Slowly cutting, loose seton ligature and staged fistulotomy for healing of idiopathic perianal fistula and influence on anal continence.

PURPOSE: To investigate the ability of a "slowly cutting, loose seton ligature and staged fistulotomy" to heal perianal fistulas, the time needed with the seton ligature, recurrence rate, influence on anal continence, health-related quality of life (HRQoL), and patient satisfaction. METHODS: Observational single-center study. We reviewed the medical records of all patients with primary surgeries from January 1, 2009, to December 31, 2018. The patients answered a questionnaire pre- and postoperative on anal continence (St. Mark's incontinence score) and HRQoL (The Short Health Scale). Satisfaction with the operation was answered postoperatively. RESULTS: Forty-three patients (37 men, 6 women) were included. Initially 41 of 43 healed (95%). Three patients (7%) had a recurrence, two healed after retreatment. The median follow-up was 55 months (IQR, 4). Thirty-four patients (79%) responded to the questionnaire. At follow-up, forty (93%) patients were healed. The median time treated with a seton ligature in the healed patients was 13 months (IQR, 14). St. Mark's incontinence score preoperative was median 2 (IQR, 9) and after the operation median 1 (IQR, 4). The Short Health Scale improved from median 20 (IQR, 5) preoperatively to 5 (IQR, 5) postoperatively, p < 0.001. Patient satisfaction was median 1 (= very satisfied) (IQR, 1). CONCLUSION: A "slowly cutting, loose seton ligature followed by a staged fistulotomy", heals the vast majority of perianal fistulas with minor or none influence on continence and few recurrences. Patient-reported HRQoL improves greatly, and patient satisfaction is high.

Quality of life in patients with hemorrhoidal disease.

Background: Operation for hemorrhoidal disease is one of the most common operations performed globally. However, we know little about the impact of the disease on health-related quality of life (HRQoL), or the importance of the observed clinical and anatomical changes. Method: This was a single-center cross-sectional and cohort study. HRQoL was assessed using the Short Form 12 and 36 (SF12 and SF36), EuroQoL 5-dimensions 5-levels (EQ-5D), and a disease specific questionnaire; Short Health Scale for Hemorrhoidal Disease (SHSHD). SF12 and EQ-5D scores in 257 patients with symptomatic hemorrhoids referred to our proctologic outpatient clinic were compared to a Danish background population adjusting for age, gender, body mass index and educational status.Symptoms were assessed using the Hemorrhoidal Disease Symptom Score. The anatomical pathology was graded using Goligher's classification. The associations between clinical characteristics and HRQoL were tested. The impact of surgical treatment was assessed in 111 patients followed one year postoperatively. Results: Patients reporting a high symptom load had lower SF12 physical health scores compared with the background population. The EQ-5D indexes indicated impaired HRQoL in men, women <50 years and patients with higher education. Improvements in all three HRQoL measures were seen after surgery.Symptom burden had a negative association with HRQoL measures, whereas the surgeon's grading of anatomical pathology had no association. Conclusion: Hemorrhoidal disease has a negative impact on HRQoL related to the degree of symptoms. Surgical treatment improve the QoL. The surgeon's grading of anal pathology had no association with QoL.

Making Use of Patient-Reported Outcome Measures for Haemorrhoidal Disease in Clinical Practice: A Perspective.

Haemorrhoidal disease (HD) affects millions of people around the world and for most it is a recurring problem. Increasingly, clinicians broaden their focus on the patient's experiences with haemorrhoidal symptoms, including their impact on daily life. The patient's experience can be assessed using a patient-reported outcome measure (PROM). A PROM facilitates a deeper understanding of the disease-burden and allows a clinician to obtain information directly from the patients about their experiences with the ailment. Over the last years, PROMs have shown their additional role to traditional outcomes for several diseases and have earned their place in the daily consultation room. In order to improve and personalize the treatment of HD, we endorse the use of validated PROMs in clinical care.

