[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.

[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.

Weekly high-dose 5-fluorouracil as 24-h infusion and folinic acid (AIO) plus irinotecan as second- and third-line treatment in patients with colorectal cancer pre-treated with AIO plus oxaliplatin.

Our objective was to evaluate the efficacy and safety of high-dose 5-fluorouracil (5-FU) as a 24-h infusion and folinic acid (FA) (AIO regimen) plus irinotecan (CPT-11) after pre-treatment with AIO plus oxaliplatin (L-OHP) in colorectal carcinoma (CRC). Twenty-six patients with non-resectable distant CRC metastases were analyzed for second- or third-line treatment with AIO plus CPT-11 after pre-treatment with AIO plus L-OHP. On an outpatient basis, the patients received a treatment regimen comprising weekly 80 mg/m2 CPT-11 in the form of a 1-h i.v. infusion and 500 mg/m2 FA as a 1- to 2-h i.v. infusion, followed by 2000 mg/m2 5-FU i.v. administered as a 24-h infusion once weekly. A single treatment cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 26 patients received 344 chemotherapy applications with AIO plus CPT-11. The main symptom of toxicity was diarrhea (NCI-CTC toxicity grade 3+4) occurring in five patients (19%; 95% CI 7-39%). Nausea and vomiting presented in two patients (8%; 95% CI 1-25%). The response rate of 26 patients can be summarized as follows: partial remission: n=7 (27%; 95% CI 12-48%); stable disease: n=9 (35%; 95% CI 17-56%) and progressive disease: n=10 (38%; 95% CI 20-59%). The median progression-free survival (n=26) was 5.8 months (range 3-13), the median survival time counted from the treatment start with the AIO plus CPT-11 regimen was 10 months (range 2-24) and counted from the start of first-line treatment (n=26) was 23 months (range 10-66). We conclude that the AIO regimen plus CPT-11 is practicable in an outpatient setting and well tolerated by the patients. Tumor control was achieved in 62% of the patients. The median survival time was 10 months and the median survival time from the start of first-line treatment (n=26) was 23 months.

P27 does not predict histopathological response to radiochemotherapy in rectal cancer.

BACKGROUND: Tumor response to radiochemotherapy (RCT) varies considerably, even among patients treated in accordance with the same protocol. The aim of the present study was to test the predictive value of the cell-cycle inhibitor p27kip1 with regard to neoadjuvant RCT response in rectal cancer. MATERIALS AND METHODS: P27kip1 was evaluated by immunohistochemistry in pretreatment biopsy material obtained from 42 patients with rectal cancer treated uniformly in accordance with an identical prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Four expression patterns (staining intensity [-,+,++,+++] and the percentage of positive cells, evaluated separately for nuclei and cytoplasm) of p27kip1 were investigated for correlation with tumor response, which was assessed in the resected surgical specimen using a histopathological five-point grading system. Additionally, p27(kip1) expression was investigated for correlation with several pathological features, overall survival, and disease-free survival. RESULTS: p27kip1 expression was as follows: nuclear intensity: -: 8, +: 19, ++: 11, +++: 4 cases, median percentage of positive cells: 18.75%; cytoplasmic intensity: -: 0, +: 25, ++: 12, +++: 3 cases, median percentage of positive cells: 70%. Histopathological tumor regression was acceptable in 30 patients (3 complete; 27 good) and inadequate in 12 patients (7 moderate; 5 minimal). No tumor failed to show some regression. No significant correlation was found between any of the p27kip1 expression patterns and RCT response, tumor differentiation (low grade versus high grade), cT- and ypT-category, UICC stage, overall survival, and disease-free survival. CONCLUSIONS: p27kip1 cannot aid the individualization of multimodal treatment strategies in rectal cancer, nor can it serve as a predictor of survival.

Bilateral sacral spinal nerve stimulation for fecal incontinence after low anterior rectum resection.

BACKGROUND AND AIMS: The somatomotor innervation pattern has been shown to differ in patients undergoing percutaneous nerve evaluation for sacral nerve stimulation. In some patients bilateral stimulation might improve clinical outcome; however, only single-channel pulse generators have until now been available. We report a patient with fecal incontinence after surgery for rectal carcinoma in whom a dual-channel, individually programmable, pulse generator permitted implantation of neurostimulation electrodes bilaterally. PATIENTS AND METHODS: Intractable fecal incontinence developed in a 48-year-old man who underwent low anterior rectum resection, owing mainly to reduced internal anal sphincter function. The morphology of the anal sphincter was without defect. Based on the findings of unilateral and bilateral temporary sacral nerve stimulation the patient underwent placement of foramen electrodes on S4 bilaterally. Both electrodes were connected to a dual-channel impulse generator for permanent low-frequency stimulation. RESULTS: The percentage of incontinent bowel movements decreased during unilateral test stimulation from 37% to 11%, during bilateral test stimulation to 4%, and with chronic bilateral stimulation to 0%. The Wexner continence score improved from 17 preoperatively to 2, and quality of life (ASCRS score) was notably enhanced. Anorectal manometry revealed improved striated anal sphincter function; the internal anal sphincter remained unaffected. CONCLUSION: Sacral nerve stimulation can effectively treat incontinence after rectal resection, and bilateral stimulation can improve the therapeutic effect.