiary referral academic hospital in the UK to identify independent predictors of prolonged length of stay (pLOS). pLOS was defined as longer than median length of stay (mLOS). Differences in determinants were identified in three groups of increasing operative complexity. RESULTS: In all, 872 procedures were identified and ranged from a simple ileostomy reversal to complex total pelvic exenteration. Preoperative anaemia and American Society of Anesthesiologists (ASA) Grade III+ predicted pLOS in stoma reversal surgery patients (n = 191, mLOS 4 days). In colonic and small bowel surgery (n = 444, mLOS 8 days), an open procedure, new stoma formation, planned critical care admission and ASA III+ predicted pLOS. New stoma formation and planned critical care admission predicted pLOS in patients undergoing pelvic rectal surgery (n = 237, mLOS 11 days). pLOS was associated with significantly higher morbidity across Dindo-Clavien grades and a longer time to postoperative functional recovery and discharge. CONCLUSIONS: Operative complexity is associated with longer LOS even with an established enhanced recovery pathway in place. Intrinsic non-modifiable predictors of pLOS differ with operative complexity, and this should be taken into account when planning benchmarking and research across units.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Surgery for constipation: systematic review and practice recommendations: Results IV: Recto-vaginal reinforcement procedures.

AIM: To assess the outcomes of recto-vaginal reinforcement procedures in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Forty-three articles were identified, providing data on outcomes in 3346 patients. Average length of procedures ranged between 20 and 169 min, and length of stay between 1 and 15 days. Complications typically occurred after 7-17% of procedures (range 0-61%). Post-operative bleeding was uncommon (0-4%) as well as haematoma or sepsis (0-2%). Fistulation did not occur in most studies. Two procedure-related deaths were observed for 3209 patients. Although inconsistent, 78% of patients reported a satisfactory or good outcome, with 30-50% experiencing reduced symptoms of straining, incomplete emptying or reduced vaginal digitation. About 17% of patients developed anatomical recurrence. Considering measures of harm and global satisfaction rating scales, there was insufficient evidence to prefer one type of procedure over another. There was no evidence to support better outcomes based on selection of patients with a particular size or grade of rectocoele. CONCLUSION: Evidence supporting recto-vaginal reinforcement procedures is currently derived from observational studies and comparisons, with only one high quality study. Large trials are needed to inform future clinical decision making.

Quality of life following fistulotomy - short term follow-up.

AIM: Anal fistula causes pain and discharge of pus and blood. Treatment by fistulotomy has the highest success, but can risk continence; treatment needs to balance cure with continence. This study assessed the impact of fistulotomy on quality of life (QOL) and continence. METHOD: Patients selected for fistulotomy prospectively completed the St Mark's Continence Score (full incontinence = 24) and Short Form-36 questionnaires preoperatively at two institutions with an interest in anal fistula. Patients were reassessed 3 months' postoperatively. RESULTS: There were 52 patients with a median age of 44 (range 19-82) years; 10 were women. Preoperative continence scores were median 0 (range 0-23) and there was no significant difference compared with postoperative scores (median 1, range 0-24). Following fistulotomy QOL was significantly improved in four of eight domains - Bodily Pain (P < 0.001), Vitality (P < 0.01), Social Functioning (P < 0.05) and Mental Health (P < 0.001) - and returned to that of the general population. QOL for patients with intersphincteric fistula improved postfistulotomy, and for those with trans-sphincteric fistula it remained the same. Data were further examined in two groups, with and without deterioration in continence score. Where continence improved postoperatively, QOL improved in three domains; where continence deteriorated QOL improved in two domains (P < 0.05). Patients with postoperative continence scores of < 5 had worse QOL than those scoring 4 or less. CONCLUSION: QOL significantly improved at 3 months' follow-up after fistulotomy where continence was maintained or a small reduction occurred.

Integrated total pelvic floor ultrasound in pelvic floor defaecatory dysfunction.

