[Efficacy of over-the-scope clip for gastrointestinal fistula].

OBJECTIVE: To explore the efficacy of over-the-scope clip (OTSC) in the treatment of gastrointestinal fistula. METHODS: Clinical data of 12 gastrointestinal fistula patients, including 3 internal fistula and 9 external fistula treated with OTSC in our institute from March 2015 to May 2016 were retrospectively analyzed. OTSC was performed when pus was drained thoroughly and intra-abdominal infection around gastrointestinal fistula was controlled, and each patient received one clip to close fistula. RESULTS: There were 6 female and 6 male patients with mean age of (50.1±12.6) years. The successful rate of endoscopic closure was 100% without complications including bleeding and intestinal obstruction during and after OTSC treatment. According to comprehensive evaluation, including drainage without digestive juices, no recurrence of intra-abdominal infection, no overflow of contrast medium during digestive tract radiography, and CT examination without intra-abdominal abscess, clinical gastrointestinal fistula closure was 91.7%(11/12). There was no recurrence of gastrointestinal fistula during 3 months of follow-up in 11 patients. In the remaining 1 case, the gastric fistula after laparoscopic sleeve gastrectomy recurred one week after OTSC treatment because of intra-abdominal infection surrounding fistula, and was cured by surgery finally. CONCLUSION: The endoscopic closure treatment of OTSC for gastrointestinal fistula is successful and effective, and control of intra-abdominal infection around fistula with adequate drainage is the key point.

Effect of Oral ω3-Polyunsaturated Fatty Acids as a Complement Management to Control Fistula Output and Inflammation in Patients With Digestive Fistula.

BACKGROUND: The presence of digestive fistula involves chronic inflammation and fibrosis. It has been reported that ω3-polyunsaturated fatty acids stimulate the resolution of inflammation. AIM: Determine if the administration of oral ω3 reduces fistula output and the time required for fistula closure. METHODS: Forty-nine patients with postoperative fistula were randomly divided in two groups: 26 received conventional treatment and 23 received the conventional treatment supplemented with ω3 (540 mg eicosapentaenoic acid and 360 mg docosahexaenoic acid) for 35 days. Patients were monitored daily for fistula output and spontaneous closure. Additionally, serum pro-inflammatory cytokines and C-reactive protein were quantified in four patients with conventional and in seven patients with ω3 treatment. RESULTS: Patients with ω3 had significantly decreased fistula output from days 2 to 27, compared to control (p < 0.05). Spontaneous fistula closure was achieved in 15 patients (65%) in the ω3 group and in 14 (54%) in the control group. ω3-polyunsaturated fatty intake also decreased the serum concentrations of interleukin-6 and C-reactive protein (p < 0.05). CONCLUSIONS: Our results suggest that ω3 supplementation to conventional medical treatment decreases fistula output and reduces inflammation (interleukin-6 and C-reactive protein), and these effects may increase the efficiency of conventional medical treatment.

Therapeutic approach to Crohn disease: possible parallels with hidradenitis suppurativa. / Abordaje terapéutico de la enfermedad de Crohn: posibles paralelismos con la hidradenitis supurativa.

The current controversy in the setting of dermatology surrounding the treatment of inflammatory diseases, and specifically hidradenitis suppurativa, bears strong similarities with the debate concerning inflammatory bowel disease (IBD) that took place several years ago. That debate led to new perspectives on this disease and, in particular, its treatment after the development of biological agents.