Minimal Open Hemorrhoidectomy Versus Transanal Hemorrhoidal Dearterialization: The Effect on Symptoms: An Open-Label Randomized Controlled Trial.

BACKGROUND: There is limited evidence on the long-term efficacy of transanal hemorrhoidal dearterialization compared with hemorrhoidectomy. Most studies investigated short-term effects with postoperative pain as the primary outcome. Being a benign disease, the long-term goal of treatment for hemorrhoids is the resolution of symptoms and improvement of quality of life. OBJECTIVE: The purpose of this study was to compare the effect of minimal open hemorrhoidectomy versus transanal hemorrhoidal dearterialization on patient-reported symptoms. DESIGN: This was an open-label randomized controlled trial. SETTINGS: This was a single-center study. PATIENTS: Patients with symptomatic hemorrhoids grade II to IV (Goligher's classification) were included. INTERVENTIONS: Patients were randomly allocated to minimal open hemorrhoidectomy or transanal hemorrhoidal dearterialization. MAIN OUTCOME MEASURES: The primary outcome was symptoms assessed by the Hemorrhoidal Disease Symptom Score 1 year postoperatively. Secondary outcomes included health-related quality of life, patient satisfaction, postoperative pain and recovery, adverse events, recurrence, and hospital costs. RESULTS: Forty-eight patients received minimal open hemorrhoidectomy, and 50 patients received transanal hemorrhoidal dearterialization. No difference in symptom score at 1-year follow-up was found. Median (range) symptom score was 3 (0-17) after minimal open hemorrhoidectomy and 5 (0-17) after transanal hemorrhoidal dearterialization (median difference = -1.0 (95% CI, -3.0 to 0.0); p = 0.15). Residual hemorrhoidal prolapse was reported more frequently (p = 0.008), and more patients had treatment for recurrence after transanal hemorrhoidal dearterialization (7 vs 0 patients; p = 0.013). Patient satisfaction was higher after minimal open hemorrhoidectomy (p = 0.049). No differences were found in the impact on health-related quality of life, average and peak postoperative pain, recovery, or adverse events (p > 0.05). Transanal hemorrhoidal dearterialization was more expensive (median difference = &OV0556;555 (95% CI, &OV0556;472-&OV0556;693); p < 0.001). LIMITATIONS: No blinding was included in this study. CONCLUSION: No difference was found in symptom score 1 year postoperatively. Minimal open hemorrhoidectomy had a better effect on the hemorrhoidal prolapse and higher patient satisfaction. More patients needed treatment for recurrence after transanal hemorrhoidal dearterialization. Minimal open hemorrhoidectomy has an immediate postoperative course similar to transanal hemorrhoidal dearterialization. See Video Abstract at http://links.lww.com/DCR/B152. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02061176. HEMORROIDECTOMíA MíNIMA ABIERTA VERSUS DESARTERIALIZACIóN HEMORROIDAL TRANSANAL: EL EFECTO SOBRE LOS SíNTOMAS: UN ESTUDIO ABIERTO CONTROLADO Y ALEATORIZADO: Hay evidencia limitada sobre la eficacia a largo plazo de la desarterialización hemorroidal transanal en comparación con la hemorroidectomía. La mayoría de los estudios han investigado los efectos a corto plazo con el dolor postoperatorio como el resultado primario. Al ser una enfermedad benigna, el objetivo a largo plazo del tratamiento de la enfermedad hemorroidal es la resolución de los síntomas y la mejora en la calidad de vida.Comparar el efecto de la hemorroidectomía abierta mínima versus la desarterialización hemorroidal transanal en los síntomas reportados por el paciente.Ensayo controlado aleatorizado abierto.Estudio en sede única.Pacientes con enfermedad hemorroidal sintomática de grado II-IV (clasificación de Goligher).Los pacientes fueron asignados aleatoriamente a hemorroidectomía mínima abierta o desarterialización hemorroidal transanal.El resultado primario fueron los síntomas evaluados por el Score de Síntomas de Enfermedad Hemorroidal un año después de la operación. Los resultados secundarios incluyeron calidad de vida relacionada con la salud, satisfacción del paciente, dolor y recuperación postoperatorios, eventos adversos, recurrencia y costos hospitalarios.Cuarenta y ocho pacientes recibieron hemorroidectomía abierta mínima y cincuenta pacientes recibieron desarterialización hemorroidal transanal. No se encontraron diferencias en la puntuación de los síntomas al año de seguimiento. La puntuación mediana (rango) de síntomas fue 3 (0-17) después de una hemorroidectomía mínima abierta y 5 (0-17) después de la desarterialización hemorroidal transanal (diferencia mediana [IC95%]: -1.0 [-3.0-0.0], p = 0.15). El prolapso hemorroidal residual se informó con mayor frecuencia (p = 0.008) y más pacientes recibieron tratamiento por recurrencia después de la desarterialización hemorroidal transanal (7 frente a 0 pacientes, p = 0.013). La satisfacción del paciente fue mayor después de una hemorroidectomía abierta mínima (p = 0.049). No se encontraron diferencias en el impacto sobre la calidad de vida relacionada con la salud, el dolor postoperatorio promedio y máximo, la recuperación o los eventos adversos (p> 0.05). La desarterialización hemorroidal transanal fue más costosa (diferencia mediana [IC95%]: &OV0556; 555 [472-693], p <0.001).Estudio sin cegamiento.No se encontraron diferencias en la puntuación de los síntomas a un año después de la operación. La hemorroidectomía mínima abierta tuvo un mejor efecto sobre el prolapso hemorroidal y una mayor satisfacción del paciente. Más pacientes necesitaron tratamiento para la recurrencia después de la desarterialización hemorroidal transanal. La hemorroidectomía abierta mínima tiene un curso postoperatorio inmediato similar a la desarterialización hemorroidal transanal. Consulte Video Resumen en http://links.lww.com/DCR/B152. (Traducción-Dr. Jorge Silva Velazco).ClinicalTrials.gov Identifier: NCT02061176.

