A Dutch prediction tool to assess the risk of incidental gallbladder cancers after cholecystectomies for benign gallstone disease.

BACKGROUND: Despite the increasing implementation of selective histopathologic policies for post-cholecystectomy evaluation of gallbladder specimens in low-incidence countries, the fear of missing incidental gallbladder cancer (GBC) persists. This study aimed to develop a diagnostic prediction model for selecting gallbladders that require additional histopathological examination after cholecystectomy. METHODS: A registration-based retrospective cohort study of nine Dutch hospitals was conducted between January 2004 and December 2014. Data were collected using a secure linkage of three patient databases, and potential clinical predictors of gallbladder cancer were selected. The prediction model was validated internally by using bootstrapping. Its discriminative capacity and accuracy were tested by assessing the area under the receiver operating characteristic curve (AUC), Nagelkerke's pseudo-R2, and Brier score. RESULTS: Using a cohort of 22,025 gallbladders, including 75 GBC cases, a prediction model with the following variables was developed: age, sex, urgency, type of surgery, and indication for surgery. After correction for optimism, Nagelkerke's R2 and Brier score were 0.32 and 88%, respectively, indicating a moderate model fit. The AUC was 90.3% (95% confidence interval, 86.2%-94.4%), indicating good discriminative ability. CONCLUSION: We developed a good clinical prediction model for selecting gallbladder specimens for histopathologic examination after cholecystectomy to rule out GBC.

Fluxomics reveals cellular and molecular basis of increased renal ammoniagenesis.

The kidney plays a critical role in excreting ammonia during metabolic acidosis and liver failure. The mechanisms behind this process have been poorly explored. The present study combines results of in vivo experiments of increased total ammoniagenesis with systems biology modeling, in which eight rats were fed an amino acid-rich diet (HD group) and eight a normal chow diet (AL group). We developed a method based on elementary mode analysis to study changes in amino acid flux occurring across the kidney in increased ammoniagenesis. Elementary modes represent minimal feasible metabolic paths in steady state. The model was used to predict amino acid fluxes in healthy and pre-hyperammonemic conditions, which were compared to experimental fluxes in rats. First, we found that total renal ammoniagenesis increased from 264 ± 68 to 612 ± 87 nmol (100 g body weight)-1 min-1 in the HD group (P = 0.021) and a concomitated upregulation of NKCC2 ammonia and other transporters in the kidney. In the kidney metabolic model, the best predictions were obtained with ammonia transport as an objective. Other objectives resulting in a fair correlation with the measured fluxes (correlation coefficient >0.5) were growth, protein uptake, urea excretion, and lysine and phenylalanine transport. These predictions were improved when specific gene expression data were considered in HD conditions, suggesting a role for the mitochondrial glycine pathway. Further studies are needed to determine if regulation through the mitochondrial glycine pathway and ammonia transporters can be modulated and how to use the kidney as a therapeutic target in hyperammonemia.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study.

OBJECTIVES: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. DESIGN: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. SETTING: Not applicable. PATIENTS: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. CONCLUSIONS: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

Method for adequate macroscopic gallbladder examination after cholecystectomy.

BACKGROUND AND AIMS: There is no clear guideline nor protocol for macroscopic examination of the gallbladder, leaving surgeons extemporaneous in regard of gallbladder examination in selective histopathologic policy. The purpose of this article is to describe a surgical approach for adequate macroscopic inspection of the gallbladder. MATERIALS AND METHODS: The described practical method was developed in collaboration between surgeons and pathologists. This method was introduced in 2011 and implemented in 2012. We retrospectively reviewed the number of cholecystectomies and number of histopathologic examinations between 2006 and 2017, using our own patient database. We used the Netherlands Cancer Registry (NCR) to examine the incidence of gallbladder cancer patients before and after implementation of the selective policy in our hospital. In addition to the method, we depict several frequent macroscopic abnormalities in order to provide some examples for surgical colleagues. RESULTS: Since implementation of the selective policy, 2271 surgical macroscopic gallbladder examinations were performed. As a result, we observed a significant decrease from 83% in 2012 to 38% in 2017, in histopathologic examination of the gallbladder following cholecystectomy. We observed a stable trend of gallbladder carcinoma in the same period (0.17%, n = 4 during 2006-2011 and 0.26%, n = 6 during 2012-2017). CONCLUSION: A simple, valid and easy method is described for future macroscopic analysis by the surgeon following a cholecystectomy.

Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: The aim was to evaluate the various operative techniques and outcomes used to manage the pancreatic transection plane (or stump) during a left (distal) pancreatectomy and to develop expert consensus guidelines. METHODS: Evidence-based, clinically relevant questions were discussed and then were circulated among members of the International Study Group of Pancreatic Surgery. After agreement on the questions and statements, voting in a 9-point Likert scale was used to gauge the level of objective support for each. RESULTS: Studies using the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula including 16 randomized trials were reviewed to generate a series of statements set into 14 domains. There was strong consensus in the following statements: there was no difference in the postoperative pancreatic fistula rate after left pancreatectomy between the handsewn and stapler techniques; a stapling technique could not be used in all cases of left pancreatectomy; the use of an energy-based tissue sealant or a chemical sealant device or combinations of these did not impact the postoperative pancreatic fistula rate; there was no difference in the postoperative pancreatic fistula rate between the open, laparoscopic, or robotic approaches; and there are 1 or more clinically important, patient-related risk factors associated with the postoperative pancreatic fistula rate. There was weak or conditional agreement on the use of prophylactic somatostatin analogs, stents, stump closure, stump anastomosis, and the role of abdominal drains. CONCLUSION: Areas of strong consensus suggests a change in clinical practice and priority setting. Eight domains with lower agreement will require novel approaches and large multicenter studies to determine future key areas of practice.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial.

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Trial Registration: ISRCTN Identifier: ISRCTN45877994.

Paraganglion, a pitfall in diagnosis after regular cholecystectomy.

INTRODUCTION: Neuroendocrine neoplasm of the gallbladder is an extremely uncommon diagnosis. We present a case of a benign gallbladder paraganglion that was initially incorrectly diagnosed as a neuroendocrine tumour (NET). PRESENTATION OF CASE: A 27-year-old female with symptomatic gallstone disease underwent an uncomplicated laparoscopic cholecystectomy. Routine histopathologic examination suggested the presence of a small adventitial NET. However, histopathological revision was performed by our pathologist because of regional gallbladder carcinoma (GBC) treatment evaluation. The revision demonstrated the presence of a normal paraganglion, a preexistent structure that is only rarely encountered during routine histopathologic examination of the gallbladder. DISCUSSION: Neuroendocrine neoplasms of the gallbladder are extremely rare. Treatment varies from a simple cholecystectomy to extensive surgical resections. Chemotherapy is usually reserved for metastatic disease. In contrast, a gallbladder paraganglion is a benign entity not requiring additional treatment. CONCLUSION: A neuroendocrine neoplasm of the gallbladder may closely resemble a benign paraganglion. If a NET is suspected, the clinician should be aware of the histopathologic mimicry of a paraganglion prior to initiating additional treatments.

Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases.

For colorectal liver metastases (CRLM), surgical resection is the only potentially curative therapy, but even successfully resected patients often face disease recurrence, leading to 5-year survival rate below 50%. Despite available preoperative stratification strategies, it is not fully elucidated which patients actually benefit from CRLM resection. Here we evaluated osteopontin, a secreted glyco-phosphoprotein, as a biomarker in the context of CRLM resection. Tissue levels of osteopontin were analysed in CRLM using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Pre- and postoperative osteopontin serum concentrations were analysed by enzyme-linked immunosorbent assay (ELISA) in 125 patients undergoing resection of CRLM as well as 65 healthy controls. Correlating with an upregulation of osteopontin tissue expression in CRLM, osteopontin serum levels were significantly elevated in patients with CRLM compared to healthy controls. Importantly, high pre- and post-operative osteopontin serum levels were associated with a poor prognosis after tumour resection. Patients with initial osteopontin serum levels above our ideal cut-off value of 264.4 ng/mL showed a significantly impaired median overall survival of 304 days compared to 1394 days for patients with low osteopontin levels. Together, our data suggest a role of osteopontin as a prognostic biomarker in patients with resectable CRLM that might help to identify patients who particularly benefit from liver resection.

