Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial.

BACKGROUND: The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment. PATIENTS AND METHODS: Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications. RESULTS: Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur. CONCLUSION: Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.

Prevalence of and Risk Factors for Abdominal Bleeding in Patients with External Duodenal Fistula.

BACKGROUND Abdominal bleeding is a severe complication of duodenal fistula, but few studies have focused on this problem. The purpose of the present study was to investigate the prevalence of and risk factors for intra-abdominal bleeding in patients with external duodenal fistula. MATERIAL AND METHODS From January 2014 to December 2016, medical records of 97 patients with external duodenal fistula were retrospectively reviewed and analyzed. The prevalence and risk factors for intra-abdominal bleeding were evaluated. RESULTS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9% (95%CI: 22.5-41.4%). A total of 31 patients had intra-abdominal bleeding. Results revealed that acute kidney failure (OR: 8.462, 95% CI: 1.921-37.28, p=0.005) and retroperitoneal infection (OR: 5.373, 95% CI: 1.504-19.197, p=0.010) were associated with abdominal bleeding. CONCLUSIONS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9%, and acute kidney failure and retroperitoneal infection were found to be risk factors for intra-abdominal bleeding.

Nutrition Management of Home Parenteral Nutrition Among Patients With Enterocutaneous Fistula in the Sustain Registry.

BACKGROUND: Home parenteral nutrition (HPN) is a vital therapy for patients who have the diagnosis of enterocutaneous fistula (ECF), yet little is known about how these patients are managed. This research compares nutrition management of adults with ECF as the indication for HPN therapy to those with other indications. METHODS: This is an analysis of data from adult HPN patients in the Sustain registry enrolled between August 2011 and February 2014 who have the diagnosis of ECF or other indication for HPN who served as the control group. Differences between the ECF and control group were assessed by t test, analysis of variance, or χ2 as appropriate. RESULTS: There were 141 HPN patients with ECF and 632 control patients. Patients with ECF were older (55 vs 50 years, P < .001), more frequently had a goal for future surgery (30% vs 15%, P = .010), had greater prevalence of overweight/obesity (33% vs 20%, P = .04), and had a lower serum albumin (2.98 ± 0.65 g/dL vs 3.16 ± 0.66 g/dL, P = .006) than controls. The diet order was more frequently nil per os (NPO) in patients with ECF (48% vs 22%, P < .001), and amino acid content of HPN was greater (111.90 ± 29.11 vs 102.06 ± 27.84, P < .001) than in controls. There were no differences in patterns of weight change by ECF or control groups, although underweight patients gained, normal-weight patients maintained, and overweight/obese patients lost weight and serum albumin increased similarly. CONCLUSIONS: The HPN management of patients with ECF is similar to other HPN patients other than greater provision of protein, more frequent NPO status, and a goal for future surgery.

Predictive value of preoperative serum C-reactive protein for recurrence after definitive surgical repair of enterocutaneous fistula.

BACKGROUND: Recurrence rates after surgical repair of enterocutaneous fistula (ECF) have not changed substantially. Serum C-reactive protein (s-CRP) has been used as an indicator of postoperative complications in abdominal surgery. ​ The aim of this study was to determine the predictive value of preoperative s-CRP for recurrence after definitive surgical repair of ECF. METHODS: Fifty consecutive patients with ECF persistence submitted electively to definitive surgical repair (ECF resection with primary anastomosis) were included. Among several variables, preoperative s-CRP (primary independent variable) was assessed as a factor related to recurrence (dependent variable). Univariate and multivariate analyses were performed. RESULTS: ECF recurred in 19 patients (38%). Univariate and multivariate analyses disclosed operative blood loss greater than 325 mL (P < .05) and preoperative s-CRP greater than .5 mg/dL (P < .01) as the only risk factors for recurrence. ECF recurrence rates were significantly higher for patients with preoperative s-CRP above this level (53% vs 11%, P < .01). After conservative and surgical management, overall ECF closure was attained in 40 patients (80%). CONCLUSIONS: Our results suggest that s-CRP may serve as a useful parameter to predict potential failure (recurrence) in patients submitted to definitive closure of ECF.