Descripción epidemiológica y tratamiento de los pacientes con enfermedad de Crohn / Epidemiological description and treatment of Crohn's disease patients

Antecedentes: la enfermedad de Crohn es un proceso inflamatorio crónico granulomatoso que puede afectar todo el tracto digestivo. Se diagnostica cada vez más frecuentemente en nuestro medio, y es causa importante de morbimortalidad en los pacientes afectados. El presente estudio tiene como objetivo conocer la prevalencia de esta enfermedad, sus manifestaciones clínicas más frecuentes, los diversos tratamientos utilizados y la respuesta a estos. Métodos: se revisaron los expedientes clínicos de todos los pacientes con diagnóstico de enfermedad de Crohn evaluados durante 2009 en el Servicio de Gastroenterología de un centro de salud terciario, el Hospital "Dr. Rafael A. Calderón Guardia". Resultados: de un total de 28 pacientes con enfermedad de Crohn, solo tres casos fueron diagnosticados en la década 1990-2000, mientras que los restantes 25 casos fueron diagnosticados de 2001 a 2009. Un 60 por ciento de los casos diagnosticados corresponden a pacientes del sexo masculino. La población estudiada tiene una distribución de edades entre los 17 y 72 a¤os, con un promedio de edad de 39 años de edad. El 82 por ciento de los pacientes se encuentran con tratamiento de mantenimiento con base en derivados del ácido 5-aminosalicílico, mientras que un 62 por ciento también utiliza azatiprina, 6-mercaptopurina o metotrexate, un 51 por ciento reciben esteroides sistemáticos y solo siete pacientes recibieron inflimixab. Un 68 por ciento de los pacientes del presente estudio requirió manejo quirúrgico en algún momento de su evolución, y en un 96 por ciento de los pacientes se logró remisión de la enfermedad. Conclusión: la prevalencia de la enfermedad de Crohn parece encontrarse en aumento, y en los casos en los cuales hay fallo terapéutico al régimen farmacológico, puede ser necesario un abordaje quirúrgico...

Digestive system fistula: a problem still relevant today.

Digestive system fistula originates most frequently as a complication after surgical procedures, less often occurs in the course of inflammatory diseases, but it can also result from neoplasm and injuries. THE AIM OF THE STUDY was to analyze the causes and retrospectively assess the perioperative procedures as well as the results of digestive system fistula treatment. MATERIAL AND METHODS. Own experience in digestive system fistula treatment was presented. The subject group consisted of 32 patients treated at the General Surgery, Oncology and Endocrinology Clinical Department between 01.05.2005 and 30.04.2010 due to different digestive tract diseases. The causes of the occurrence of digestive system fistula, methods and results of treatment were analyzed. RESULTS. The analysis covered 32 patients with digestive system fistula, among them 15 men and 17 women. Average age for men was 57 years (20-78), and for women 61 years (24-88). In 11 patients idiopathic fistula causally connected with primary inflammatory disease (7 cases) and with neoplasm (4 cases) was diagnosed, in 19 patients fistula was the result of complications after surgery, in 2 - after abdominal cavity injury. Recovery from fistula was achieved in 23 patients (72%) with the use of individually planned conservative therapy (TPN, EN, antibiotics, drainage, and others) and surgery, depending on the needs of individual patient. 5 patients (16%) died, whereas in 4 left (12%) recovery wasn't achieved (fistula in palliative patients, with advanced stages of neoplasm - bronchoesophageal fistula, the recurrence of uterine carcinoma). CONCLUSIONS. Recently the results of digestive system fistula treatment showed an improvement which manifests itself in mortality decrease and shortening of fistula healing time. Yet, digestive system fistula as a serious complication still poses a very difficult surgical problem.

Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study.

BACKGROUND: Treatment options for fistulizing Crohn's disease (CD) are limited. AIM: To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. METHODS: Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. RESULTS: The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (≥50% closure at two consecutive post-baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. CONCLUSION: Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.

