Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn's disease patients.

Objectives: Anti-TNF agents are effective to treat perianal Crohn's disease (CD). Evidence suggests that Crohn's disease patients with perianal fistulas need higher infliximab (IFX) serum concentrations compared to patients without perianal CD to achieve complete disease control. Our aim was to compare anti-TNF serum concentrations between patients with actively draining and closed perianal fistulas. Methods: A retrospective survey was performed in CD patients with perianal disease treated with IFX or adalimumab (ADL). Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging. Results: We identified 66 CD patients with a history of perianal fistulas treated with IFX (n = 47) and ADL (n = 19). Median IFX serum trough concentrations ([interquartile range]) were higher in patients with closed fistulas (n = 32) compared to patients with actively draining fistulas (n = 15): 6.0 µg/ml [5.4-6.9] versus 2.3 µg/ml [1.1-4.0], respectively (p < .001)). A similar difference was seen in patients treated with ADL: median serum concentrations were 7.4 µg/ml [6.5-10.8] in 13 patients with closed fistulas versus 4.8 µg/ml [1.7-6.2] in 6 patients with producing fistulas (p = .003). Serum concentrations of ≥5.0 µg/ml for IFX (area under the curve of 0.92; 95% CI: 0.82-1.00)) and 5.9 µg/ml for ADL (area under the curve of 0.89; 95% CI 0.71-1.00) were associated with fistula closure. Conclusion: Cut-off serum concentrations ≥5.0 µg/ml for IFX and ≥5.9 µg/ml for ADL were associated with perianal fistula closure. Hence, patients with producing perianal fistulas may benefit from anti-TNF dose intensification to achieve fistula closure.

Role of interleukin-17 in the pathogenesis of perianal abscess and anal fistula: a clinical study on 50 patients with perianal abscess.

BACKGROUND: To investigate the role of interleukin (IL)-17 in tissue and peripheral blood of perianal abscess and anal fistula. METHODS: Patients with primary perianal abscess (n = 50) admitted to Jinhua Municipal Central Hospital between March 2003 and August 2004 were enrolled. Fifty patients with mixed haemorrhoids, who showed no perianal abscess or anal fistula, were also recruited as the control. After surgery, patients were followed up for 6 months. Protein and gene expression of IL-17 was determined in surgically harvested anal tissues and peripheral blood, respectively. The relationship between IL-17 and clinical pathological features were analysed. RESULTS: As shown by immunohistochemistry of anorectal tissues, the positive rate of IL-17 protein was higher in the perianal abscess group than in the control group. In patients with perianal abscess, the expression of IL-17 significantly correlated with the diameter of the abscess (P = 0.013), the wound surface healing time (P = 0.010) and the progression into anal fistula (P = 0.003). For the gene expression of IL-17 in peripheral blood cells, the level was significantly higher in patients with perianal abscess comparing to the control group (0.4350 ± 0.1190 versus 0.1785 ± 0.1230, P ≤ 0.001). Comparing to the recovery group, patients with their perianal abscess progressed to anal fistula showed higher levels of IL-17 gene expression (P = 0.014). CONCLUSIONS: Expression of IL-17 was increased in the anorectal tissues and peripheral blood of patients with perianal abscess and anal fistula. IL-17 may play an important role in the pathogenesis of perianal abscess and anal fistula.

Higher Postinduction Infliximab Serum Trough Levels Are Associated With Healing of Fistulizing Perianal Crohn's Disease in Children.

Background: There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24. Methods: In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula healing. Results: A total of 667 children with Crohn's disease were recruited, with 85 (12.7%) patients diagnosed with fistulizing PCD. There were 27 of 52 (52%) children in whom pre-fourth infusion IFX levels were measured (mean age, 12.57 ± 5.12 years). At week 24, 14 of 27 (52%) patients responded with healing/healed PCD, whereas the rest had ongoing active fistulizing disease. The median IFX pre-fourth dose level in the responders was 12.7 ug/mL, compared with 5.4 ug/mL in the active disease group (P = 0.02). There was a strong correlation between IFX levels and healing of fistulizing PCD at week 24 (r = 0.65; P < 0.001). The AUROC was 0.80 (95% confidence interval, 0.64-0.97; P = 0.007) for pre-fourth IFX level to predict response of fistulizing PCD at week 24, and a level of 12.7 ug/mL best predicted fistula healing. Conclusions: Higher trough IFX levels are associated with healing of fistulizing perianal CD.

Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease.