Prognostic value of presepsin for outcomes and complications in enterocutaneous fistula complicated by abdominal sepsis.

BACKGROUND: Enterocutaneous fistula (ECF) poses a supreme challenge for the surgeons associated with abdominal sepsis, fluid electrolyte imbalance and undernutrition. Individual prognostic stratification is pivotal in the clinical management. Presepsin is a novel biomarker showing diagnostic and prognostic value in sepsis. We aimed to evaluate the prognostic value of presepsin in ECF. METHODS: Consecutive patients with ECF were enrolled if diagnosed as abdominal sepsis from June 2014 to June 2015. Serum concentration of presepsin at admission was measured, and medical records including demographics, medical history, treatment modalities, complications and outcomes were collected. Kaplan-Meier curves was drawn to demonstrate the cumulative incidence of source control of infection and fistula closure, and Cox regression analysis was performed to identify independent factors. Association between presepsin and other markers was evaluated by Pearson's correlation coefficient. RESULTS: 71 patients were included with the median presepsin concentration of 726 pg/mL at admission. Baseline presepsin levels showed predictive potential in successful source control of intra-abdominal infection but not in fistula closure. Patients with higher presepsin had more severe intra-abdominal infection as denoted by higher levels of WBC, CRP and PCT, as well as high risks of complications and failure of fistula closure compared with those having lower presepsin (≤726 pg/mL). Presepsin concentration was positively associated with APACHE II score, CRP and PCT. CONCLUSIONS: Presepsin shows prognostic values for source control of abdominal sepsis and clinical courses of ECF. This index may help stratify patients, facilitating the monitoring and adjustment of the therapeutic regimen at an early stage.

Plasma histamine and tumour necrosis factor-alpha levels in Crohn's disease and ulcerative colitis at various stages of disease.

Mast cells secrete numerous mediators and this study investigated plasma levels of histamine, and tumor necrosis factor alpha (TNF-α) in chronic inflammatory bowel disease (IBD). Plasma levels of histamine were determined in 68 patients with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 13 controls. TNF-α levels were assessed in 29 CD patients, 11 UC patients, and in 11 controls. Plasma histamine levels in the control group were 0.25 ng (0.14 - 0.33) and showed no difference to CD (0.19 ng, 0.09 - 0.35) or UC (0.23 ng, 0.11 - 0.60). Significantly lower histamine levels were only found in CD patients on 5-aminosalicylic acid treatment (P ≤ 0.04). Plasma TNF-α levels in the control group were significantly lower 0.44 ml/m(2) (0 - 1.15) than in CD patients (4.62 ml/m(2), 1.82 - 9.22, P = 0.005) or UC (3.14 ml/m(2); 0.08 - 11.34, P = 0.01). In CD disease activity, fistula, and extraintestinal manifestations (EM) were associated with significantly higher plasma TNF-α values, but not the type of treatment. We concluded that in contrast to TNF-α, histamine levels were normal in CD and UC. There is no correlation with histamine and thus the proportion of TNF-α secreted from mast cells in the plasma in patients with IBD is less important.

Serum Sodium: A Reliable and Validated Predictor for Mortality in Enteric Fistula Patients Complicated with Sepsis.

