Use of the eLogbook in surgical training in the United Kingdom: A nationwide survey and consensus recommendations from the Association of Surgeons in Training.

INTRODUCTION: Accurate recording of operative cases is essential during training to demonstrate experience. However, indicative numbers delineating minimum desirable experience may incentivise exaggeration or misrepresentation of experience. This study aimed to determine perceptions of real-world eLogbook use among UK surgeons in training. MATERIAL AND METHODS: An anonymous online questionnaire was disseminated electronically using a pre-planned yield-maximisation strategy, incorporating regional champions, email and social media. Evaluation employed mixed methods in a combined interpretation of quantitative and qualitative data from the questionnaire. Recommendations for development of the eLogbook were itemised from respondents' free text items and a modified Delphi process, conducted within the Council of the UK national trainee representative body, the Association of Surgeons in Training, determined the strength of each recommendation. RESULTS: Analysis included 906 complete responses from training-grade surgeons (34.8% female) from all UK recognised specialties and all grades of training. More than two-thirds (68.5%) believed that overstatement or misrepresentation of case involvement occurs. A fifth (20.8%) reported witnessing trainees logging cases they had not actually participated in and almost a third (32.7%) had witnessed overstatement, yet few (15.1%) had raised such an issue with a supervisor. Most (85.2%) respondents had few or no eLogbook entries validated. More than a quarter of respondents felt pressure to overstate their involvement in cases (28.6%) and the number recorded (28.1%). Almost a third (31.5%) felt the required case number for completion of training was not achievable. Female trainees were less likely to feel well supervised (p = 0.022) and to perceive targets for completion of training were achievable (p = 0.005). Thematic analysis identified four key themes to explain logbook misuse: Pressure to achieve training milestones; eLogbook functionality issues; training deficiencies and probity. CONCLUSIONS: Inaccurate operative recording was widely reported, primarily in response to perceived pressure to achieve targets for career progression. Operative logbooks may not be as accurate as intended. Consensus recommendations are made for improvement in the eLogbook and its use.

The effect of training order on neuromuscular, endocrine and mood response to small-sided games and resistance training sessions over a 24-h period.

OBJECTIVES: This study examined the acute effect of small-sided-game (SSG) and resistance training sequence on neuromuscular, endocrine and mood response over a 24-h (h) period. DESIGN: Repeated measures. METHODS: Fourteen semi-professional soccer players performed SSG-training (4vs4+goalkeepers; 6×7-min, 2-min inter-set recovery) followed by resistance training 2h later (back-squat, Romanian deadlift, barbell-hip-thrust; 4×4 repetitions, 4-min inter-set recovery; 85% 1 rep-max) (SSG+RES), and on a separate week reversed the session order (RES+SSG). Physical demands of SSG's were monitored using global positioning systems (GPS) and ratings of perceived exertion (RPE). Countermovement-jump (CMJ; peak power output; jump height) and brief assessment of mood were collected before (pre), during (0h) and after (+24h) both protocols. Salivary testosterone and cortisol concentrations were obtained at the same time-points but with the inclusion of a measure immediately prior to the second training session (+2h). RESULTS: GPS outputs and RPE were similar between SSG-training during both protocols. Between-protocol comparisons revealed no significant differences at +24h in CMJ performance, mood, and endocrine markers. Testosterone was higher at 0h during RES+SSG in comparison to SSG+RES (moderate-effect; +21.4±26.7pgml-1; p=0.010), yet was similar between protocols by +2h. CONCLUSIONS: The order of SSG and resistance training does not appear to influence the physical demands of SSG's with sufficient recovery between two sessions performed on the same day. Session order did not influence neuromuscular, endocrine or mood responses at +24h, however a favourable testosterone response from the resistance first session may enhance neuromuscular performance in the second session of the day.

The neuromuscular, endocrine and mood responses to a single versus double training session day in soccer players.