Hemorrhoidal Disease Symptom Score and Short Health ScaleHD: New Tools to Evaluate Symptoms and Health-Related Quality of Life in Hemorrhoidal Disease.

BACKGROUND: There are no adequately validated tools to evaluate symptoms or disease-specific health-related quality of life in hemorrhoidal disease. OBJECTIVE: The purpose of this study was to assess validity, reliability, and responsiveness of a symptom score of patient-reported pain, itching, bleeding, soiling, and prolapse (Hemorrhoidal Disease Symptom Score). In addition, the study set out to assess reliability and responsiveness of an instrument to measure health-related quality of life in patients with hemorrhoids (Short Health ScaleHD), with 1 item in its 4 dimensions: symptom load, functional status, disease-specific worries, and general well-being. DESIGN: This was a cross-sectional (validity and reliability) and longitudinal (responsiveness) study. SETTINGS: The study was conducted at a single center. PATIENTS: Cohort 1 included 295 patients with hemorrhoids to study validity and 60 patients with test-retest scores to study reliability. Cohort 2 included 128 and 121 patients operated for hemorrhoids to study responsiveness of the Hemorrhoidal Disease Symptom Score and the Short Health ScaleHD. MAIN OUTCOME MEASURES: The study evaluated validity, reliability, and responsiveness. Patient-reported symptom load on a 7-point Likert scale was used as comparator, and receiver operating characteristics curve assessed discriminative validity. Interclass correlation assessed reliability. Receiver operating characteristics curve assessed responsiveness, meaning the ability to discriminate between patients with and without improvement after surgery. RESULTS: The Hemorrhoidal Disease Symptom Score demonstrated the ability to discriminate between patients reporting high or low symptom load (area under the curve = 0.786 (95% CI, 0.725-0.848)). The Hemorrhoidal Disease Symptom Score and the Short Health ScaleHD demonstrated adequate reliability and responsiveness, with interclass correlation of 0.822 (95% CI, 0.715-0.891) and 0.763 (95% CI, 0.634-0.851) and area under the curve of 0.843 (95% CI, 0.756-0.929) and 0.840 (95% CI, 0.752-0.929). LIMITATIONS: We had no gold standard comparator to assess validity and responsiveness. CONCLUSIONS: The findings suggest that the Hemorrhoidal Disease Symptom Score is valid, reliable, and responsive and that the Short Health ScaleHD is reliable and responsive. Used together, these tools provide a good overview of symptoms and their impact on patient well-being. See Video Abstract at http://links.lww.com/DCR/A770.