PURPOSE: The aim was to evaluate the predictive value of serial serum sodium determination for mortality in enteric fistula (EF) patients complicated with sepsis. METHODS: Between January 1(st), 2012 to January 13(th), 2013, we performed a prospective observational study enrolling 162 patients. Patients were divided into survivors group (n = 119) and nonsurvivors group (n = 43) according to 28-day outcomes. Laboratory variables on day 0, day 3, and day 7 after admission were recorded. [Na(+)]0 was defined as serum [Na(+)] value on admission. [Na(+)]3 was defined as serum [Na(+)] value on day 3. Δ [Na(+)]3 was defined as changes from [Na(+)]3 to [Na(+)]0. The definition applied to other parameters. The results were validated in an independent cohort of 116 patients. RESULTS: ROC analysis showed that [Na(+)]7>147.5 mmol/L and ΔNa7>5.2 mmol/L were reliable predictors ([Na(+)]7: 81.2% sensitivity, 87.7% specificity, (area under the curve(AUC):0.872, p < .001; Δ[Na(+)]7: 81.3% sensitivity, 83.6% specificity, AUC:0.836, p < .001) for mortality. The combination form ([Na(+)]7>147.5 mmol/L+ Δ[Na]7>5.2 mmol/L+ ΔPCT7<5.3 ng/ml) had greatest predictive value (AUC:0.899, p < .001). Their predictive values were confirmed in the validation cohort. CONCLUSIONS: Serum sodium was a reliable predictor for mortality in abdominal septic patients, which should be paid close attention in the critical care.

[Colovesical fistula as a complication of diverticular disease].

The results of research on the clinical picture, features of manifestation, diagnosis, and treatment of patients with diverticular disease complicated by sigmovesical fistula are presented. The study included 31 patients (19 [61.3%] men, 12 [38.7%] women), aged 32-83 (55.6 +/- 7.1) years. Diagnostic program included physical examination, laboratory blood and urine tests, endoscopic, radiological, ultrasound examinations. All patients underwent different interventions according to the severity and extent of the inflammatory process, the involvement of other organs of the abdominal cavity and the extent of diverticular lesions of the colon. Long-term results were assessed in all patients in a period of 5 months to 12 years, with a median follow-up 4.7 years. It is shown that the clinical manifestations of intestinovesical fistula did not match the severity of complications, and were subclinical. Timing for referral the patient to coloproctologist was 5 months after the occurrence of first clinical signs. In any case, conservative treatment has not led to spontaneous colovesical fistula closure. Average size of parafistulous infiltration on the wall of the bladder and perivesical tissue was 6.5 +/- 2.4 cm. All the patients underwent different types of colon resection. Postoperative complications did not requiring recurrent surgery were detected in 5 (16.1%) patients. None of these has experienced recurrence complications of diverticular disease. For the optimization the treatment strategy, physicians should follow multidisciplinary approach immediately after revealing the patient with persistent bacteriuria, pneumaturia and fecaluria. The surgery is the method of choice in the treatment of colovesical fistula as a complication of diverticular disease.

An aortoduodenal fistula as a complication of immunoglobulin G4-related disease.

Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm, which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level. A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula. The patient received antibiotics and other supportive therapy, and the postoperative course was uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein were noted, which normalized after the introduction of steroid therapy. Control computed tomography angiography showed no endoleaks. The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair.

The C-reactive protein-to-prealbumin ratio predicts fistula closure.

BACKGROUND: The purpose of this study was to evaluate the predictability of fistula closure using the ratio of C-reactive protein to prealbumin (C:P ratio). METHODS: A database of 89 patients with gastrointestinal fistulas (1994-2009) was created based on the records of our Nutrition Support Services Team. All patients had weekly blood work including C-reactive protein level, prealbumin level, and albumin level. Forty-three fistulas were managed without surgery for 6 weeks or more; of these, 29 closed. RESULTS: The median C:P ratio for those fistulas that remained open after 6 weeks of conservative management differed significantly from those that closed (.10 vs .35; P < .001). For patients with a C:P ratio of .25 or less, fistula closure occurred in 87.0% (95% confidence interval, 74.0-94.3), whereas for patients with a ratio of greater than 1.0, no fistulas closed. CONCLUSION: Our results suggest that the C:P ratio is a predictor of fistula closure.