OBJECTIVES: This study profiled the 24h neuromuscular, endocrine and mood responses to a single versus a double training day in soccer players. DESIGN: Repeated measures. METHODS: Twelve semi-professional soccer players performed small-sided-games (SSG's; 4 vs 4+goalkeepers; 6×7-min, 2-min inter-set recovery) with neuromuscular (peak-power output, PPO; jump height, JH), endocrine (salivary testosterone, cortisol), and mood measures collected before (pre) and after (0h, +24h). The following week, the same SSG protocol was performed with an additional lower body strength training session (back-squat, Romanian deadlift, barbell hip thrust; 4×4 repetitions, 4-min inter-set recovery; 85% 1 rep-max) added at 2h after the SSG's. RESULTS: Between-trial comparisons revealed possible to likely small impairments in PPO (2.5±2.2Wkg-1; 90% Confidence Limits: ±2.2Wkg-1), JH (-1.3; ±2.0cm) and mood (4.6; ±6.1AU) in response to the double versus single sessions at +24h. Likely to very likely small favourable responses occurred following the single session for testosterone (-15.2; ±6.1pgml-1), cortisol (0.072; ±0.034ugdl-1) and testosterone/cortisol ratio (-96.6; ±36.7AU) at +24h compared to the double session trial. CONCLUSIONS: These data highlight that performance of two training sessions within a day resulted in possible to very likely small impairments of neuromuscular performance, mood score and endocrine markers at +24h relative to a single training session day. A strategy of alternating high intensity explosive training days containing multiple sessions with days emphasising submaximal technical/tactical activities may be beneficial for those responsible for the design and delivery of soccer training programs.

The differential effect of sub-micron level HA aggregates on influenza potency assays.

Influenza vaccines remain the most effective public health measure for the prevention of influenza-related illnesses. The primary immunogen in inactivated influenza vaccines is hemagglutinin (HA), the receptor binding protein of influenza. The concentration of HA during vaccine production and testing is standardized according to the level of antigen as measured by Single Radial Immunodiffusion Assay (SRID). This allows vaccine potency to be controlled such that individuals receive a dose known to provoke a clinically protective immune response. As compared to alternatives, SRID has the advantage of quantifying immunologically relevant forms of HA, but it depends on timely generation of novel reagents for each new vaccine strain. In recent years, a number of alternative assays have been suggested based on either epitope recognition, receptor binding or protection from proteolysis but it is unclear how they relate to vaccine potency in clinical trials. In this report we describe the development of a lectin-based, ELISA-type assay for HA potency and find it provides similar potency estimates to SRID except in the case of a vaccine with aggregated HA and other viral proteins. In that case, SRID predicted the immunologically active HA present and ELISA techniques did not. This difference was due to tested antibodies failing to pull down or bind to the HA present unless particle aggregates were first dissociated. Furthermore, detergent treatment alone was insufficient to complete this dissociation. While others have previously demonstrated that immunocapture-based techniques can misestimate the potency of influenza vaccines depending on the individual antibodies used we demonstrate that in this case the failure was due to an inability of all antibodies to capture HA contained in the aggregated influenza vaccine.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Systematic review with meta-analysis of the impact of surgical fellowship training on patient outcomes.

BACKGROUND: The number of surgeons entering fellowship training before independent practice is increasing. This may have a negative impact on surgeons in training. The impact of fellowship training on patient outcomes is not yet known. This review aimed to investigate the impact of fellowship training in surgery on patient outcomes. METHODS: A systematic review of the literature was conducted to identify studies exploring the structural and surgeon-specific characteristics of fellowship training on patient outcomes. Data from these studies were extracted, synthesized and reported qualitatively, or quantitatively through meta-analysis. RESULTS: Twenty-three studies were included. The mortality rate for patients in centres with an affiliated fellowship programme was lower than that for centres without (odds ratio 0.86, 95 per cent c.i. 0.84 to 0.88), as was the rate of complications (odds ratio 0.90, 0.78 to 1.02). Surgeons without fellowship training converted more laparoscopic operations to open surgery than those with fellowship training (risk ratio (RR) 1.04, 95 per cent c.i. 1.03 to 1.05). Comparison of outcomes for senior surgeons versus current fellows showed no differences in rates of mortality (RR 1.00, 1.00 to 1.01), complications (RR 1.03, 0.98 to 1.08) or conversion to open surgery (RR 1.01, 1.00 to 1.01). CONCLUSION: Fellowship training appears to have a positive impact on patient outcomes.