The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohn's Disease.

BACKGROUND AND AIMS: The importance of efficient and safe treatment of Crohn's disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohn's disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohn's disease. METHODS: Thirty-six patients from seven hospitals with primary ileocaecal Crohn's disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohn's disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. RESULTS: There were no differences between the treatment groups in Crohn's disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t=erminated prematurely. CONCLUSION: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

Increased risk of post-operative complications in patients with Crohn's disease treated with anti-tumour necrosis factor α agents - a systematic review.

INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based on these studies did not agree. The objective of this study was to review data from present reviews and meta-analyses in an attempt to come to conclusions for the use of anti-TNF-α in Crohn's disease patients in clinical practice. METHODS: Literature search using both electronic and manual searches was conducted according to a pre-defined protocol. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied. RESULTS: Two systematic reviews and six meta-analyses were found. Meta-analyses that included a large number of patients and applied quality assessment showed an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after abdominal surgery.

Can new inflammatory markers improve the diagnosis of acute appendicitis?

BACKGROUND: The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new inflammatory markers for improving the diagnosis of appendicitis. METHODS: The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients with suspected appendicitis by uni- and multivariable regression models. RESULTS: Of the new inflammatory variables, SAA, MPO, and MMP9 were the strongest discriminators for all appendicitis (receiver operating characteristics [ROC] 0.71) and SAA was the strongest discriminator for advanced appendicitis (ROC 0.80) compared with defence or rebound tenderness, which were the strongest traditional discriminators for all appendicitis (ROC 0.84) and the WBC count for advanced appendicitis (ROC 0.89). CCL2 was the strongest independent discriminator beside the AIR score variables in a multivariable model. The AIR score had an ROC area of 0.91 and could correctly classify 58.3 % of the patients, with an accuracy of 92.9 %. This was not improved by inclusion of the new inflammatory markers. CONCLUSION: The conventional diagnostic variables for appendicitis, as combined in the AIR score, is an efficient screening instrument for classifying patients as low-, indeterminate-, or high-risk for appendicitis. The addition of the new inflammatory variables did not improve diagnostic performance further.

The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease: a systematic review.

BACKGROUND: Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications. OBJECTIVE: We assessed the effect of anti-tumor necrosis factor alpha on postoperative complications in patients with Crohn's disease undergoing abdominal surgery. DATA SOURCES: Studies were identified through electronic and manual searches. STUDY SELECTION: Observational studies on patients with Crohn's disease undergoing laparoscopic or open abdominal surgery were included. INTERVENTIONS: Anti-tumor necrosis factor alpha agents were administered within 3 months before surgery. MAIN OUTCOME MEASURES: The primary outcome was anastomotic complications including overt dehiscence, intra-abdominal abscess, and enteric fistulas. RESULTS: Fourteen studies on 679 patients in the intervention (anti-tumor necrosis factor alpha) group and 2363 controls were included. Random-effects meta-analysis found no difference in anastomotic complications between the 2 groups (7.6% versus 8.2%; risk ratio, 0.91; 95% CI, 0.56-1.48). There was clear heterogeneity between studies. In subgroup analyses, the anti-tumor necrosis factor alpha increased anastomotic complications in trials with a lower risk of bias, but not in the studies with a higher bias risk (risk ratio, 1.63; 95% CI, 1.03-2.60 and risk ratio, 0.17; 95% CI, 0.05-0.60). In the overall analysis and in studies with a lower bias risk, anti-tumor necrosis factor alpha agents increased the risk of nonanastomotic surgical complications, major medical complications, and minor medical complications. LIMITATIONS: Limitations of observations studies. CONCLUSIONS: In studies with a low risk of bias, anti-tumor necrosis factor alpha agents increased the risk of anastomotic complications. Inadequate bias control may lead to an underestimated risk of anastomotic complications.