BACKGROUND: Infliximab has been found to be efficacious in the treatment of fistulas in the setting of Crohn's disease, even though some patients do not benefit from therapy. AIM: To assess the correlation between perianal fistula healing and trough levels of infliximab. METHODS: In this cross-sectional study, we identified patients with Crohn's disease who had perianal fistulas and were treated with infliximab for at least 24 weeks. We excluded patients who underwent a faecal diversion procedure or proctectomy. Predictive variables included demographics, disease phenotype, disease activity, infliximab levels, anti-infliximab antibodies. The primary outcome was fistula healing defined as the absence of drainage. The secondary outcome was complete fistula closure and mucosal healing. RESULTS: 117 patients were included. Patients with fistula healing had significantly higher median serum infliximab levels when compared to those with active fistulas [15.8 vs. 4.4 µg/mL, respectively (P < 0.0001)]. There was an incremental gain in fistula healing with higher infliximab levels. The AUC for the association between fistula healing and infliximab levels was 0.82 (P < 0.0001), while the AUC for the association of infliximab levels and fistula closure was 0.69 (P = 0.014). Patients with anti-infliximab antibodies had a lower chance of achieving fistula healing (OR: 0.04 [95%CI: 0.005-0.3], P < 0.001). CONCLUSIONS: There is a significant association between serum infliximab levels and rates of fistula healing. Achieving infliximab levels ≥10.1 mcg/mL in patients with Crohn's disease and perianal fistulas may improve outcomes as part of a treat-to-target strategy.

[Applicability and indications of colonoscopic screening for Crohn's disease in patients with fistula-in-ano].

OBJECTIVE: To determine the indications of colonoscopic screening for Crohn's disease in patients with fistula-in-ano. METHODS: Clinical data of 302 patients with perianal fistula who received colonoscopy examination from January 2010 to December 2013 in the Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University were analyzed retrospectively. Parameters for differentiating perianal Crohn's disease from nonspecific fistulae were screened by logistic regression analysis. A regression mathematical model was established for the prediction of perianal Crohn's disease. RESULTS: A total of 302 patients received colonoscopy examination, and Crohn's disease was found in 16 patients (CD group). Results of univariate analysis on 26 parameters of clinical manifestation, laboratory and radiological examination revealed that differences in 11 clinical parameters between the CD group and non-CD group were statistically significant(all P<0.05), including age, BMI, abdominal pain, non-specific symptoms, multiple fistula, complex anal fistula, neutrophil count, platelet count, activated partial thromboplastin time, hemoglobin concentration and serum albumin concentration. Multivariate analysis revealed that age≤40 years (OR=14.464, 95% CI: 1.143-183.053, P=0.039), BMI<24.0 kg/m2 (OR=8.220, 95% CI:1.005-67.200, P=0.049), abdominal pain (OR=13.148, 95% CI: 1.110-155.774, P=0.041), complex anal fistula (OR=7.056, 95% CI:1.166-42.688, P=0.033) and elevated platelet count (OR=1.012, 95% CI: 1.004-1.0194, P=0.003) were independent risk factors for discovery of Crohn's disease by colonoscopy. Area under the ROC curve of the regression mathematical model based on factors mentioned above was 0.921, indicating that the model was highly predictive. The sensitivity and specificity of this model was 81.3% and 86.7% respectively when the optimal diagnostic cut-off point was established at 0.856. CONCLUSIONS: Parameters that predict Crohn's disease in patients with perianal fistula include age, BMI, abdominal pain, classification of fistula and platelet count. Colonoscopy is recommended for patients at high risk.

Increase of serum C-reactive protein is an early indicator of subsequent symptomatic anastomotic leakage after anterior resection.

OBJECTIVE: This prospective study investigated the factors which might indicate anastomotic leakage after low anterior resection. METHOD: Thirty-three patients who underwent anterior resection for rectal carcinoma (n = 32) and severe dysplasia (n = 1), were monitored daily by serum C-reactive protein (CRP) and white blood cell count (WBC) estimations until discharge from hospital. Computed tomography (CT) scans were performed on postoperative days 2 and 7 and the amount of presacral fluid collection was assessed. All patients had a pelvic drain and the volume of drainage was measured daily. RESULTS: The level of the anastomosis was at a median 5 cm (3-12 cm) above the anal verge. There was no 30-day mortality. Nine (27.2%) of the 33 patients developed a symptomatic anastomotic leakage which was diagnosed at a median of 8 days (range 4-14) postoperatively. The serum CRP was increased in patients who leaked from postoperative day 2 onwards (P = 0.004 on day 2; P < 0.001 on day 3-8). The WBC was decreased in preoperatively irradiated patients on days 1-5 (P

Gender differences in incidence of idiopathic fistula-in-ano are not explained by circulating sex hormones.

The observed increased incidence of idiopathic anal fistulae in men compared with women cannot be explained by the cryptoglandular hypothesis alone. Male predilection is even more pronounced in neonates and is also seen in the canine population. Investigations into hormonal aspects of hidradenitis suppurativa suggest a possible influence of androgens in its pathogenesis. In order to investigate the possibility of a similar effect in fistula-in-ano, we have compared a range of circulating sex hormones in 15 male and 12 female patients with anal fistulae with those in equal numbers of age-matched controls. There were no differences in levels of any measured hormones between male patients and healthy controls. There was no evidence of increased androgenisation of female patients. Women with fistulae had higher levels of circulating oestradiol (253 vs 163 pmol/l, medians, P = 0.03) and lower levels of progesterone (1.05 vs 3.0 nmol/l, medians, P = 0.039) than healthy women. Further work is merited to investigate the possibility of increased local androgen conversion in anal glands.