A randomised controlled trial of fluid restriction compared to oesophageal Doppler-guided goal-directed fluid therapy in elective major colorectal surgery within an Enhanced Recovery After Surgery program.

There is continued controversy regarding the benefits of goal-directed fluid therapy, with earlier studies showing marked improvement in morbidity and length-of-stay that have not been replicated more recently. The aim of this study was to compare patient outcomes in elective colorectal surgery patients having goal-directed versus restrictive fluid therapy. Inclusion criteria included suitability for an Enhanced Recovery After Surgery care pathway and patients with an American Society of Anesthesiologists Physical Status score of 1 to 3. Patients were intraoperatively randomised to either restrictive or Doppler-guided goal-directed fluid therapy. The primary outcome was length-of-stay; secondary outcomes included complication rate, change in haemodynamic variables and fluid volumes. Compared to restrictive therapy, goal-directed therapy resulted in a greater volume of intraoperative fluid, 2115 (interquartile range 1350 to 2560) ml versus 1500 (1200 to 2000) ml, P=0.008, and was associated with an increase in Doppler-derived stroke volume index from beginning to end of surgery, 43.7 (16.3) to 54.2 (21.1) ml/m(2), P <0.001, in the latter group. Length-of-stay was similar, 6.5 (5 to 9) versus 6 (4 to 9) days, P=0.421. The number of patients with any complication (minor or major) was similar; 0% (30) versus 52% (26), P=0.42, or major complications, 1 (2%) versus 4 (8%), P=0.36, respectively. The increased perioperative fluid volumes and increased stroke volumes at the end of surgery in patients receiving goal-directed therapy did not translate to a significant difference in length-of-stay and we did not observe a difference in the number of patients experiencing minor or major complications.

Outpatient management of biliary colic: a prospective observational study of prescribing habits and analgesia effectiveness.

BACKGROUND: Uncomplicated biliary colic presents a significant health and financial burden to hospitals and primary care services alike. There is little guidance on the correct analgesia to use on an outpatient basis. This study aimed to evaluate the effectiveness of oral analgesics on biliary colic pain and to explore the prescribing habits of community doctors. METHODS: Consecutive patients with ultrasound proven symptomatic gallstones completed a questionnaire recording demographics and symptomatology. Pain was assessed using a visual analogue scale (VAS) based on the Biliary Symptom Score (BSS) to evaluate the effectiveness of various analgesic agents. Local General Practitioners were also surveyed to establish prescribing practices. RESULTS: Co-Codamol had the highest mean effectiveness VAS score (6.5/10). Patients with increased BMI, short symptom duration and a BSS >70 were most likely to suffer from severe pain. Patients in a subgroup with severe pain were most likely to have their pain reduced by NSAID analgesia compared to no NSAID (OR 2.20, p = 0.027). This effect remained significant upon multivariable regression (OR 2.52, p = 0.018) in a model containing age and NSAIDs. There was wide variation in the prescribing practice of GPs and hospital doctors. CONCLUSIONS: The range of drugs prescribed for biliary colic is extensive with little evidence base. In this study NSAIDs were the most effective analgesia for patients with severe pain. In the absence of contraindications to their use, physician education or guidance emphasizing the benefits of NSAIDs may potentially reduce symptomatic hospital presentation and admissions for biliary colic.

