S. O. Breukink

Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment for Rectal Cancer

BACKGROUND The aim of this study was to establish the oncological and functional results of organ preservation with a watch-and-wait approach (W&W) and selective transanal endoscopic microsurgery (TEM) in patients with a clinical complete or near-complete response (cCR) after neoadjuvant chemoradiation for rectal cancer. METHODS Between 2004 and 2014, organ preservation was offered if response assessment with digital rectal examination, endoscopy, and MRI showed (near) cCR. Watch-and-wait was offered for cCR, and two options were offered for near cCR: TEM or reassessment after three months. Follow-up included endoscopy and MRIs every three months during the first year, and every six months thereafter. Long-term outcome was assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free survival and Vaizey incontinence score (0 = perfect continence, 24 = totally incontinent). RESULTS One hundred patients were included, with median follow-up of 41.1 months. Sixty-one had cCR at initial response assessment. Thirty-nine had near cCR, of whom 24 developed cCR at the second assessment and 15 patients underwent TEM (9 ypT0, 1 ypT1, 5 ypT2). Fifteen patients developed a local regrowth (12 luminal, 3 nodal), all salvageable and within 25 months. Five patients developed metastases, and five patients died. Three-year overall survival was 96.6% (95% confidence interval [CI] = 89.9% to 98.9%), distant metastasis-free survival was 96.8% (95% CI = 90.4% to 99.0%), local regrowth-free survival was 84.6% (95% CI = 75.8% to 90.5%), and disease-free survival was 80.6% (95% CI = 70.9% to 87.4%). Colostomy-free survival was 94.8% (95% CI = 88.0% to 97.8%), with a good continence after watch-and-wait (Vaizey = 3.4, SD = 3.9) and moderate after TEM (Vaizey = 9.7, SD = 5.1). CONCLUSIONS Organ preservation appears oncologically safe for selected rectal cancer patients with a cCR or near cCR after neoadjuvant chemoradiation when applying strict selection criteria and frequent follow-up, including endoscopy and MRI. The low colostomy rate and the good long-term functional outcome warrant discussing this option with the patient as an alternative to major surgery.

Systematic review and meta-analysis of surgical interventions for high cryptoglandular perianal fistula.

PurposePerianal fistulas, and specifically high perianal fistulas, remain a surgical treatment challenge. Many techniques have, and still are, being developed to improve outcome after surgery. A systematic review and meta-analysis was performed for surgical treatments for high cryptoglandular perianal fistulas.MethodsMedline (Pubmed, Ovid), Embase and The Cochrane Library databases were searched for relevant randomized controlled trials on surgical treatments for high cryptoglandular perianal fistulas. Two independent reviewers selected articles for inclusion based on title, abstract and outcomes described. The main outcome measurement was the recurrence/healing rate. Secondary outcomes were continence status, quality of life and complications.ResultsThe number of randomized trials available was low. Fourteen studies could be included in the review. A meta-analysis could only be performed for the mucosa advancement flap versus the fistula plug, and did not show a result in favour of either technique in recurrence or complication rate. The mucosa advancement flap was the most investigated technique, but did not show an advantage over any other technique. Other techniques identified in randomized studies were seton treatment, medicated seton treatment, fibrin glue, autologous stem cells, island flap anoplasty, rectal wall advancement flap, ligation of intersphincteric fistula tract, sphincter reconstruction, sphincter-preserving seton and techniques combined with antibiotics. None of these techniques seem superior to each other.ConclusionsThe best surgical treatment for high cryptoglandular perianal fistulas could not be identified. More randomized controlled trials are needed to find the best treatment. The mucosa advancement flap is the most investigated technique available.

Disease Outcome of Ulcerative Colitis in an Era of Changing Treatment Strategies: Results from the Dutch Population-based IBDSL Cohort

BACKGROUND AND AIMS In the past decades, treatment options and strategies for ulcerative colitis [UC] have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the past two decades in the South-Limburg area of The Netherlands. METHODS In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 [cohort A], cohort 1998-2005 [cohort B], and cohort 2006-2010 [cohort C]. The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios [HR] for early colectomy [within 6 months after diagnosis], late colectomy [beyond 6 months after diagnosis], and hospitalisation were calculated using Cox regression models. RESULTS In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators [8.1%, 22.8% and 21.7%, respectively, p < 0.01] and biological agents [0%, 4.3% and 10.6%, respectively, p < 0.01] was observed. The early colectomy rate decreased from 1.5% in cohort A to 0.5% in cohort B [HR 0.14; 95% confidence interval 0.04-0.47], with no further decrease in cohort C [0.3%, HR 0.98; 95% confidence interval 0.20-4.85]. Late colectomy rate remained unchanged over time [4.0% vs 5.2% vs 3.6%, respectively, p = 0.54]. Hospitalisation rate was also similar among cohorts [22.3% vs 19.5% vs 18.3%, respectively, p = 0.10]. CONCLUSION Over the past two decades, a reduction in early colectomy rate was observed, with no further reduction in the most recent era. Late colectomy rate and hospitalisation rate remained unchanged over time.

