Hyperbaric oxygen therapy for the treatment of rectovaginal fistulas in patients with Crohn's disease: results of the HOT-REVA pilot study.

BACKGROUND: Positive effects of hyperbaric oxygen (HBO) on perianal fistulas in Crohn's disease (CD) have been described, but the effect on rectovaginal fistulas (RVFs) has not yet been studied. The aim was to investigate the efficacy, safety and feasibility of HBO in patients with RVF in CD. METHODS: In this prospective study, consecutive CD patients between November 2018 and February 2020 presenting with RVF at the outpatient fistula clinic of the Amsterdam University Medical Centre were included and selected to receive treatment with 30 daily HBO sessions, if fistulas were actively draining and any concomitant treatment regimen was stable at least 6 weeks prior to start of HBO. Patients with a stoma were excluded. The primary endpoint was clinical closure at 3-month follow-up, defined as cessation of complaints and/or closure of the external orifice if visible at baseline. Secondary outcomes were improvement of concomitant perianal fistulas as measured by the perianal disease activity index (PDAI) and fistula drainage assessment (FDA), as well as improvement in patient-reported outcomes (visual analogue scale (VAS), inflammatory bowel disease questionnaire (IBDQ), faecal incontinence quality of life scale (FIQL) and female sexual functioning index (FSFI)) at 3-month follow-up. RESULTS: Out of 14 eligible patients, nine patients (median age 50 years) were treated, all of whom had previously had one or more unsuccessful medical and/or surgical treatments for their RVF. Clinical closure occurred in none of the patients at 3-month follow-up. There was no improvement in PDAI and patient-reported outcomes (VAS, IBDQ, FIQL and FSFI). Two patients had concomitant perianal fistulas; using FDA, one patient had a clinical response and one patient was in clinical remission 3 months after HBO. There were two treatment-related adverse events during HBO concerning claustrophobia and fatigue. Furthermore, two patients had a surgical intervention due to RVF and two patients were treated with antibiotics for a urinary tract infection during follow-up. One patient had a dose reduction of ustekinumab because of decreased luminal complaints. CONCLUSION: Treatment with HBO was feasible, but in this therapy-refractory cohort without deviating ostomy no clinical closure of RVF or improvement in quality of life was seen 3 months after HBO. Treatment with HBO alone in this specific group of patients therefore appears to be ineffective.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in Crohn's disease (HOT-TOPIC): study protocol of a prospective interventional cohort study with one-year follow-up.

Background: Perianal fistulizing Crohn's disease (pCD) has a significant impact on patients' health and quality of life. Current treatment options have a relatively low success rate and a high recurrence risk. Positive effects of hyperbaric oxygen (HBO2) therapy have been indicated in animal studies as well as in small case series. Methods/Design: This is a non-randomized, controlled pilot study. A total of 20 patients with pCD who have been refractory to standard therapy for at least six months will be included. Patients with a seton and stable treatment regimen will be included. Patients with anal strictures, rectovaginal fistulas, stoma or deep ulceration of the rectum will be excluded. Patients who are eligible but refuse HBO2 will be asked to serve as controls. Patients in the HBO2 group will be treated with 40 sessions of HBO2 therapy at 243-253 kPa, with the seton being removed after 30 sessions. Co-primary endpoints are changes in the perianal disease activity index and MRI-scores. Secondary outcomes are fistula drainage assessment, laboratory findings and patient-reported outcomes. Assessment will be done at baseline, 16 weeks, 34 weeks and 60 weeks after finishing HBO2. Discussion: The aim of this study is to investigate the feasibility and therapeutic effect of HBO2 on pCD. The one-year follow-up should provide information on the effect durability. A comparison between patients treated with HBO2 and patients who continue to receive standard care will be made. The risk of bias will be limited by using clearly defined inclusion and exclusion criteria, baseline characteristics and consecutive recruitment of patients through an outpatient fistula clinic. Trial registration: The HOT-TOPIC trial has been approved by the local Medical Ethical Committee of the Academic Medical Centre in Amsterdam, the Netherlands. The trial has been registered at the Netherlands Trial Register (www.trialregister.nl), registration number: NTR 6676. Protocol version: August 2017, version 3.0.

The impact of the national bowel screening program in the Netherlands on detection and treatment of endoscopically unresectable benign polyps.