Colicky pain and related complications after cholecystectomy for mild gallstone pancreatitis.

BACKGROUND: Same-admission cholecystectomy is advised after gallstone pancreatitis to prevent recurrent pancreatitis, colicky pain and other complications, but data on the incidence of symptoms and complications after cholecystectomy are lacking. METHODS: This was a prospective cohort study during the previously published randomized controlled PONCHO trial on timing of cholecystectomy after mild gallstone pancreatitis. Data on healthcare consumption and questionnaires focusing on colicky pain and biliary complications were obtained during 6 months after cholecystectomy. Main outcomes were (i) postoperative colicky pain as reported in questionnaires and (ii) medical treatment for postoperative symptoms and gallstone related complications. RESULTS: Among 262 patients who underwent cholecystectomy after mild gallstone pancreatitis, 28 of 191 patients (14.7%) reported postoperative colicky pain. The majority of these were reported within 2 months after surgery and were single events. Overall, 25 patients (9.5%) required medical treatment for symptoms or gallstone related complications. Acute readmission was required in seven patients (2.7%). No predictors for the development of postoperative colicky pain were identified. DISCUSSION: Some 15% of patients experienced colicky pain after cholecystectomy for mild gallstone pancreatitis, which were mostly single events and rarely required readmission. These data may be used to better inform patients undergoing cholecystectomy for mild gallstone pancreatitis.

Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.

BACKGROUND: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. METHODS: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. DISCUSSION: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. TRIAL REGISTRATION: Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

Elderly Patients Strongly Benefit from Centralization of Pancreatic Cancer Surgery: A Population-Based Study.

BACKGROUND: Series from expert centers suggest that pancreas cancer surgery is safe for elderly patients but nationwide data, taking hospital volume into account, are lacking. METHODS: From the Netherlands Cancer Registry, all 3420 patients who underwent pancreatoduodenectomy (PD) for primary pancreatic or periampullary carcinoma in 2005-2013 were selected. Associations between age (<75, ≥75 years), hospital volume (tertiles), and postoperative mortality (30, 90 day) were evaluated by χ (2) tests and logistic regression analyses. Overall survival was investigated by means of Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: The proportion of elderly patients (≥75 years) undergoing PD increased from 15 % in 2005-2007 to 20 % in 2011-2013 (p = 0.009). In low (<15 per year), medium (15-28 per year), and high (>28 per year) hospital volume tertiles, the proportion of elderly patients was 16, 20, and 17 %, respectively (p = 0.10). With increasing hospital volume, 30-day postoperative mortality was 6.0-4.5-2.9 % (p = 0.002) and 90-day mortality 9.3-8.0-5.3 % (p = 0.001), respectively. Within each volume tertile, adjusted 30- and 90-day mortality of elderly patients was 1.6-2.5 times higher compared to outcomes of younger patients. Adjusted 30-day mortality in elderly patients was higher in low-volume hospitals (odds ratio = 2.87, 95 % confidence interval 1.15-7.17) compared to high-volume hospitals. Similarly, elderly patients had a worse overall survival in low-volume hospitals (hazard ratio = 1.28, 95 % confidence interval 1.01-1.63). Postoperative mortality of elderly patients in high-volume hospitals was similar to mortality of younger patients in low- and medium-volume hospitals. CONCLUSIONS: Elderly patients benefit from centralization by undergoing PD in high-volume hospitals, both with respect to postoperative mortality and survival. It would seem reasonable to place elderly patients into a high-risk category; they should only undergo surgery in the highest-tertile-volume hospitals.

The role of routine fine-needle aspiration in the diagnosis of infected necrotizing pancreatitis.