AIM: Imaging for pelvic floor defaecatory dysfunction includes defaecation proctography. Integrated total pelvic floor ultrasound (transvaginal, transperineal, endoanal) may be an alternative. This study assesses ultrasound accuracy for the detection of rectocele, intussusception, enterocele and dyssynergy compared with defaecation proctography, and determines if ultrasound can predict symptoms and findings on proctography. Treatment is examined. METHOD: Images of 323 women who underwent integrated total pelvic floor ultrasound and defaecation proctography between 2011 and 2014 were blindly reviewed. The size and grade of rectocele, enterocele, intussusception and dyssynergy were noted on both, using proctography as the gold standard. Barium trapping in a rectocele or a functionally significant enterocele was noted on proctography. Demographics and Obstructive Defaecation Symptom scores were collated. RESULTS: The positive predictive value of ultrasound was 73% for rectocele, 79% for intussusception and 91% for enterocele. The negative predictive value for dyssynergy was 99%. Agreement was moderate for rectocele and intussusception, good for enterocele and fair for dyssynergy. The majority of rectoceles that required surgery (59/61) and caused barium trapping (85/89) were detected on ultrasound. A rectocele seen on both transvaginal and transperineal scanning was more likely to require surgery than if seen with only one mode (P = 0.0001). If there was intussusception on ultrasound the patient was more likely to have surgery (P = 0.03). An enterocele visualized on ultrasound was likely to be functionally significant on proctography (P = 0.02). There was, however, no association between findings on imaging and symptoms. CONCLUSION: Integrated total pelvic floor ultrasound provides a useful screening tool for women with defaecatory dysfunction such that defaecatory imaging can avoided in some.

Surgery for constipation: systematic review and practice recommendations: Graded practice and future research recommendations.

AIM: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). METHODS: Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. RESULTS: The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. CONCLUSION: While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.

Surgery for constipation: systematic review and clinical guidance: Paper 1: Introduction & Methods.

AIM: This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. METHOD: PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion; (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. RESULTS: An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40); (ii) rectal suspension (n = 18); (iii) rectal wall excision (n = 44); (iv) rectovaginal septum reinforcement (n = 47); (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. CONCLUSION: This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.

The future of pelvic floor services in the UK.

AIM: The study aimed to determine the current state of UK pelvic floor services and to discuss future strategies. METHOD: A questionnaire developed by the Pelvic Floor Society was sent in 2014 to the 175 colorectal units recognized by the Association of Coloproctology of Great Britain and Ireland. Questions included type of centre, frequency of pelvic floor clinics/interdisciplinary joint pelvic floor clinics/multidisciplinary meetings (MDMs) and workload. RESULTS: Sixty-seven (38%) centres replied including 75% of units with a consultant who was as member of the Pelvic Floor Society. Of the 67 centres 39% were tertiary centres for pelvic floor surgery (tertiary), 48% performed some pelvic floor surgery (regional) and 13% did not perform any (local). Ninety-six per cent of tertiary referral centres served a population over 500 000. The mean number of whole time equivalent consultants in tertiary centres was 1.03 and 0.77 in regional centres. Eighty per cent of tertiary centres and 56% of regional centres ran pelvic floor clinics. Eighty-four per cent of tertiary referral and 75% of regional units held or attended an MDM. Anal ultrasonography, anorectal physiology and proctography were performed in 96% of tertiary centres compared with 50% of non-tertiary units. CONCLUSION: The provision of pelvic floor services includes local, regional and tertiary centres. The overall response rate was low (38%) and biased to centres with a consultant who was a member of the Pelvic Floor Society. Not all regional or tertiary centres held an MDM or a pelvic floor clinic. Given the nature of pelvic floor pathology an integrated service should be aimed at linking different centres and specialities.

Short- and long-term outcome of laparostomy following intra-abdominal sepsis.

