Sacral neuromodulation in children and adolescents with defecation disorders.

BACKGROUND: Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation. METHODS: A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency. KEY RESULTS: Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity. CONCLUSIONS: SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

BACKGROUND: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. METHODS: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. DISCUSSION: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).

Sacral neuromodulation for low anterior resection syndrome: current status-a systematic review and meta-analysis.

INTRODUCTION: It is estimated that approximately 70% of patients with rectal cancer who undergo surgery will suffer from Low Anterior Resection Syndrome (LARS). In the last decades, sacral neuromodulation (SNM) has been widely used in urinary dysfunction and in faecal incontinence refractory to medical treatment. Its application in LARS has been investigated and has shown promising results. The paper's aim is to present a systematic review and meta-analysis of the available literature and evaluate the therapeutic success of SNM in patients with LARS. METHODS: A systematic search was performed in international health-related databases: Cochrane Library, EMBASE, PubMed and SciELO. No restrictions on year of publication or language were applied. Retrieved articles were screened and selected according to set inclusion criteria. Data items were collected and processed for each included article and a meta-analysis was done according to the PRISMA guidelines. The primary outcome was the number of successful definitive SNM implants. Further outcomes included changes in bowel habits, incontinence scores, quality of life scores, anorectal manometry data and complications. RESULTS: A total of 18 studies were included, with 164 patients being submitted to percutaneous nerve evaluation (PNE) with 91% responding successfully. During follow-up of therapeutic SNM some devices were explanted. The final clinical success rate was 77% after permanent implant. Other outcomes, such as the frequency of incontinent episodes, faecal incontinence scores, quality of life scores were overall improved after SNM. The meta-analysis showed a decrease in 10.11 incontinent episodes/week; a decrease of 9.86 points in the Wexner score and an increase in quality of life of 1.56 (pooled estimate). Changes in anorectal manometry were inconsistent. Local infection was the most common post-operative complication, followed by pain, mechanical issues, loss of efficacy and haematoma. DISCUSSION/CONCLUSION: This is the largest systematic review and meta-analysis concerning the use of SNM in LARS patients. The findings support the available evidence that sacral neuromodulation can be effective in the treatment of LARS, with significant improvement in total incontinent episodes and patients´ quality of life.

[Sacral Neuromodulation for Fecal Incontinence and Constipation: Evidence, Programming and Long-term Management]. / Sakralnervmodulation in der Therapie der Stuhlinkontinenz und Obstipation: Evidenz, Programmierung und Langzeitmanagement.

BACKGROUND: Over the last two decades, sacral neuromodulation (SNM) has established its role in the treatment of functional pelvic organ-/pelvic floor disorders. Even though the mode of action is not fully understood, SNM has become the preferred surgical treatment of fecal incontinence. METHODS AND RESULTS: A literature search was carried out on programming sacral neuromodulation and long-term outcomes in treating fecal incontinence and constipation.Sacral neuromodulation was found to be successful in the long term. Over the years, the spectrum of indications has expanded, and now includes patients presenting with anal sphincter lesions. The use of SNM for low anterior resection syndrome (LARS) is currently under clinical investigation. Findings of SNM for constipation are less convincing. In several randomised crossover studies, no success was demonstrated, even though it is possible that subgroups may benefit from the treatment. Currently the application cannot be recommended in general.The pulse generator programming sets the electrode configuration, amplitude, pulse frequency and pulse width. Usually pulse frequency and pulse width follow a default setting (14 Hz, 210 s), while electrode configuration and stimulation amplitude are adjusted individually to the patient need and perception of stimulation.Despite low infection rates and few electrode-/pulse generator dysfunctions, up to 65% of patients require surgical reintervention during long term follow-up - in 50% of cases because of battery depletion, which is an expected event. At least one reprogramming is necessary in about 75% of the patients during the course of the treatment, mostly because of changes in effectiveness, but rarely because of pain. Regular follow-up visits appear to be advisable. CONCLUSION: Sacral neuromodulation can be considered to be a safe and effective long-term therapy of fecal incontinence. To optimise the therapeutic effect, a structured follow-up regime is advisable.