Development of hypertriglyceridemia in patients with enterocutaneous fistulas.

BACKGROUND & AIMS: Hypertriglyceridemia is commonly observed in patients with enterocutaneous fistulas, compromising their health status. In this study potential causes for hypertriglyceridemia in patients with an enterocutaneous fistula are explored and treatment options discussed accordingly. METHODS: A database was created consisting of all consecutively treated patients with an enterocutaneous fistula from 1991 until 2007. Two successive measures of serum triglyceride concentrations of more than 3.0 mmol/L (266 mg/dL) were regarded as hypertriglyceridemia. The relation between fistula specific characteristics and hypertriglyceridemia was analyzed using a multivariable Cox proportional hazard model with time-dependent covariates. RESULTS: A total 102 patients were eligible for this study of whom 25 had hypertriglyceridemia. Multivariable analysis showed that sepsis (HR 4.503, CI 1.778-11.401, P=0.002), high output small bowel fistula (HR 3.534, CI 1.260-9.916, P=0.016), parenteral nutrition (HR 5.689, CI 1.234-26.216, P=0.026) and inflammatory diseases (inflammatory bowel disease vs. malignancy HR 6.211, CI 1.081-35.696, P=0.041) were independent predictors of hypertriglyceridemia. CONCLUSIONS: High triglyceride concentrations in patients with an enterocutaneous fistula were mainly associated with sepsis, a high output small bowel fistula, nutrition by the parenteral route and primary diseases with inflammatory aetiology. This should direct a treatment strategy that focuses on these aspects.

Addition of somatostatin-14 to a standard total parenteral nutrition-mixture in the treatment of fistulae: a clinical, double-blind, randomised, cross-over study.

UNLABELLED: BACKGROUND/STUDY AIMS: Somatostatin and total parenteral nutrition (TPN) are routinely used in the treatment of pancreatic and enterocutaneous fistulae. The objective of this clinical randomised cross-over study was to investigate the serum levels of somatostatin infused alongside TPN by a separate intravenous line, and when it had been added to the TPN mixture. PATIENTS/METHODS: The subjects were recruited by the treating physicians and the nutrition nurses. From the patients who started the study, no one dropped out. Ten patients were treated with a standard TPN mixture and somatostatin 6 mg/day. Patients were randomised to two possible regimens: 'somatostatin plus TPN--somatostatin separately--somatostatin plus TPN' or 'somatostatin separately--somatostatin plus TPN--somatostatin separately'. Each regimen consisted of 3 x 3 days of therapy, during which, serum levels of somatostatin were measured daily. Pre- and posttreatment samples were also analysed. RESULTS: When somatostatin was infused separately, the mean serum level was 884.8 pg/ml (SD: 557.3; range: 54-1900). When added to TPN, the mean serum level was 807.5 pg/ml (SD: 505.8; range 162-2279) (p value of difference = 0,473). The mean pretreatment level was 17.1 pg/ml (SD: 7.5; range: 8-33), and posttreatment was 32.8 pg/ml (SD: 26.5; range: 16-97). CONCLUSIONS: These results demonstrate that serum levels of somatostatin are similar in both treatment regimens and therefore may be added to a TPN mixture.

[Interest of serologic markers in inflammatory bowel disease. About 105 cases]. / Interet du dosage des marqueurs serologiques au cours des maladies inflammatoires cryptogenetiques de l'intestin. A propos d'une serie de 105 malades.