Postoperative recurrence of Crohn's disease: impact of endoscopic monitoring and treatment step-up.

AIM: Eighty per cent of patients with Crohn's disease require surgery, of whom 70% will require a further operation. Recurrence occurs at the anastomosis. Although often recommended, the impact of postoperative colonoscopy and treatment adjustment is unknown. METHOD: Patients with a bowel resection over a 10-year period were reviewed and comparison made between those who did and did not have a postoperative colonoscopy within 1 year of surgery, and those who did or did not have a step-up in drug therapy. RESULTS: Of 222 patients operated on, 136 (65 men, mean age 33 years, mean disease duration 8 years, median follow-up 4 years) were studied. Of 70 patients with and 66 without postoperative colonoscopy, clinical recurrence occurred in 49% and 48% (NS) and further surgery in 9% and 5% (NS). Eighty-nine per cent of colonoscoped patients had a decision based on the colonoscopic findings: of these, 24% had a step-up of drug therapy [antibiotics (n =10), aminosalicylates (n=2), thiopurine (n=5), methotrexate (n=1)] and 76% had no step-up in drug therapy. In colonoscoped patients clinical recurrence occurred in 9 (60%) of 15 patients with, and 23 (49%) of 47 without step-up and surgical recurrence in 2 (13%) of 15 and 4 (9%) of 47 (NS). CONCLUSION: Clinical recurrence occurs in a majority of patients soon after surgery. In this cohort, there was no clinical benefit from colonoscopy or increased drug therapy within 1 year after operation. However, the response to the endoscopic findings was not standardized and immunosuppressive therapy was uncommon. Standardizing timing of colonoscopy and drug therapy, including more intense therapy, may improve outcome, although this remains to be proven.

An unusual case of pancreatic fistula.

We report an unusual case of a pancreatic fistula communicating with an appendicectomy wound. This occurred following an episode of acute haemorrhagic pancreatitis. The patient was initially admitted with signs and symptoms indicating appendicitis and went to theatre for an open appendicectomy. However, this did not resolve his symptoms and a laparotomy was performed the next day revealing haemorrhagic pancreatitis. He endured a stormy post-operative course, the cause of which was found to be an external pancreatic fistula with discharge of amylase-rich fluid from the Lanz incision. A trial of conservative management failed despite multiple percutaneous drainage procedures and treatment with broad-spectrum antibiotics. After a second opinion was sought, it was decided to fit a roux loop anastomosis between the head of the pancreas and the duodenum to divert the fistulous fluid. This procedure was a success and the patient remains well 2 years later.

Distinct levels of Sox9 expression mark colon epithelial stem cells that form colonoids in culture.

Sox9 is an high-mobility group box transcription factor that is expressed in the stem cell zone of the small intestine and colon. We have previously used a Sox9EGFP mouse model to demonstrate that discrete levels of Sox9 expression mark small intestine epithelial stem cells that form crypt/villus-like structures in a three-dimensional culture system (Formeister EJ, Sionas AL, Lorance DK, Barkley CL, Lee GH, Magness ST. Am J Physiol Gastrointest Liver Physiol 296: G1108-G1118, 2009; Gracz AD, Ramalingam S, Magness ST. Am J Physiol Gastrointest Liver Physiol 298: G590-G600, 2010). In the present study, we hypothesized that discrete levels of Sox9 expression would also mark colonic epithelial stem cells (CESCs). Using the Sox9EGFP mouse model, we show that lower levels of Sox9 mark cells in the transit-amplifying progenitor cell zone, while higher levels of Sox9 mark cells in the colonic crypt base. Furthermore, we demonstrate that variable SOX9 levels persist in cells of colonic adenomas from mice and humans. Cells expressing lower Sox9 levels demonstrate gene expression profiles consistent with more differentiated populations, and cells expressing higher Sox9 levels are consistent with less differentiated populations. When placed in culture, cells expressing the highest levels of Sox9 formed "colonoids," which are defined as bodies of cultured colonic epithelial cells that possess multiple cryptlike structures and a pseudolumen. Cells expressing the highest levels of Sox9 also demonstrate multipotency and self-renewal in vitro, indicating functional stemness. These data suggest a dose-dependent role for Sox9 in normal CESCs and cells comprising colon tumors. Furthermore, distinct Sox9 levels represent a new biomarker to study CESC and progenitor biology in physiological and disease states.