Noninvasive Sacral Neuromodulation in Children and Adolescents: A Case-Control Study of Patients With Chronic Refractory Constipation.

OBJECTIVES: In adult patients with chronic refractory constipation, invasive sacral neuromodulation (SNM) has been applied successfully. There is a need for less invasive solutions while providing comparable therapeutic effects in children and adolescents. We present a prospective, interventional case-control study on the application of noninvasive SNM. MATERIALS AND METHODS: Patients with chronic constipation refractory to conservative treatment were prospectively included in the study from 2018 to 2021 and randomized to either SNM (SNM group: single current stimulation for 24 h/d, frequency 15 Hz, pulse width 210 µs, intensity 1-10 mA) or conventional treatment (controls: full range of pharmacologic and nonpharmacologic options). Treatment was conducted for 12 weeks. Treatment effects were collected with specialized questionnaires and quality-of-life analysis (KINDLR). Outcome variables were defecation frequency, stool consistency, fecal incontinence (FI) episodes, and abdominal pain. RESULTS: Analysis was conducted in 28 patients with SNM and 31 controls (median age 7.0, range 3-16 years). Overall responsiveness to treatment was 86% of the SNM group and 39% of the control group (p < 0.001). All outcome variables were positively influenced by SNM treatment. Defecation frequency improved in 46% of patients with SNM and in 19% of controls (p = 0.026), as did stool consistency in 57% of patients with SNM and in 26% of controls (p = 0.014). Fecal incontinence was significantly reduced in 76% of patients with SNM (n = 16/21 vs 42% of controls [n = 11/26], p = 0.042). Quality of life improved significantly during SNM treatment (71.32 [baseline] vs 85.00 [after 12 weeks], p < 0.001) and confirmed a positive influence of SNM treatment compared with the control group (85.00 [SNM after 12 weeks] vs 79.29 [controls after 12 weeks], p = 0.047). CONCLUSIONS: Outcome of noninvasive SNM treatment in patients with chronic refractory constipation is better than conventional treatment.

Intraoperative robotic-assisted low anterior rectal resection performance assessment using procedure-specific binary metrics and a global rating scale.

BACKGROUND: This study aimed to evaluate the use of binary metric-based (proficiency-based progression; PBP) performance assessments and global evaluative assessment of robotic skills (GEARS) of a robotic-assisted low anterior rectal resection (RA-LAR) procedure. METHOD: A prospective study of video analysis of RA-LAR procedures was carried out using the PBP metrics with binary parameters previously developed, and GEARS. Recordings were collected from five novice surgeons (≤30 RA-LAR previously performed) and seven experienced surgeons (>30 RA-LAR previously performed). Two consultant colorectal surgeons were trained to be assessors in the use of PBP binary parameters to evaluate the procedure phases, surgical steps, errors, and critical errors in male and female patients and GEARS scores. Novice and experienced surgeons were categorized and assessed using PBP metrics and GEARS; mean scores obtained were compared for statistical purpose. Also, the inter-rater reliability (IRR) of these assessment tools was evaluated. RESULTS: Twenty unedited recordings of RA-LAR procedures were blindly assessed. Overall, using PBP metric-based assessment, a subgroup of experienced surgeons made more errors (20 versus 16, P = 0.158) and critical errors (9.2 versus 7.8, P = 0.417) than the novice group, although not significantly. However, during the critical phase of RA-LAR, experienced surgeons made significantly fewer errors than the novice group (95% CI of the difference, Lower = 0.104 - Upper = 5.155, df = 11.9, t = 2.23, p = 0.042), and a similar pattern was observed for critical errors. The PBP metric and GEARS assessment tools distinguished between the objectively assessed performance of experienced and novice colorectal surgeons performing RA-LAR (total error scores with PBP metrics, P = 0.019-0.008; GEARS scores, P = 0.029-0.025). GEARS demonstrated poor IRR (mean IRR 0.49) and weaker discrimination between groups (15-41 per cent difference). PBP binary metrics demonstrated good IRR (mean 0.94) and robust discrimination particularly for total error scores (58-64 per cent). CONCLUSIONS: PBP binary metrics seem to be useful for metric-based training for surgeons learning RA-LAR procedures.