The Disappointing Quality of Published Studies on Operative Techniques for Rectovaginal Fistulas: a Blueprint for a Prospective Multi-institutional Study

BACKGROUND: Treatment of rectovaginal fistulas is difficult, and many surgical interventions have been developed. The best surgical intervention for the closure of these fistulas is still unclear. OBJECTIVE: A systematic review was performed reporting the outcomes of different surgical techniques for rectovaginal fistulas. DATA SOURCES: Medline (PubMed, Ovid), Embase (Ovid), and The Cochrane Library databases were searched for eligible articles as well as the references of these articles. STUDY SELECTION: Two independent reviewers analyzed the search results for eligible articles based on title, abstract, and described results. INTERVENTION(S): Any surgical intervention for the closure of rectovaginal fistulas was included. MAIN OUTCOME MEASURES: The main outcome was closure rate. Secondary outcomes were quality of life, morbidity, and the effect on sexual functioning. RESULTS: Many articles with different operative techniques were identified and classified in the following categories: advancement flaps (endorectal and endovaginal), transperineal closure, Martius procedure, gracilis muscle transposition, rectal resections, transabdominal closure, mesh repair, plugs, endoscopic repairs, closure with biomaterials, and miscellaneous techniques. Results vary widely with closure rates between 0% and >80%. None of the studies were randomized. Because of the poor quality of the identified studies, the comparison of results and performance of a meta-analysis were not possible. Data regarding the secondary outcomes were mostly unavailable. LIMITATIONS: The major limitation of this review was the limited availability of high-quality prospective studies, making it impossible to perform a meta-analysis. CONCLUSIONS: No conclusion about the best surgical intervention for rectovaginal fistulas could be formulated. More large studies of high quality are needed to find the best treatment for rectovaginal fistulas. A design for these high-quality studies was formulated.

Physical and Psychological Effects of Treatment on Sexual Functioning in Colorectal Cancer Survivors

INTRODUCTION As a result of advances in surgical techniques and (neo)adjuvant therapy, mortality rates for colorectal cancer (CRC) have declined significantly in the last two decades. In general, CRC survivors report good health-related quality of life in survivorship. However, many survivors, including those who describe their quality of life as good, also report sexual problems that persist long after treatment is completed. AIMS In this article, we review the effects of different treatment modalities for CRC on sexual functioning in men and women. We highlight both the physical and psychological aspects of CRC treatment and discuss the management of common sexual problems in CRC survivors. METHODS The authors reviewed the existing available published articles regarding this topic. RESULTS Our review of the evidence suggests that surgical treatment and (neo)adjuvant therapy for CRC are commonly associated with a wide range of sexual problems. CONCLUSIONS Sexual functioning is an important functional outcome after CRC treatment and is influenced by a myriad of clinical and patient factors, including an individuals physical and psychological well-being after a diagnosis of CRC. As such, the assessment and management of sexual functioning in men and women with CRC should begin prior to the initiation of treatment and continue throughout treatment and survivorship.

Multimodal treatment of perianal fistulas in Crohn’s disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial

BackgroundCurrently there is no guideline for the treatment of patients with Crohn’s disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs.Methods/DesignThis is a multicentre, randomized controlled trial. Patients with Crohn’s disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs.DiscussionThe PISA trial is a multicentre, randomised controlled trial of patients with Crohn’s disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters.Trial registrationNederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).

Technique for laparoscopic autonomic nerve preserving total mesorectal excision

With the introduction of total mesorectal excision (TME) for treatment of rectal cancer, the prognosis of patients with rectal cancer is improved. With this better prognosis, there is a growing awareness about the quality of life of patients after rectal carcinoma. Laparoscopic total mesorectal excision (LTME) for rectal cancer offers several advantages in comparison with open total mesorectal excision (OTME), including greater patient comfort and an earlier return to daily activities while preserving the oncologic radicality of the procedure. Moreover, laparoscopy allows good exposure of the pelvic cavity because of magnification and good illumination. The laparoscope seems to facilitate pelvic dissection including identification and preservation of critical structures such as the autonomic nervous system. The technique for laparoscopic autonomic nerve preserving total mesorectal excision is reported. A three- or four-port technique is used. Vascular ligation, sharp mesorectal dissection and identification and preservation of the autonomic pelvic nerves are described.

Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-wait Policy Versus Standard Resection – A Matched-controlled Study

BACKGROUND: Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome. OBJECTIVE: The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group). DESIGN: This was a matched controlled study. SETTINGS: This study was conducted at multiple centers. PATIENTS: The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years. MAIN OUTCOME MEASURES: Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score). RESULTS: The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function. LIMITATIONS: This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery. CONCLUSIONS: After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. See Video Abstract at http://links.lww.com/DCR/A395.