AIM: This study reports the short- and long-term outcomes of laparostomy for intra-abdominal sepsis. METHOD: Twenty-nine sequential patients with intra-abdominal sepsis treated with a laparostomy over 6 years were included. RESULTS: The median age of the patients was 51 years, postoperative intensive care unit stay was 8 days, postoperative length of hospital stay was 87 days and follow up was 2 years. The expected mortality of 25% was insignificantly different from the observed mortality of 33% (P = 0.35). Seven per cent of patients required percutaneous drainage of intra-abdominal collections. An enterocutaneous fistula developed in 31% of all patients and in 15% of those treated with vacuum dressings. Component-separation fascial reconstruction was successful and uncomplicated in 83% of recipients compared with 25% of mesh repairs. CONCLUSION: Laparostomy does not significantly reduce mortality from the expected rate and commits the patient to a prolonged recovery with a high risk of enterocutaneous fistulation. Component-separation fascial reconstruction has a better outcome than mesh repair.

Use of myocutaneous flaps for perineal closure following abdominoperineal excision of the rectum for adenocarcinoma.

INTRODUCTION: Abdominoperineal excision (APE) following radiotherapy is associated with a high rate of perineal wound complications. The use of myocutaneous flaps may improve wound healing. We present our experience using myocutaneous flaps for immediate reconstruction. METHOD: Prospective data were collected on patients undergoing APE from October 2003 to December 2008. Patient demographics, operating time, wound complications and length of stay were recorded. RESULTS: Fifty-one patients underwent APE for rectal adenocarcinoma, 21 had primary closure and 30 had myocutaneous flap closure (24 VRAM, 6 gracilis). The proportion of patients undergoing preoperative radiotherapy in each group were 62% and 93% respectively (P = 0.011). There were no major complications following primary closure of the unirradiated perineum. Major perineal wound complications requiring reoperation or debridement were seen in three (14%) patients following primary closure and five (17%) patients with flap closure. After radiotherapy, closure with a flap reduced the length of stay from 20 to 15 days, but this difference was not statistically significant (P = 0.36). CONCLUSION: The use of flap closure in irradiated patients is associated with fewer perineal complications and a shorter hospital stay.

Outcome of patients on renal replacement therapy after colorectal surgery.

PURPOSE: Patients on renal replacement therapy are reported to have a high complication rate after abdominal surgery, the result of uremia and immunosuppression. A review of this group of patients undergoing colorectal surgery was undertaken. METHODS: Seventy-three separate colorectal operations were performed for 44 patients. Thirty-eight patients were on dialysis and 35 had a renal transplant. Data (coexisting disease, preoperative blood results, operative details, complications, and colorectal POSSUM score) were completed for each surgical event. RESULTS: Forty-two elective and 31 emergency procedures were performed. Infective complications were common (overall 60 percent). There were two anastomotic leaks in the elective group, but five leaks from seven emergency anastomoses. Stomas were frequently raised. Ninety percent of patients who survived and had a defunctioning stoma underwent a successful reversal. The overall major complication rate after elective and emergency surgery was 19 and 81 percent, respectively, and mortality was 5 and 26 percent, respectively. CONCLUSIONS: Renal patients have a high rate of complications after colorectal surgery, and emergency surgery has a significant risk of anastomotic leak. Primary anastomosis should be avoided in all patients undergoing emergency intestinal resections. Subsequent surgery to restore intestinal continuity is possible in 90 percent of patients with far fewer complications.

Effect of commercial airline travel on oxygen saturation in athletes.

BACKGROUND: Aircraft cabins are pressurised to maximum effective altitudes of 2440 metres, resulting in significant decline in oxygen saturation in crew and passengers. This effect has not been studied in athletes. OBJECTIVE: To investigate the degree of decline in oxygen saturation in athletes during long-haul flights. METHODS: A prospective cross-sectional study. National-level athletes were recruited. Oxygen saturation and heart rate were measured with a pulse oximeter at sea level before departure, at 3 and 7 hours into the flight, and again after arrival at sea level. Aircraft cabin pressure and altitude, cabin fraction of inspired oxygen and true altitude were also recorded. RESULTS: 45 athletes and 18 healthy staff aged between 17 and 70 years were studied on 10 long-haul flights. Oxygen saturation levels declined significantly after 3 hours and 7 hours (3-4%), compared with sea level values. There was an associated drop in cabin pressure and fraction of inspired oxygen, and an increase in cabin altitude. CONCLUSIONS: Oxygen saturation declines significantly in athletes during long-haul commercial flights, in response to reduced cabin pressure. This may be relevant for altitude acclimatization planning by athletes, as the time spent on the plane should be considered time already spent at altitude, with associated physiological changes. For flights of 10-13 hours in duration, it will be difficult to arrive on the day of competition to avoid the influence of these changes, as is often suggested by coaches.