Reprogramming Sacral Neuromodulation for Sub-Optimal Outcomes: Evidence and Recommendations for Clinical Practice.

OBJECTIVES: In some patients treated for urinary or fecal incontinence with sacral neuromodulation (SNM) persistence of symptoms, a reduction in efficacy or adverse effects of stimulation can occur. In such situations, further programming of the SNM device can help resolve problems. Infrequently hardware failure is detected. This article aims to provide practical guidance to solve sub-optimal outcomes (troubleshooting) occurring in the course of SNM therapy. MATERIALS AND METHODS: A systematic literature review was performed. Collective clinical experience from an expert multidisciplinary group was used to form opinion where evidence was lacking. RESULTS: Circumstances in which reprogramming is required are described. Actions to undertake include changes of electrode configuration, stimulation amplitude, pulse frequency, and pulse width. Guidance in case of loss of efficacy and adverse effects of stimulation, developed by a group of European experts, is presented. In addition, various hardware failure scenarios and their management are described. CONCLUSIONS: Reprogramming aims to further improve patient symptoms or ensure a comfortable delivery of the therapy. Initial changes of electrode configuration and adjustment of stimulation parameters can be performed at home to avoid unnecessary hospital visits. A logical and stepwise approach to reprogramming can improve the outcome of therapy and restore patient satisfaction.

A European snapshot of psychosocial characteristics and patients' perspectives of faecal incontinence-do they correlate with current scoring systems?

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.

The science behind programming algorithms for sacral neuromodulation.

AIM: Sacral neuromodulation (SNM) is a widely adopted treatment for overactive bladder, non-obstructive urinary retention and faecal incontinence. In the majority, it provides sustained clinical benefit. However, it is recognized that, even for these patients, stimulation parameters (such as amplitude, electrode configuration, frequency and pulse width) may vary at both initial device programming and at reprogramming, the latter often being required to optimize effectiveness. Although some recommendations exist for SNM programming, the scientific data to support them are understood by few clinicians. METHODS: This is a narrative review of the literature covering some of the science behind stimulating a mixed peripheral nerve and available preclinical data in the field of SNM. It covers electrode configuration, amplitude, frequency, pulse width and cycling considerations. The review is targeted at clinicians with an interest in the field and does not seek to provide exhaustive detail on basic neuroscience. RESULTS AND CONCLUSIONS: Knowledge of the science of neuromodulation provides some guiding principles for programming but these are broad. These principles are not refuted by preclinical data but specific parameters in clinical use are not strongly supported by animal data, even after the limitations of small and large animal models are considered. The review presents a shortlist of programming principles on a theoretical basis but acknowledges that current practice is as much derived from evolved experience as science.

Programming Algorithms for Sacral Neuromodulation: Clinical Practice and Evidence-Recommendations for Day-to-Day Practice.

BACKGROUND: In sacral neuromodulation (SNM), stimulation programming plays a key role to achieve success of the therapy. However to date, little attention has been given to the best ways to set and optimize SNM programming during the test and chronic stimulation phases of the procedure. OBJECTIVE: Standardize and make SNM programming easier and more efficient for the several conditions for which SNM is proposed. METHODS: Systematic literature review and collective clinical experience report. RESULTS: The basic principles of SNM programming are described. It covers choice of electrode configuration, stimulation amplitude, pulse frequency and pulse widths, while use of cycling is also briefly discussed. Step-by-step practical flow charts developed by a group of 13 European experts are presented. CONCLUSIONS: Programming of SNM therapy is not complex. There are few programming settings that seem beneficial or significantly impact patient outcomes. Only four basic electrode configurations could be identified according to four different options to define the cathode. In a majority of patients, the proposed stimulation parameters will allow a satisfactory improvement for long periods of time. A regular follow-up is, however, necessary to assess and eventually optimize results, as well as to reassure patients.