Biologic treatment or immunomodulation is not associated with postoperative anastomotic complications in abdominal surgery for Crohn's disease.

OBJECTIVES: There are concerns that biologic treatments or immunomodulation may negatively influence anastomotic healing. This study investigates the relationship between these treatments and anastomotic complications after surgery for Crohn's disease. PATIENTS AND METHODS: Retrospective study on 417 operations for Crohn's disease performed at four Danish hospitals in 2000-2007. Thirty-two patients were preoperatively treated with biologics and 166 were on immunomodulation. In total, 154 were treated with corticosteroids of which 66 had prednisolone 20 mg or more. RESULTS: Anastomotic complications occurred at 13% of the operations. There were no difference in patients on biologic treatment (9% vs. 12% (p = 0.581)) or in patients on immunomodulation (10% vs. 14% (p = 0.263)). Patients on 20 mg prednisolone or more had more anastomotic complications (20% vs. 11% (p = 0.04)). Anastomotic complications were more frequent after a colo-colic anastomosis than after an entero-enteric or entero-colic (33% vs. 12% (p = 0.013)). Patients with anastomotic complications were older (40 years vs. 35 years (p = 0.014)), had longer disease duration (7.5 years vs. 4 years (p = 0.04)), longer operation time (155 min vs. 115 min (p = 0.018)) and more operative bleeding (200 ml vs. 130 ml (p = 0.029)). Multivariate analysis revealed preoperative treatment with prednisolone 20 mg or more, operation time and a colo-colic anastomosis as negative predictors of anastomotic complications. CONCLUSIONS: Preoperative biologic treatment or immunomodulation had no influence on anastomotic complications. The study confirms previous findings of corticosteroids and a colo-colic anastomosis as negative predictors and also that surgical complexity, as expressed by bleeding and operation time, may contribute to anastomotic complications.

Systemic Th17-like cytokine pattern in gangrenous appendicitis but not in phlegmonous appendicitis.

BACKGROUND: Increasing circumstantial evidence suggests that not all patients with appendicitis will progress to perforation and that appendicitis that resolves may be a common event. Based on this theory and on indications of aberrant regulation of inflammation in gangrenous appendicitis, we hypothesized that phlegmonous and gangrenous appendicitis are different entities with divergent immunoregulation. METHODS: Blood samples were collected from patients with gangrenous appendicitis (n = 16), phlegmonous appendicitis (n = 21), and nonspecific abdominal pain (n = 42). Using multiplex bead arrays, we analyzed a range of inflammatory markers, such as interleukin (IL)-1ra, IL-1rbeta, IL-2, IL-6, IL-10, IL-12p70, IL-15, and IL-17; interferon-gamma; tumor necrosis factor; CXCL8; CCL2; CCL3; and matrix metalloproteinase (MMP)-1 MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13 in blood. RESULTS: Compared with patients with phlegmonous appendicitis and nonspecific abdominal pain, the patients with gangrenous appendicitis had increased levels of the proinflammatory markers IL-6, CCL2, IL-17, MMP-8, and MMP-9 (P < or = .04 each) accompanied by increased levels of the anti-inflammatory cytokines IL-1ra and IL-10 (P < or = .02). Patients with phlegmonous appendicitis had increased levels of IL-10 only. CONCLUSION: The finding of a pattern of inflammatory markers compatible with the highly inflammatory Th17 subset in sera from patients with gangrenous appendicitis, but not in phlegmonous appendicitis, supports the hypothesis that gangrenous and phlegmonous appendicitis are different entities with divergent immune regulation. Additional studies of the differential immunopathogenesis of phlegmonous and gangrenous appendicitis are warranted, as this may have important implications in the diagnosis and management of patients with suspicion of appendicitis.