Faecal diversion in the management of perianal Crohn's disease.

AIM: Severe perianal Crohn's disease remains an uncommon but important indication for faecal diversion (FD). The advent of biological therapy such as infliximab for Crohn's disease is considered to have improved the outcome for these patients. The aim of this study was to assess the outcome of patients undergoing FD for perianal Crohn's disease and the impact of biological therapy (infliximab). METHOD: Retrospective chart review was undertaken of patients who underwent FD for management of perianal Crohn's disease at two tertiary centres between 1990 and 2007. Patient demographics, disease extent and use of biological therapy were recorded. Subsequent surgery was assessed. The impact of infliximab on rates of proctocolectomy and restoration of intestinal continuity was assessed. RESULTS: Twenty-one patients (one male, 20 female), median age 34 years (range 21-67 years), underwent FD for perianal Crohn's disease. At a median follow-up time of 22 months (range 4-121 months), four patients had undergone stoma closure, 11 had had proctocolectomy and six had a stoma in situ. The effects of the procedure on severity of perianal disease were no effect in four (19%), temporary improvement in six (29%), initial improvement with later plateau in seven (33%) and healing in four patients (19%). Eleven patients (52%) received infliximab. In this group, four underwent proctocolectomy and two had intestinal continuity restored. This was not significantly different from the noninfliximab group. CONCLUSION: Patients undergoing FD for perianal Crohn's disease have <20% likelihood of restoration of intestinal continuity. This is not improved with biological therapy.

FMRFamide-like peptides in root knot nematodes and their potential role in nematode physiology.

FMRFamide-like peptides (FLPs) are a diverse group of neuropeptides that are expressed abundantly in nematodes. They exert potent physiological effects on locomotory, feeding and reproductive musculature and also act as neuromodulators. However, little is known about the specific expression patterns and functions of individual peptides. The current study employed rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR) to characterize flp genes from infective juveniles of the root knot nematodes, Meloidogyne incognita and Meloidogyne minor. The peptides identified from these transcripts are sequelogs of FLPs from the free-living nematode, Caenorhabditis elegans; the genes have therefore been designated as Mi-flp-1, Mi-flp-7, Mi-flp-12, Mm-flp-12 and Mi-flp-14. Mi-flp-1 encodes five FLPs with the common C-terminal moiety, NFLRFamide. Mi-flp-7 encodes two copies of APLDRSALVRFamide and APLDRAAMVRFamide and one copy of APFDRSSMVRFamide. Mi-flp-12 and Mm-flp-12 encode the novel peptide KNNKFEFIRFamide (a longer version of RNKFEFIRFamide found in C. elegans). Mi-flp-14 encodes a single copy of KHEYLRFamide (commonly known as AF2 and regarded as the most abundant nematode FLP), and a single copy of the novel peptide KHEFVRFamide. These FLPs share a high degree of conservation between Meloidogyne species and nematodes from other clades, including those of humans and animals, perhaps suggesting a common neurophysiological role which may be exploited by novel drugs. FLP immunoreactivity was observed for the first time in Meloidogyne, in the circumpharyngeal nerve ring, pharyngeal nerves and ventral nerve cord. Additionally, in situ hybridization revealed Mi-flp-12 expression in an RIR-like neuron and Mi-flp-14 expression in SMB-like neurons, respectively. These localizations imply physiological roles for FLP-12 and FLP-14 peptides, including locomotion and sensory perception.