Fecal incontinence treated by sacral neuromodulation: Long-term follow-up of 325 patients

Background. Long‐term results of large patient cohorts with fecal incontinence treated by sacral neuromodulation are limited. This study shows the long‐term results after a mean follow‐up of 7.1 years in 325 patients with fecal incontinence treated by continuous sacral neuromodulation. Methods. All patients with fecal incontinence and eligible for sacral neuromodulation between 2000 and 2015 were evaluated retrospectively. Primary outcome was a decrease in episodes of fecal incontinence, which was defined as involuntary fecal loss at least once per week and documented by a 3 week bowel habit diary. Quality of life was assessed using the Short‐Form 36 and the Fecal Incontinence Quality of Life Score. Results. In the study, 374 patients were included for sacral neuromodulation screening and 325 patients (32 male, 9.7%) received permanent, continuous sacral neuromodulation. Mean age was 56.5 years (17–82 years) and mean follow‐up was 7.1 years (3.0–183.4 months). In the 325 patients with permanent sacral neuromodulation, fecal incontinence episodes decreased from a mean of 16.1 ± 14.5 to 3.0 ± 3.7 per 3‐week period after sacral neuromodulation (P < .001) according to the bowel habit diary. Sacral neuromodulation was removed due to unsatisfactory results in 81 patients. Quality of life (both Short‐Form 36 and Fecal Incontinence Quality of Life Score) showed no significant difference compared with the Dutch population during follow‐up. Conclusion. Long‐term efficacy of sacral neuromodulation can be maintained in about half (52.7%) of all patients screened with sacral neuromodulation for fecal incontinence after a mean follow‐up of 7.1 years. Importantly, the quality of life of patients with sacral neuromodulation for fecal incontinence did not differ from the general population.

Time trends in the epidemiology and outcome of perianal fistulizing Crohn’s disease in a population-based cohort

Objective Perianal disease is a debilitating condition that frequently occurs in Crohn’s disease (CD) patients. It is currently unknown whether its incidence has changed in the era of frequent immunomodulator use and biological availability. We studied the incidence and outcome of perianal and rectovaginal fistulas over the past two decades in our population-based Inflammatory Bowel Disease South-Limburg cohort. Patients and methods All 1162 CD patients registered in the Inflammatory Bowel Disease South-Limburg registry were included. The cumulative probabilities of developing a perianal and rectovaginal fistula were compared between three eras distinguished by the year of CD diagnosis: 1991–1998, 1999–2005 and 2006–2011. Second, clinical risk factors and the risk of fistula recurrence were determined. Results The cumulative 5-year perianal fistula rate was 14.1% in the 1991–1998 era, 10.4% in the 1999–2005 era and 10.3% in the 2006–2011 era, P=0.70. Colonic disease was associated with an increased risk of developing perianal disease, whereas older age was associated with a decreased risk (both P<0.01). Over time, more patients were exposed to immunomodulators or biologicals before fistula diagnosis (18.5 vs. 32.1 vs. 52.1%, respectively, P=0.02) and started biological therapy thereafter (18.6 vs. 34.1 vs. 54.0%, respectively, P<0.01). The cumulative 5-year perianal fistula recurrence rate was not significantly different between eras (19.5 vs. 25.5 vs. 33.1%, P=0.28). In contrast, the cumulative 5-year rectovaginal rate attenuated from 5.7% (the 1991–2005 era) to 1.7% (the 2006–2011 era), P=0.01. Conclusion Over the past two decades, the risk of developing a perianal fistula was stable, as well as its recurrence rate, underlining the lasting need for improving treatment strategies for this invalidating condition.OBJECTIVE Perianal disease is a debilitating condition that frequently occurs in Crohns disease (CD) patients. It is currently unknown whether its incidence has changed in the era of frequent immunomodulator use and biological availability. We studied the incidence and outcome of perianal and rectovaginal fistulas over the past two decades in our population-based Inflammatory Bowel Disease South-Limburg cohort. PATIENTS AND METHODS All 1162 CD patients registered in the Inflammatory Bowel Disease South-Limburg registry were included. The cumulative probabilities of developing a perianal and rectovaginal fistula were compared between three eras distinguished by the year of CD diagnosis: 1991-1998, 1999-2005 and 2006-2011. Second, clinical risk factors and the risk of fistula recurrence were determined. RESULTS The cumulative 5-year perianal fistula rate was 14.1% in the 1991-1998 era, 10.4% in the 1999-2005 era and 10.3% in the 2006-2011 era, P=0.70. Colonic disease was associated with an increased risk of developing perianal disease, whereas older age was associated with a decreased risk (both P<0.01). Over time, more patients were exposed to immunomodulators or biologicals before fistula diagnosis (18.5 vs. 32.1 vs. 52.1%, respectively, P=0.02) and started biological therapy thereafter (18.6 vs. 34.1 vs. 54.0%, respectively, P<0.01). The cumulative 5-year perianal fistula recurrence rate was not significantly different between eras (19.5 vs. 25.5 vs. 33.1%, P=0.28). In contrast, the cumulative 5-year rectovaginal rate attenuated from 5.7% (the 1991-2005 era) to 1.7% (the 2006-2011 era), P=0.01. CONCLUSION Over the past two decades, the risk of developing a perianal fistula was stable, as well as its recurrence rate, underlining the lasting need for improving treatment strategies for this invalidating condition.