Abscesos y fístulas perianales: experiencia de 111 casos en dos Hospiales del Oeste de Caracas / Perianal abscess and fistula: experience of 111 cases in Caracas' west side

Se presenta la experiencia de 111 casos de abscesos y fístulas perianales tratados en dos hospitales del oeste de la Zona Metropolitana de Caracas: Hospital General del Oeste "José Gregorio Hernandez" (HGO) y Hospital "Dr. Ricardo Barquero González" (HRBG), En un período de 12 años (1982-1993). Se hace énfasis en el origen criptoglandular de estas entidades y la relación anátomoclínica existente entre ambas, así como la frecuencia del antecedente de patología anal previa en estos pacientes. La sintomatología signología se derivan de la región perianal. El tratamiento más utilizado en la fase aguda fué el drenaje del absceso y en la fase crónica la fistulotomía. La fistulotomía anal primaria sólo se realizó en 7 pacientes (6,3 por ciento) pacientes, todos del HRBG. Se concluye la necesidad de realizar este ultimo procedimiento con mayor frecuencia debido al bajo porcentaje de recurrencias obtenidas en el HRBG durante los procedimientos de drenaje acompañados de fistulotomía primaria (10,5 por ciento de abscesos y 5,2 por ciento de fístulas) en comparación con el HGO (34,6 por ciento de abscesos y 15,3 por ciento de fístulas) donde no se realizaron fistulotomías anales primarias

Zinc deficiency as a problem in patients with Crohn's disease and fistula formation.

Zinc deficiency is common in patients with Crohn's disease (CD), especially in those with skin lesions and growth retardation. Patients with fistulas have been considered to be another group with zinc deficiency. We therefore determined serum zinc concentrations of 50 patients with CD. Zinc deficiency was diagnosed in 17 out of 50 patients (34%). Serum zinc concentrations of patients with fistulas were significantly lower than those of patients without fistulas, and zinc deficiency was found in 11/17 (65%) patients. Zinc deficiency may play a role in the formation and clinical course of fistulas. Therefore, in view of possible therapeutic implications, determination of serum zinc concentration in patients with CD and fistulas appears to be of value.

[Changes in blood serum proteins and blood electrolytes in patients with rectal fistulas and hemorrhoids]. / Izmeneniia belkov syvorotki i elektrolitov krovi u bol'nykh so svishchami priamoi kishki i gemorroem

Changes in blood serum and electrolytes were studied in 113 patients with rectal fistulas and hemorrhoid. The data obtained provided the opportunity for estimating objectively the intensity of inflammatory and destructive processes in pararectal cellular tissue.

Rectal lymphogranuloma venereum in Jamaica

Lymphogranuloma venereum is a major public health problem in Jamaica. With improvement in the standard of living, better housing, better general education, a healthier sex education, and a more active programme of venereal disease control, the incidence of rectal lymphogranuloma should diminish. The early diagnosis and treatment of the proctocolitis by drugs is effective and should reduce the incidence of stricture. Major operations should be reserved for cases in which the more conservative methods of treatment are unlikely to succeed or have failed. At present, in Jamaica, operation necessitating a permanent colostomy should be considered more carefully than in this country. Unfortunately our attempts to eradicate the disease by operation and leave the patient with a functioning anus have been attended with only very limited success. Some of the failures may be attributed to insufficent experience with these operations, but involvement of the sphincter in the dense fibrotic process is probably responsible for the majority. In these fibrotic sphincters functional control is impossible. In a small number of cases intra-sphincter proctectomy in one stage by the method described by Dimitrui and Gregoresco (1933) has given promising results where the sphincter is free. The disease appears to be self-limiting. There has been no evidence of reactivation after removal of the affected gut even though this is rarely a complete en bloc excision or indeed even after colostomy only. Our follow up has been short. I have deliberately avoided the term "cure" because rarely has the compliment fixation reaction been reversed to negative. The significance of a persistently positive serological reaction in the absence of clinical evidence of disease is yet to be assessed. We have come a long way since John Hunter described the bubo 175 years ago and Frei placed the study of the disease on a firm aetiological basis 140 years later. In the past 35 years our knowledge of the lympho-granuloma venereum virus has increased, but the problem of treatment of rectal stricture, the most disabling complication of the disease, awaits solution. Morte (1933) stated: "The study of the stricture of the rectum is as fascinating as the treatment is discouraging. " In 1960 we can say: "Treatment of rectal stricture is often disappointing, but the results are encouraging" (Summary)