Extracts of the rat tapeworm, Hymenolepis diminuta, suppress macrophage activation in vitro and alleviate chemically induced colitis in mice.

Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) and poly(I:C)-induced TNF-alpha and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and alpha-mannosidase failed to inhibit its blockade of LPS-induced TNF-alpha production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-alpha production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.

Parasitic helminths: a pharmacopeia of anti-inflammatory molecules.

SUMMARY: Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Implications for prediction and hazard assessment from the 2004 Parkfield earthquake.

Obtaining high-quality measurements close to a large earthquake is not easy: one has to be in the right place at the right time with the right instruments. Such a convergence happened, for the first time, when the 28 September 2004 Parkfield, California, earthquake occurred on the San Andreas fault in the middle of a dense network of instruments designed to record it. The resulting data reveal aspects of the earthquake process never before seen. Here we show what these data, when combined with data from earlier Parkfield earthquakes, tell us about earthquake physics and earthquake prediction. The 2004 Parkfield earthquake, with its lack of obvious precursors, demonstrates that reliable short-term earthquake prediction still is not achievable. To reduce the societal impact of earthquakes now, we should focus on developing the next generation of models that can provide better predictions of the strength and location of damaging ground shaking.

Infliximab in the surgical management of complex fistulating anal Crohn's disease.

OBJECTIVES: To assess prospectively the efficacy and safety of treatment of perianal Crohn's disease by means of a combination of surgical management and a standardized protocol for the intravenous infusion of infliximab. METHODS: A consecutive series of patients who presented with complex perianal Crohn's fistulae between November 1999 and March 2003 were included in the study. Perianal sepsis was eradicated with drainage of collections and insertion of setons. Infliximab was infused at 5 mg/kg at 0, 2, and 6 weeks. Setons were removed after the second infliximab infusion. Endpoints were defined as either complete, partial or no response as noted at subsequent outpatient follow up. Adverse reactions were recorded. RESULTS: Twenty-one patients had a median of three fistulae per patient (range 1-9). All patients tolerated the initial protocol, receiving a median of five infusions of infliximab (range 3-19); median follow up 20 months (range 12-52). Eleven patients (53%) were continued on maintenance therapy with 12 weekly infusions of infliximab for either a perceived clinical need for treatment or after a relapse of their symptoms. Ten (47%) patients experienced a complete response to treatment and the remaining 11 (53%) experienced a partial response. No patient failed to respond to treatment. Four adverse reactions were noted (2 mild allergies, 1 rash and 1 patient experienced joint pains). All adverse reactions settled with cessation of the drug infusion. CONCLUSIONS: The combination of seton drainage and infusion of infliximab completely healed the perineum of 47% patients with complex fistulating perianal Crohn's disease. Partial response was seen in the remainder of patients. No serious adverse reactions reported.

Reasons for failure to diagnose colorectal carcinoma at colonoscopy.

BACKGROUND AND STUDY AIMS: Colonoscopy can produce false-negative results, and the reasons for this remain obscure. The aim of this study was to examine why cancers are missed at colonoscopy. PATIENTS AND METHODS: All colonoscopies carried out at Christchurch Hospital, New Zealand, over a 43-month period (1 October 1997 - 30 April 2001) were retrospectively analyzed (the data having been prospectively collected). All cases of colorectal carcinoma during the period 1 October 1997 - 30 July 2001 (3 months longer, to capture delayed diagnoses) were also identified. The two databases were then compared, and all cases in which a colonoscopy had been performed more than 6 weeks before a colorectal carcinoma specimen being received by the pathology department were identified and analyzed. RESULTS: A total of 5055 colonoscopies were undertaken in 4598 patients. Over this period, 630 colorectal carcinomas were identified in the pathology database; 286 of the patients affected were in the colonoscopy and pathology database. Sixty-six patients had had a colonoscopy performed more than 6 weeks before the diagnosis of colorectal carcinoma. Carcinoma was identified in 48 of these 66 patients, and management was being provided. Seventeen cancers (5.9 %) were missed at colonoscopy, and the patients had had an incomplete colonoscopy in nine of these cases. In seven of the 17, an alternative benign cause was recorded. In four patients, a lesion was seen and thought to be benign, although subsequently proven not to be. In another four cases, the cancer was not diagnosed despite adequate bowel preparation and what was thought by the colonoscopist to be an adequate colonoscopy. CONCLUSIONS: Colonoscopy missed 17 of 286 cancers (5.9 %). The reasons why cancers were missed relate to incomplete colonoscopy, poor bowel preparation, misinterpretation of what was seen, failure to carry out adequate biopsy (and follow-up) of lesions seen, and systems failures related to follow-up investigations in patients who had an incomplete colonoscopy. The fact that colonoscopy and barium enema investigations may fail to diagnose cancers has important medicolegal implications. The recognition that colonoscopy may miss a cancer should encourage doctors to reinvestigate patients when there is a lack of correlation between the clinical and investigative findings.