New Technologies and Applications in Sacral Neuromodulation: An Update.

Recently rechargeable devices have been introduced for sacral neuromodulation (SNM) with conditional safety for full-body magnetic resonance imaging (MRI). Currently a recharge-free SNM device represents the standard implant; however, it is only approved for MRI head scans. As further new technologies with broader MRI capabilities are emerging, the advantages as well as disadvantages of both rechargeable versus recharge-free devices will be briefly discussed in this commentary from the perspective of patients, healthcare professionals, and providers.

Introduction of complete mesocolic excision with central vascular ligation as standardized surgical treatment for colon cancer in Greece. Results of a pilot study and bi-institutional cooperation.

INTRODUCTION: Complete mesocolic excision (CME) is generally accepted as state of the art in colon cancer surgery. However, the long-term impact of CME has not been systematically examined. Therefore cohort studies might be a possible way to clarify any differences between conventional resections and CME. Following bilateral cooperation between the Department of Surgery/University Hospital of Erlangen and the 1st Surgical Department of the General Hospital of Nikaia/Piraeus, including teaching activities for introduction of CME, a cohort study was performed, considering surgical quality criteria and clinical outcome. MATERIAL AND METHODS: All patients with colon carcinomas (CME group, n = 31) referred to the 1st Surgical Department of General Hospital, Nikaia/Piraeus, Greece for surgery from January 2012 to December 2013 were prospectively analyzed and compared with patients who underwent conventional surgery for colon cancer between January 2008 and December 2011 (non-CME group, n = 35). Patients' follow-up was at least 48 months. RESULTS: There were significantly better results in terms of lymph node yield (CME group: 29.6 vs. non-CME group: 17.85; p < 0.001) and lymph node ratio (LNR) (CME group: 0.12 vs. non-CME group: 0.24; p < 0.001) and recurrence-free survival in favor of the CME group (CME group: n = 0 vs. non-CME group: n = 5) without any increase in surgical morbidity (CME group: n = 6 vs. non-CME group: n = 11; p = 0.10). CONCLUSIONS: Complete mesocolic excision appears to offer a superior oncological result without any increase of postoperative morbidity and mortality. Furthermore, CME represents a surgical technique which can be established in a surgical department after previous teaching without increasing the postoperative complication rate.

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

[Modern Strategies for the Treatment of Fecal Incontinence]. / Moderne Therapiestrategien bei Stuhlinkontinenz.

BACKGROUND: Fecal incontinence (FI) is often associated with significant suffering for affected patients and reduction of their quality of life. Fecal incontinence has an underestimated prevalence and will gain in importance in the future due to demographic change in Germany. During the last several years, new technologies have been developed and new evidence has been gathered for existing methods. The aim of this work is to highlight current developments and new treatment options for fecal incontinence. METHODS AND RESULTS: A review of recent literature on the treatment of fecal incontinence was conducted. For conservative therapy, the combination of various treatment options has been proven to be particularly effective. For surgical therapy, long term efficacy of sacral nerve stimulation has been confirmed. Sacral nerve stimulation is now considered first line therapy. Sphincteroplasty remains a valid treatment option in patients with FI due to a sphincter gap. Long term efficacy is low. "Bulking agents" are an alternative - predominantly in passive FI, although the evidence is limited due to the use of different substances and techniques, lack of long-term results and suboptimal study designs. For the treatment of FI in the context of a masked defecation disorder, ventral mesh rectopexy has become established. CONCLUSION: The spectrum of therapeutic options for the treatment of FI is continuously evolving. There is consensus that conservative treatment should be the initial therapy. Currently only a limited number of established surgical options are available. Development and evaluation of new treatment options and further improved evidence of efficacy of the existing treatment modalities are desirable.