Synchronized functional anal sphincter assessment: maximizing the potential of anal vector manometry and 3-D anal endosonography.

BACKGROUND: Understanding the association between structure and function is vital before considering surgery involving anal sphincter division. By correlating three-dimensional anal endosonography (AES) and three-dimensional anal canal vector volume manometry (VVM), this study details a method to produce measurements of both sphincter length and pressure leading to identification of the functionally important areas of the anal canal. The aim of this study was to provide combined detailed information on anal canal anatomy and physiology. METHODS: Twelve males and 12 nulliparous females with no bowel symptoms underwent VVM (using a water-perfused, eight-channel radially arranged catheter) and AES. KEY RESULTS: The synchronization of AES and VVM identified that the majority of rest and squeeze anal pressure is present in the portion of the anal canal covered by both anal sphincters. Nearly, 20% of overall resting anal pressure is produced distal to the caudal termination of the internal anal sphincter. Puborectalis accounts for a significantly greater percentage volume of pressure in females both at rest and when squeezing, though the total volume of pressure is not significantly greater. CONCLUSIONS AND INFERENCES: The majority of resting and squeezing pressure and the least asymmetry, in both sexes, is in the portion of the anal canal covered by external anal sphincter. In females, the external anal sphincter is shorter and a proportionately longer puborectalis accounts for a greater percentage of pressure. Sphincter targeted fistula surgery in females must be performed with special caution. A protective role for puborectalis following obstetric anal sphincter injury is suggested.

Quality of life with anal fistula.

INTRODUCTION: Anal fistula affects people of working age. Symptoms include abscess, pain, discharge of pus and blood. Treatment of this benign disease can affect faecal continence, which may, in turn, impair quality of life (QOL). We assessed the QOL of patients with cryptoglandular anal fistula. METHODS: Newly referred patients with anal fistula completed the St Mark's Incontinence Score, which ranges from 0 (perfect continence) to 24 (totally incontinent), and Short form 36 (SF-36) questionnaire at two institutions with an interest in anal fistula. The data were examined to identify factors affecting QOL. RESULTS: Data were available for 146 patients (47 women), with a median age of 44 years (range 18-82 years) and a median continence score of 0 (range 0-23). Versus population norms, patients had an overall reduction in QOL. While those with recurrent disease had no difference on continence scores, QOL was worse on two of eight SF-36 domains (p<0.05). Patients with secondary extensions had reduced QOL in two domains (p<0.05), while urgency was associated with reduced QOL on five domains (p<0.05). Patients with loose seton had the same QOL as those without seton. No difference in urgency was found between patients with and without loose seton. In primary fistula patients, 19.4% of patients experienced urgency versus 36.3% of those with recurrent fistulas. CONCLUSIONS: Patients with anal fistula had a reduced QOL, which was worse in those with recurrent disease, secondary extensions and urgency. Loose seton had no impact on QOL.

Rewarming of healthy volunteers after induced mild hypothermia: a healthy volunteer study.

OBJECTIVES: The study compares the efficacy of two active and one passive warming interventions in healthy volunteers with induced mild hypothermia. METHODS: Eight volunteers were studied in a random order crossover design. Each volunteer was studied during re-warming from a core temperature of 35 degrees C with each of: a radiant warmer (Fisher & Paykel); a forced air warmer (Augustine Medical), and a polyester filled blanket, to re-warm. RESULTS: No significant differences in re-warming rates were observed between the three warming devices. It was found that the subject's endogenous heat production was the major contributor to the re-warming of these volunteers. Metabolic rates of over 350 W were seen during the study. CONCLUSIONS: For patients with mild hypothermia and in whom shivering is not contraindicated our data would indicate that the rate of re-warming would be little different whether a blanket or one of the two active devices were used. In the field, this may provide the caregiver a useful choice.

Race/ethnicity as a risk factor for HIV-1 infection among Connecticut intravenous drug users.