BACKGROUND: Diagnosing infected necrotizing pancreatitis (INP) may be challenging. The aim of this study was to determine the added value of routine fine-needle aspiration (FNA) in addition to clinical and imaging signs of infection in patients who underwent intervention for suspected INP. METHODS: We conducted a post hoc analysis of 208 consecutive patients from a prospective, multicenter database who underwent intervention because of suspected INP. In retrospect, 3 groups were constructed based on the patients preoperative characteristics: Clinical, imaging, and FNA. Patients in the clinical group had clinical signs of infection but no gas on preoperative computed tomography (CT) and no FNA performed before intervention. Patients in the imaging group had gas bubbles on the preoperative CT but no was FNA performed, whereas patients in the FNA group had a positive FNA before intervention. The reference standard for infection was the culture taken during the first intervention (either catheter drainage or necrosectomy). RESULTS: The initial intervention for INP was performed a median of 27 days (interquartile range, 20-39) after admission without difference between the 3 groups (P = .15). Infection was confirmed in 80% of 92 patients of the clinical group, in 94% of 88 patients of the imaging group, and in 86% of 28 patients of the FNA group (P = .07). Mortality was 19% and was not different between groups (P = .39). CONCLUSION: INP can generally be diagnosed based on clinical or imaging signs of infection. FNA may be useful in patients with unclear clinical signs and no imaging signs of INP.

To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.

Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis. After intestinal production, ammonia is detoxified by the liver. In liver failure, skeletal muscle and brain have been proposed to be alternative, although temporary, ammonia detoxifying organs. However, there is an increasing body of evidence that the kidney, in addition to the gut, is a pivotal organ determining systemic ammonia levels. In the last 20 years, it has been shown that the kidney can switch from an organ of systemic net ammonia production to a net ammonia excretion organ. The kidney plays a central role in the determination of ammonia levels. It is at least as important as the gut and could therefore serve as a target for new treatments for hepatic encephalopathy.

Fixation methods for electron microscopy of human and other liver.

For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.

A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study).

BACKGROUND: The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? METHOD/DESIGN: The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3 x 40 = 120 patients is calculated. DISCUSSION: The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. TRIAL REGISTRATION: ISRCTN44649165.

Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: a prospective multicenter study.

SUMMARY BACKGROUND DATA: The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. METHODS: We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 mumol/L] and/or dilated common bile duct) were analyzed separately. RESULTS: Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13-0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08-2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49-3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19-3.12, P = 0.734). CONCLUSIONS: Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.

Sacral neuromodulation in patients with fecal incontinence: a single-center study.

PURPOSE: Fecal incontinence is a psychologically devastating and socially incapacitating condition. Conventional treatment is likely to improve continence in many patients; however, there remains a group with persisting symptoms who are not amenable for a simple surgical repair. We evaluated the effect of sacral neuromodulation in patients with structurally intact sphincters after failure of conventional treatment. METHODS: Patients aged 18 to 75 years were evaluated. Incontinence was defined as involuntary loss of stool at least once per week, which was objectified by completion of a three-week bowel-habits diary during ambulatory electrode stimulation at the S3 or S4 foramen. Patients were qualified for permanent stimulation when showing a reduction of at least 50 percent in incontinence episodes or days. RESULTS: Seventy-five patients (66 females; mean age, 52 (range, 26-75) years) were treated. Three patients had partial spinal cord injury, two patients a previous low-anterior resection, and nine patients had a previous sphincter repair. Evaluation after trial screening showed that 62 patients (83 percent) had improved continence. Median incontinence episodes per week decreased from 7.5 to 0.67 (P < 0.01), median incontinence days per week from 4 to 0.5 (P < 0.01). The symptomatic response stayed unchanged after implantation of a permanent electrode and pacemaker in 50 patients. After a median follow-up of 12 months, this effect could be sustained in 48 patients. Anal manometry during stimulation showed no increase of sphincter pressures. CONCLUSIONS: Sacral neuromodulation is a feasible treatment option for fecal incontinence in patients with structurally intact sphincters.