Efficacy and tolerability of immunoregulators and antibiotics in fistulizing Crohn's disease: a systematic review and meta-analysis of placebo-controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials was conducted to evaluate the efficacy and tolerability of two drug groups (immunoregulators and antibiotics) in the treatment of fistula in Crohn's disease (CD). METHODS: PubMed, Embase, Scopus, Google Scholar, and Web of Science were searched for clinical trial studies investigated the effects of immunoregulators and antibiotics in the treatment of fistulizing CD. Clinical response and adverse effects were the key outcomes of interest. Data were searched from the time period of 1966 through June 2010. RESULT: Eleven randomized placebo-controlled clinical trials that met our criteria (nine in different immunoregulators and two in antibiotics) were included in the analysis. Pooling of data showed that immunoregulators and antibiotics are significantly effective for at least a 50% reduction from baseline in the number of open actively draining fistulas with relative risk (RR) of 2.57 (95% CI of 1.55-4.25, P=0.0003) in four trials and 2.05 (95% CI of 1.03-4.08, P= 0.0414) in two trials respectively. The summary of RR for complete closure of fistulas in nine trials was 2.65 with a 95% CI of 1.66-4.22 and a significant RR (P < 0.0001). In regard to the tolerability, both immunoregulators and antibiotics showed insignificant adverse effects in comparison to placebo with an RR of 1.11 (95% CI of 0.96-1.27, P= 0.1513) and 0.6 (95% CI of 0.36-1, P= 0.0515), respectively and discontinuation because of these adverse effects in drug-treated groups was the same as placebo. Data about severe adverse effects were only available for immunoregulators that showed a significantly higher incidence when compared to placebo (RR= 2.24 with a 95% CI of 1.05-4.79; significant at P= 0.0374). CONCLUSION: This meta-analysis demonstrates the efficacy of immunoregulators and antibiotics in fistulizing CD. Regarding the safety, mild to moderate adverse effects were the same in both antibiotic and immunoregulators groups in comparison to the placebo but incidence of severe adverse effects in immunoregulator groups was higher than that of antibiotics.

Fibrin glue injection method with diluted thrombin for refractory postoperative digestive fistula.

BACKGROUND: The injection of the biological adhesive fibrin glue is often performed to treat postoperative digestive fistulas. However, it is not always effective especially in case of complex fistulas with large cavities, because the fibrin glue will coagulate before the mixed solutions fill the cavity, creating dead space. We report the results of fibrin glue injection with diluted thrombin solution. METHODS: We studied the tensile strength and coagulation time of the resulting fibrin glue at each dilution of the thrombin solution. Based on in vitro study, 18 patients who had developed postoperative digestive fistula were treated by fibrin glue injection with diluted thrombin solution. RESULTS: In vitro study proved that the dilution of thrombin prolonged the coagulation time of the fibrin glue to more than 1 minute with almost no change to the tensile strength of the glue until a certain dilution was reached. The fistulas of 16 patients were successfully closed. CONCLUSIONS: Our simple method of fibrin glue injection is useful for refractory postoperative digestive fistula, even in cases of complex fistula with large cavities.

Extracorporeal photopheresis for the treatment of refractory Crohn's disease: results of an open-label pilot study.

BACKGROUND: Extracorporeal photopheresis (ECP) is effective in immune-mediated disorders. A prospective, uncontrolled pilot study was conducted to evaluate the safety and efficacy of ECP in patients with active Crohn's disease (CD) who were refractory to or intolerant of immunosuppressants and/or anti-TNF therapies. METHODS: Patients with moderate-to-severely active CD (Crohn's Disease Activity Index [CDAI] 220-450 points) underwent 12 weeks of ECP treatment (Weeks 1-4: twice weekly, every week; Weeks 5-12: twice weekly, every other week). Clinical response was defined as a decrease in the CDAI of >or=100 points or remission (CDAI <150 points) at Week 12. Patients who responded at Week 12 could receive an additional 12 weeks of ECP treatment (twice weekly, every other week) in an extension study. RESULTS: Twenty-eight patients were enrolled with a mean baseline CDAI score of 314 (range 207-457). At Week 12, 14 patients (50%) responded; 13 patients responded within 6 weeks. Seven patients (25%) attained remission by Week 12. Three of 5 patients with open fistulae at baseline had fistula closure. Response was similar among patients naïve to anti-TNF agents and patients who had previously been refractory or intolerant to anti-TNF agents. Of the 12 patients who entered the extension study, 9 (75%) maintained their response at Week 24. CONCLUSIONS: In patients with moderate-to-severely active CD who were refractory to or intolerant of immunosuppressants and/or anti-TNF agents, ECP was well tolerated and induced clinical response (50%) and remission (25%) in patients. Most patients were able to maintain a response with continued treatments.

Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

BACKGROUND & AIMS: This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). METHODS: Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. RESULTS: The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). CONCLUSIONS: Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.

Tacrolimus for Crohn's disease.

(1) Tacrolimus (FK-506) is an immunosuppressant that is being investigated for use in patients with Crohn's disease, mainly in those with refractory illness and fistulizing patterns of the disease. (2) Evidence from a small, randomized controlled trial indicates that, compared with placebo, tacrolimus is associated with higher rates of improvement and similar rates of remission in those with fistulizing patterns of disease. (3) Nephrotoxicity, which has been reported with the use of tacrolimus in clinical trials, seems to improve with dose reduction, but may be associated with irreversible histologic changes. (4) More studies are needed to determine the optimal dose and duration of therapy, and whether the drug is beneficial to patients with non-fistulizing patterns of Crohn's disease.

Fistula-in-ano: do antibiotics make a difference?

BACKGROUND: The objective of this study was to evaluate the hypothesis that antibiotics in conjunction with drainage of anorectal abscesses will reduce the incidence of fistulae formation. The impact of age and associated comorbidity on the formation of fistulae were also evaluated. METHODS: Patients with a diagnosis of anorectal abscesses were identified from the database of a single colorectal practice. Demographic data, comorbidity, antibiotic usage, and fistulae formation were collected from review of patient's charts and phone contact. Statistical analysis was performed with the two-sided Fisher's exact and Wald's chi-square tests. RESULTS: Fifty-six patients with complete data were analyzed. The overall fistulae formation rate was 32%. Of all patients, 45% received a course of broad-spectrum antibiotics at the time of drainage and 48% of patients had associated comorbidity. Although trends were evident, there were no statistical significant associations between fistulae formation and age, comorbidity, and antibiotics. CONCLUSION: Although not statistically significant, there was a trend that antibiotics and age >45 years may be protective against the formation of fistulae. Similarly, the data suggest that the presence of comorbidity may increase the risk of fistula formation. We are encouraged by this result and propose to conduct a larger randomized prospective study.

Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease: a pilot study.

AIMS: To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohn's disease (FCD), which is refractory to conventional therapy including infliximab. METHODS: Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6-mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open-label study of long-term treatment with oral tacrolimus (0.05 mg/kg every 12 h). The evaluation of the clinical response was complemented by use of the perianal Crohn's disease activity index (PCDAI) and magnetic resonance imaging-based score (MRS) with determined periodicity. RESULTS: Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow-up. Five patients were steroid-dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid-dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare-up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months. CONCLUSIONS: Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs.

[Somatostatin in the treatment of pancreatic diseases]. / Somatostatin a hasnyálmirigy betegségeinek kezelésében.

Somatostatin and its synthetic analogues have important physiological roles in human. These compounds antagonize the endocrine and exocrine secretion of pancreas, which provide theoretical ground for their use in patients with pancreatic diseases. For a quarter of a century many researchers have investigated the effect of somatostatin and octreotide in animal models of experimental pancreatitis and in patients with acute pancreatitis, and in those with complications of pancreatic operations, fistulas and pseudocysts. In most of these studies the use of synthetic octreotide with longer duration proved to be more efficient. In experimental and acute pancreatitis somatostatin and octreotide were less effective than expected, however, they proved to be helpful in preventing complications of pancreatic operations and in the therapy of fistulas and pseudocysts.