BACKGROUND: In January 2014, a national bowel cancer screening program started in the Netherlands. The program is being implemented in phases until 2019. Due to this program, an increase in patients referred for a colorectal resection for benign, but endoscopically unresectable polyps, is expected. So far, most resections are performed according to oncological principles despite no pre-operative histological diagnosis of malignancy. The aim of this study was to analyze the increase in referred patients during the first year of the screening program and to compare pathological results and clinical outcome of resections of patients undergoing resection for benign polyps before and after implementation of screening. METHODS: Patients referred for colorectal resection without biopsy-proven cancer between January 2009 and January December 2014 were identified from a prospectively maintained database. Patients with endoscopically macroscopic features of carcinoma were excluded. RESULTS: Seventy-six patients were included. Forty-seven patients (61.8%) were operated on in the 5 years prior to implementation of the screening program, and 29 patients (38.2%) were operated during the first year of implementation of the screening program. The overall malignancy rate before the introduction of the program was 14.1 and 6.6% after it had started (p = .469). All resections were performed laparoscopically; the conversion rate was 3.9% (n = 3). The overall mortality rate was 2.7% (n = 2), major complications (Clavien-Dindo > 3b) occurred in 11.8% (n = 9) of patients. The anastomotic leakage rate was 3.9% (n = 3). CONCLUSIONS: The number of patients referred for benign polyps tripled after introduction of the screening program. With an overall major morbidity and mortality rate of 11.8%, it seems valid to discuss whether an endoscopic excision with advanced techniques with or without laparoscopic assistance would be preferable in this patient group, accepting a 6.6% reoperation rate for additional oncological resection with lymph node sampling in patients in whom a malignancy is found on histological analysis of the complete polyp.

Colorectal anastomotic leak: delay in reintervention after false-negative computed tomography scan is a reason for concern.

BACKGROUND: Early detection of anastomotic leakage (AL) after colorectal surgery followed by timely reintervention is of crucial importance. The aim of this study was to investigate the accuracy of computed tomography (CT) imaging for AL and the effects of delay in reintervention after a false-negative CT. METHODS: All files from patients who had colorectal surgery with primary anastomoses between 2009 and 2014 were reviewed. The predictive value of CT scanning for AL was determined and correlated with short-term postoperative patient outcomes. In addition, factors predictive of false-negative scans were assessed. RESULTS: Six hundred and twenty-eight patient files were reviewed. In total, a CT scan was performed in 127 patients. Overall, leakage was seen in 49 patients (7.8%). The positive and negative predictive values were 78 and 88%, respectively. Sensitivity was 73% and specificity 91%. In patients with a true-positive CT (n = 24), reintervention followed after a median interval of 0 days (IQR 1), whereas this was 1 day (IQR 2) in the false-negative group (n = 11) (p < 0.05). This was associated with a significantly increased mortality rate (1/24 = 4.2% vs 5/11 = 45.5%) (p < 0.005), an increased length of hospital stay [median 28 days (IQR 26) vs 54 days (IQR 20) (p < 0.05)]. CONCLUSIONS: Delayed reintervention after false-negative CT scanning is associated with a high mortality rate and a significant increase in length of hospital stay.

Iron therapy for the treatment of preoperative anaemia in patients with colorectal carcinoma: a systematic review.

AIM: Preoperative anaemia is associated with increased morbidity and mortality. The aim of this systematic review is to evaluate the efficacy of preoperative iron supplementation in the treatment of anaemia, and its effect on the postoperative recovery of patients undergoing surgery for colorectal carcinoma. METHOD: This systematic review was performed using MEDLINE, EMBASE and the Cochrane library to assess current evidence on the role of iron supplementation in the treatment of preoperative anaemia. Our main outcomes were absolute increase in haemoglobin, blood transfusion rate and postoperative morbidity. Main inclusion criteria were: preoperative iron supplementation, presence of colorectal carcinoma and elective surgery. The Downs-Black questionnaire was used for quality assessment of the included studies. RESULTS: Of the 605 studies analysed, seven, three randomized controlled trials and four cohort studies, were included. Despite iron supplementation, the three randomized controlled trials showed a decrease in haemoglobin level. This was contrary to the four cohort studies which all showed a significant increase. All studies showed a decreased blood transfusion rate following iron supplementation. None of the included studies assessed postoperative morbidity. Due to heterogeneity in study design, duration of treatment, dosages and variation in iron substrates, we were unable to perform a meta-analysis. CONCLUSION: In anaemic patients who require surgery for colorectal carcinoma, current evidence is of inadequate quality to draw a definitive conclusion on the efficacy of the various measures to treat preoperative anaemia.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy in a short stay setting in patients with colorectal cancer at high risk of peritoneal carcinomatosis.

INTRODUCTION: Treatment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is relatively ineffective and associated with morbidity. This raises the question whether we should focus on prevention of the development of PC. We determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in a short stay setting. METHODS: A prospective single centre pilot study was conducted between January 2011 and July 2012. Ten patients at risk of developing PC of CRC origin were included. Laparoscopic HIPEC using Mitomycin-C (90 min; inflow temperature 42-43 °C) was performed within several weeks after primary resection of CRC and was considered feasible when postoperative hospital stay was three days or shorter in at least six patients, and if a maximum of one conversion and one re-admission within 30 days occurred. RESULTS: HIPEC was performed after a median of 6 weeks (range 3-9 weeks). Postoperatively, five patients were discharged at day one, four patients at day two and one patient at day three. Laparoscopic adhesiolysis resulted in small bowel injury in one patient, but no conversion to open surgery and no postoperative complications were observed. One patient was readmitted within 30 days due to a clostridium infection. The postoperative course was uneventful for the remaining patients. CONCLUSION: Adjuvant laparoscopic HIPEC appeared to be feasible in a short stay setting based on this small pilot study. The necessity of adhesiolysis determines the complexity of the procedure and requires an operating team with experience in minimally invasive abdominal surgery.