This cross-sectional study of 341 entrants to drug abuse treatment in four Connecticut cities in 1986-1987 evaluated whether demographic, behavioral, viral serologic, or economic differences explained the disproportionate risk of human immunodeficiency virus type 1 (HIV-1) infection among black and Hispanic intravenous drug users (IVDUs), relative to non-Hispanic white IVDUs. Blacks [odds ratio (OR) = 9.0, 95% confidence interval (CI) = 5.1-15.9] and Hispanics (OR = 4.1, 95% CI = 1.9-8.8) were at increased risk of HIV-1 infection, relative to non-Hispanic whites. Those who lived closer to New York City, injected drugs more frequently, used intravenous drugs for a longer duration, used shooting galleries, had greater numbers of sexual partners, had human cytomegalovirus (CMV) or hepatitis B virus (HBV) antibodies, and had the lowest annual incomes were also at increased risk. However, none of these other factors accounted for the black and Hispanic HIV-1 risk in stratified analysis. Black race, Hispanic ethnicity, proximity to New York City, and number of drug injections in the past year each also remained significant, independent risk factors in a multivariate analysis. The increased HIV-1 risk of nonwhite IVDUs remained unexplained. Behavioral, sociologic, and/or biologic factors not identified in this study may modulate HIV-1 transmission dynamics in IVDUs.

A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line.

A cyclic octapeptide (patellamide D) isolated from the marine tunicate, Lissaclinum patella, acts as a resistance-modifying agent in the multidrug resistant CEM/VLB100 human leukemic cell line. A three-day microculture tetrazolium proliferation assay was used to determine the 50% inhibitory concentration (IC50) for vinblastine, colchicine and adriamycin and calculate the degree of resistance modulation. Patellamide D at 3.3 microM was compared with 5.1 microM verapamil in modulating drug resistance in vitro. The IC50 for vinblastine was reduced from 100 ng/ml to 1.5 ng/ml in the presence of patellamide D or to 2.1 ng/ml when exposed to verapamil. Colchicine cytotoxicity was enhanced only 1.4-fold by verapamil, as compared with 2.8-fold using patellamide D (IC50 was reduced from 140 ng/ml to 100 ng/ml or 50 ng/ml). Adriamycin toxicity was reduced from IC50 > 1000 ng/ml to 110 ng/ml and 160 ng/ml when coexposed to patellamide D and verapamil, respectively. Our results indicate that patellamide D acts as a selective antagonist in multidrug resistance and stresses the importance of investigating marine-derived compounds as a potential new source for modulators of the drug-resistance phenotype.

Response of fistulating Crohn's disease to infliximab treatment assessed by magnetic resonance imaging.

AIMS: To assess fistula track healing after infliximab treatment using magnetic resonance imaging. METHODS: Magnetic resonance imaging and clinical evaluation were performed before and after three infliximab infusions given over a 6-week period. Magnetic resonance images were evaluated for abscesses and fistula tracks. Paired magnetic resonance image examinations were rated 'better', 'unchanged' or 'worse'. Magnetic resonance imaging and clinical outcomes were then compared. RESULTS: Of the 12 referred patients, pre-treatment magnetic resonance imaging detected abscesses in three (two not treated). Of the 10 treated patients, seven had peri-anal fistulas, two of whom also had recto-vaginal fistulas, and three had abdominal wall entero-cutaneous fistulas. After infliximab, four were in remission, one had a response and five were non-responders. One developed a peri-anal abscess. Magnetic resonance imaging improved in six, was unchanged in two and was worse in two. In four of the six with improvement in magnetic resonance imaging, the fistula track resolved, but two of these had clinically persistent entero-cutaneous fistulas. The clinical outcome and magnetic resonance imaging correlated in seven of the 10 patients; in three (two entero-cutaneous and one peri-anal), there was discordance. CONCLUSIONS: Magnetic resonance imaging identifies clinically silent sepsis. Fistulas may persist despite clinical remission. Clinical response to infliximab and clinical correlation with magnetic resonance imaging were poor in patients with abdominal entero-cutaneous fistulas.