To what extent is the low anterior resection syndrome (LARS) associated with quality of life as measured using the EORTC C30 and CR38 quality of life questionnaires?

PURPOSE: Treatment of rectal cancer often results in disturbed anorectal function, which can be quantified by the Low Anterior Resection Syndrome (LARS) score. This study investigates the association of impaired anorectal function as measured with the LARS score with quality of life (QoL) as measured with the EORTC-QLQ-C30 and CR38 questionnaires. METHODS: All stoma-free patients who had undergone sphincter-preserving surgery for rectal cancer from 2000 to 2014 in our institution were retrieved from a prospective database. They were contacted by mail and asked to return the questionnaires. QoL was evaluated in relation to LARS and further patient- and treatment factors using univariate and multivariate analysis. RESULTS: Of the eligible patients (n = 331), 261 (78.8%) responded with a complete LARS score. Mean score for global QoL according to the EORTC-QLQ-C30 questionnaire was 63 ± 21 for all patients. If major LARS was present, mean score decreased to 56 ± 19 in contrast to 67 ± 20 in patients with no/minor LARS (p < 0.001). In regression analysis, major LARS was furthermore associated with reduced physical, role, emotional, cognitive and social functioning as well as impaired body image, more micturition problems and poorer future perspective. It was not related to sexual function. The variance explained by major LARS in the differences of QoL was approximately 10%. CONCLUSION: The presence of major LARS after rectal resection for cancer is negatively associated with global health as well as many other aspects of QoL. Preserving anorectal function and treatment of LARS are potential measures to improve QoL in this patient group.

[Initiating a Robotic Program for Abdominal Surgery - Experiences from a Centre in Germany]. / Implementierung eines Roboterprogramms in der Viszeralchirurgie ­ Erfahrungen eines deutschen Zentrums.

PURPOSE: Robotic systems are becoming increasingly important in abdominal surgery. We describe the implementation of a robotic program at a German centre for abdominal surgery, with focus on feasibility, safety, patient selection, learning curves, financial aspects and the lessons learned. METHODS: This retrospective analysis covered data on patient demographics, intra- and postoperative parameters, oncological results and costs of all robotic-assisted abdominal operations performed at our institution between August 2012 to December 2016. It was also evaluated how possible factors for preoperative patient selection might influence intra- or postoperative outcome and learning parameters. RESULTS: 81 operations were performed - mostly colorectal resections (n = 35), ventral mesh rectopexy (n = 23) and liver resections (n = 18). The conversion rate was 7%. All oncological patients underwent R0 resection. Mean postoperative hospitalisation was 8.8 days; mean morbidity was 24%, with major complications (Clavien-Dindo > II) in 7%; mortality was 0%. BMI above 33.5 kg/m2 was associated with significantly higher morbidity (p = 0.024) and rate of major complications (p = 0.046), as well as a significantly longer hospitalisation (p = 0.009). Patients older than 65 years had significantly higher morbidity (p = 0.025). With increasing numbers of operations, time of surgery decreased (p = 0.001). The average cost of a robot-assisted operation, including hospital stay, was 15,221 €. The costs of robotic sigmoid resections or liver resections were higher (compared to the open approach: 106.8 and 62.8% higher, respectively, compared to the laparoscopic approach 93.5 and 66.5% higher, respectively). CONCLUSIONS: Robotic surgery is a safe approach. A crucial factor in the successful and safe performance of robotic assisted operations is proper patient selection, especially during the implementation period. The inevitable learning curve and the higher costs compared to open and laparocopic surgery must be respected and specialisation of the whole team is necessary.

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus.

PURPOSE: To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer. METHODS: Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I-IV anal cancer received chemoradiotherapy with 5­fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4-6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT). RESULTS: Median follow-up was 41 (2-165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3-4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009). CONCLUSION: Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).