Thiopurine therapy is associated with postoperative intra-abdominal septic complications in abdominal surgery for Crohn's disease.

PURPOSE: Thiopurines are important as maintenance therapy in Crohn's disease, but there have been concerns whether thiopurines increase the risk for anastomotic complications. The present study was performed to assess whether thiopurines alone, or together with other possible risk factors, are associated with postoperative intra-abdominal septic complications after abdominal surgery for Crohn's disease. METHODS: Prospectively registered data regarding perioperative factors were collected at a single tertiary referral center from 1989 to 2002. Data from 343 consecutive abdominal operations on patients with Crohn's disease were entered into a multivariate analysis to evaluate risk factors for intra-abdominal septic complications. All operations involved either anastomoses, strictureplasties, or both; no operations, however, involved proximal diversion. RESULTS: Intra-abdominal septic complications occurred in 26 of 343 operations (8%). Thiopurine therapy was associated with an increased risk of intra-abdominal septic complications (16% with therapy; 6% without therapy; P = 0.044). Together with established risk factors such as preoperative intra-abdominal sepsis (18% with sepsis; 6% without sepsis; P = 0.024) and colo-colonic anastomosis (16% with such anastomosis; 6% with other types of anastomosis; P = 0.031), thiopurine therapy was associated with intra-abdominal septic complications in 24% if any 2 or all 3 risk factors were present compared with 13% if any 1 factor was present, and only 4% in patients if none of these factors were present (P < 0.0001). CONCLUSIONS: Thiopurine therapy is associated with postoperative intra-abdominal septic complications. The risk for intra-abdominal septic complications was related to the number of identified risk factors. This increased risk should be taken into consideration when planning surgery for Crohn's disease.

Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease.

BACKGROUND: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. METHODS: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. RESULTS: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients; at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed. CONCLUSIONS: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery.

Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease.

OBJECTIVE: Recurrence of Crohn's disease (CD) after surgery is common. Azathioprine/6-mercaptopurine (Aza/6-MP) is effective in controlling medically induced remission but, so far, has only been sparsely investigated after surgically induced remission. This study comprises a subset of CD patients considered to have an aggressive disease course and chosen for treatment with Aza postoperatively. MATERIAL AND METHODS: In 1989-2000, a total of 100 patients with CD were given Aza/6-MP as a postoperative prophylaxis. Fourteen Aza/6-MP-intolerant patients were compared with 28 Aza-tolerant patients, matched for gender, age, and duration of disease. Patients were prospectively registered for symptoms using a modified Crohn's disease activity index (CDAI) and perceived health was assessed on a visual analogue scale (VAS). The primary outcome variable was the modified CDAI postoperatively integrated over time; other variables were time to first relapse (modified CDAI >or= 150), time to first repeated surgery, number of courses of steroids, and repeated surgery per year of follow-up. Patients were followed for a median of 84.7 months (23.2-140). RESULTS: The modified CDAI integrated over time was 93 for Aza-treated patients compared with 184 for controls (p=0.01) and time to first relapse was 53 and 24 months, respectively (p<0.05). Aza-treated patients needed fewer courses of corticosteroids (p=0.05) compared with controls. Perceived health did not differ between the groups, nor did need of repeated surgery. Time to first repeat operation was 53 and 37 months, respectively. CONCLUSIONS: In CD patients considered to have an aggressive disease course, Aza reduced symptoms after surgery and prolonged the time to symptomatic relapse. The findings support a role for Aza as a postoperative maintenance treatment in CD.

Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon.