BACKGROUND: The serum markers ASCA and pANCA can help the clinician in certain difficult situations of colites in IBD. The aim of this study was to determine the sensitivity and the specificity of each one of these markers and to establish the characteristics of the positive patients for each one. METHODS: We included patients having a Crohn's disease (CD) or an ulcerative colitis (UC). These patients was compared to a control group. RESULTS: 80 CD patients with an average age of 35.62 years, 25 UC cases with an average age of 34.92 years and 79 healthy subjects with an average age of 34.2 years were included. The ASCA were detected in 33.8% of CD cases , 8% of UC cases of RCH and 2.5% of contro group (p < 000.1). The pANCA were detected in 48% of UC cases, 27.5% of CD patients and 1.3% of controls (p < 000.1). The sensitivity and the specificity of the ASCA and the pANCA for the diagnosis respectively of CD and UC were 33.8%, 97.5% and of 48%, 97.8%. During the CD, the positivity of the ASCA was significantly associated with ileal location (p = 0.001), with the sténosant and/or fistulisant phenotyp of the disease (p = 0.006), the young age at the time of the diagnosis of the CD (p = 0.067) and at a greater frequency of surgical treatment (p = 00.7). The pANCA were more frequently found in colic location of CD (p = 0.09). During UC, the positivity of the pANCA was not associated with the sex, age, loca tion of the disease, medical treatment nor chiurgical treatment. CONCLUSION: The ASCA and pANCA are useful during some clinical situations such as differentiation between IBD otherss colitis and to distinguish CD from UC.

Metabonomics study of intestinal fistulas based on ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC/Q-TOF MS).

Ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC/Q-TOF MS) is an effective and sensitive analytical tool. A UPLC/Q-TOF MS-based metabonomics technique was employed to investigate sera from 40 patients with intestinal fistula and 17 healthy volunteers in an effort to find potential biomarkers of the disease and reveal their pathophysiological changes. After the UPLC/Q-TOF analysis, the retention time and m/z data pair for each peak were detected. Partial least squares discriminant analysis (PLS-DA) and coefficient of correlation analysis were used for marker selection and identification. According to the data, nine potential biomarkers were identified: glycochenodeoxycholic acid, glycocholic [corrected] acid, taurochenodexycholic acid, taurodeoxycholic acid, and two kinds of lysophosphatidyl choline (C16:0 and C18:2) were found with increased concentrations in the patients, and phenylalanine, tryptophan, and carnitine were found with decreased concentrations in the patients. The results suggested that a subclinical hepatic injury and abnormal metabolism of two essential amino acids (phenylalanine and tryptophan), and a key compound of fatty acid synthesis and beta-oxidation (carnitine), occurred in the fistula patients. This work demonstrates the utility of metabonomics as a top-down systems biology tool for understanding clinical problems.

Basic fibroblast growth factor as a response parameter to infliximab in fistulizing Crohn's disease.

BACKGROUND: Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti-tumour necrosis factor-alpha antibody infliximab treatment. AIM AND METHODS: Serum samples, biopsies and patient data from a subgroup of patients included in two placebo-controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4. RESULTS: Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3-10.6 pg/mL). At the end of follow-up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow-up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index > or = 220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3 pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment. CONCLUSIONS: Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.

Mirizzi syndrome with cholecysto-choledocal fistula with a high CA19-9 level mimicking biliary malignancies: a case report.

Mirizzi syndrome type II is a form of obstructive jaundice caused by a stone impacted in the gallbladder neck or the cystic duct that impinges on the common hepatic duct with a cholecysto-choledochal fistula. Preoperative recognition is necessary to prevent injury to the common duct during surgery. We present a patient with an operative diagnosis of type II Mirizzi syndrome, which was not originally indicated in the preoperative work-up; in particular endoscopic retrograde cholangiopancreatography showed stenosis of the middle third of the hepatic duct along with markedly elevated serum CA19-9 levels (up to 35,000 U/mL). Surgical specimen examination did not reveal the presence of neoplasia. We performed cholecystectomy and a jejunal loop was brought up and anastomosed to the common duct at the hilar level in a Roux-en-Y fashion. In cases such as ours with extensive fibrosis and inflamed tissue mimicking cholangiocarcinoma or gallbladder carcinoma, a wide hepaticojejunostomy is required to establish adequate biliary drainage.