Management of late complications of pelvic radiation in the rectum and anus: a review.

PURPOSE: Radiotherapy has become one of the most important treatment modalities for human malignancy. Tumors affecting the organs of the pelvis are increasingly being irradiated for local treatment benefit, with the subsequent complication of anorectal injury of varying extent. The aim of this review is to determine how to manage the consequences of long-term effects of radiotherapy on the rectum and anus. METHODS: A comprehensive search of the literature with manual cross-referencing was performed using the MEDLINE, PubMed, and Cochrane Databases. RESULTS: Long-term manifestations of injury caused by pelvic radiotherapy include abscess and fistula formation, stricture, mucus discharge, urgency, tenesmus, diarrhea, increased risk of cancer, and most commonly, bleeding. Most patients present with several symptoms; however, usually one symptom dominates. CONCLUSIONS: Many of these symptoms are self-limiting, and mucosal complications may often be treated by nonsurgical methods such as topical formalin application, endoscopic argon plasma coagulation, and hyperbaric oxygen therapy. Conservative measures have not been shown to be of benefit if symptoms persist. Structural abnormalities and septic complications are likely to require surgery. Modern techniques in the delivery of radiotherapy help minimize the likelihood of rectal complications.

Does human papilloma virus have a role in squamous cell carcinoma of the colon and upper rectum?

AIM: To determine if Human Papilloma Virus (HPV) has a role in the aetiology of adenosquamous and squamous cell carcinoma of the colon and upper rectum, and to describe the clinical features seen in our patients with this condition. METHODS: Patients were identified with squamous cell carcinoma (SCC), adenosquamous carcinoma (Ad-SCC), or adenocarcinoma with squamous metaplasia (AA) of the colon and upper rectum over the 10 years from 1/1/1990 to 31/12/1999. Patients were identified from a prospective pathology database. All tumours were at least 5cm above the dentate line. Pathology blocks were stained using the Peroxidase labelled Streptavidin technique using mouse monoclonal antibody NCL-HPV-4C4, which identifies HPV 6, 11, 16 and 18. Age, gender and site matched controls (colorectal adenocarcinomas) were also stained. The clinical presentation and management was reviewed from the case notes. RESULTS: Twenty patients were identified from a pathological database of 2351 colorectal cancers (0.85% of colorectal cancers). 0/20 of the study patients (SCC, Ad-SCC, AA) or adenocarcinoma controls stained positively for HPV 6, 11, 16, 18. The clinical presentation was similar to patients presenting with adenocarcinomas. CONCLUSIONS: The peroxidase labelled streptavidin technique is an immunohistochemical technique with high specificity but lower sensitivity. There was no apparent association between HPV 6, 11, 16, 18 and squamous cell and adenosquamous carcinoma of the colon and rectum using this technique. Clinical features are similar in squamous and adenosquamous colorectal carcinomas to colorectal adenocarcinomas.