OBJECTIVE: Studies of mucosal permeability to protein antigens in humans are limited to in vitro techniques. The use of surgical specimens for such studies has major shortcomings. Endoscopic biopsies in Ussing chambers have been introduced as a means of studying secretion and transepithelial permeability, but have not been evaluated for studies of protein antigen uptake in human intestine. MATERIAL AND METHODS: Standard forceps biopsies from the sigmoid colon of 24 healthy volunteers were mounted in Ussing chambers with an exposed tissue area of 1.76 mm2. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP; 45 kDa protein antigen) were used as permeability markers. Mucosal permeability, electrophysiology, histology and energy contents of the biopsies were studied over time. To evaluate the ability of the technique to detect permeability changes, the mucosa was modulated with capric acid, a medium-chain fatty acid, known to affect tight junctions. RESULTS: In the Ussing chamber the mucosal biopsies were viable for 160 min with stable levels of ATP and lactate, and only minor changes in morphology. Steady-state permeability with low variability was seen for both markers during the 30-90 min period. Exposure to capric acid induced a rapid decrease in short-circuit current (Isc) and a slower reversible decrease in transepithelial resistance (TER), as well as an increased permeability to 51Cr-EDTA and HRP. CONCLUSIONS: Endoscopic biopsies of human colon are viable in Ussing chambers and are reliable tools for studies of mucosal permeability to protein antigens. The technique offers a broad potential for studies of mucosal function in the pathophysiology of human gastrointestinal diseases.

[Enterocutaneous fistulas--persisting conditions but the healing capacity can be surgically restored. Current treatment and surgical skills reduce the mortality]. / Enterokutana fistlar--krävande tillstånd som kan opereras till läkning. Modern behandling och kirurgisk erfarenhet minskar mortaliteten.

Persisting enterocutaneous fistulae are difficult to treat. Mortality and morbidity are high. Patients are characterized by chronic infection, systemic inflammation, catabolism and impaired healing. During 1988-2002 69 patients were operated at the University Hospital, Linköping. The mortality was 18% in 1988 to 1996 but decreased to 7% in 1997 to 2002 after establishment of present treatment strategies. It's main feature is staged surgery rising ostomies rather than doing primary anastomoses. The ostomies are closed several months later when infection and systemic inflammation are overcome and nutrition and healing capacity are restored. All patients that survived healed their fistula after surgery. Open abdomen, high output fistulas, impaired liver function and a low serum albumin were associated with a poor prognosis for healing and mortality. Effective techniques for management of abdominal defects, methods to establish enteral nutrition, minimize chronic inflammation and liver impairment as well as operative techniques and strategies are important.

Increased anal resting pressure and rectal sensitivity in Crohn's disease.

PURPOSE: Anal pathology occurs in 20 to 80 percent of patients with Crohn's disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn's disease compared with healthy controls. METHODS: Twenty patients with Crohn's disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations. RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025). CONCLUSIONS: This study demonstrates how patients with Crohn's disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.

Appendectomy is followed by increased risk of Crohn's disease.

BACKGROUND & AIMS: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. METHODS: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. RESULTS: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. CONCLUSIONS: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.

Presence of eubacteria in biopsies from Crohn's disease inflammatory lesions as determined by 16S rRNA gene-based PCR.

The aim of this study was to search for putative microbial agents in Crohn's disease (CD) tissues by bacterial broad-range 16S rDNA PCR combined with genus- and species-specific DNA hybridisation analysis. Biopsies taken both surgically and endoscopically from the terminal ileum of 11 CD patients and 11 control patients were investigated. Significant amounts of eubacteria were demonstrated in biopsies taken endoscopically from both affected and unaffected individuals; the biopsies taken at surgery from control patients were negative. Three of five biopsies taken surgically from CD patients harboured Helicobacter spp.-, Mycobacterium paratuberculosis-, Listeria monocytogenes- and Escherichia coli-like 16S rDNA sequences. These findings show the importance of the sampling method chosen when combined with molecular typing of eubacteria in intestinal tissues. The mixed bacterial flora found in the surgical biopsies from CD patients supports the idea that the enteric microflora enters primary lesions where secondary bacterial colonisers may elicit a chronic inflammatory syndrome.