PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports.

In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

Implementing universal rifampicin testing for TB in Pakistan: results and implications for the TB response.

SETTING: A large specialised chest hospital in Pakistan.OBJECTIVE: To study outcomes of comprehensive Xpert® MTB/RIF and universal rifampicin testing.DESIGN: A hospital-based, 3-year retrospective record review of registered TB patients.RESULTS: During the study, 11 744 TB patients were registered when the number of annual notifications remained stagnant. Xpert use increased dramatically in adults with pulmonary TB (PTB) from less than 1% tested with Xpert alone in 2016, to 81.6% by 2018. Significant increases were seen in bacteriologically confirmed PTB in adults from 64% to 77.3% (P < 0.001). No remarkable changes were seen in testing and confirmation of PTB in children or extrapulmonary TB. Significantly lower (P < 0.001) rifampicin resistance (RR) was observed among those with smear-negative compared to those with smear-positive results among new (1.0% vs. 5.1%) and previously treated PTB cases (2.0% vs. 14.4%). Most importantly, a significant decline in RR was observed among previously treated individuals, from 15.4% (95%CI 12.2-19.0) to 8.6% (95%CI 6.6-11.0) during the study. A decrease in RR was also documented in newly diagnosed PTB patients, but this was not statistically significant.CONCLUSION: Universal rifampicin testing is feasible in adult PTB patients; a decline in RR was seen among previously treated individuals with PTB.

Chorioamnionitis induces enteric nervous system injury: effects of timing and inflammation in the ovine fetus.

BACKGROUND: Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. METHODS: We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. RESULTS: Four days of IA LPS exposure causes a decreased PGP9.5- and S100ß-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. CONCLUSIONS: The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies.

Long-term functional outcomes and quality of life in patients with Hirschsprung's disease.

BACKGROUND: It is unclear whether functional outcomes improve or deteriorate with age following surgery for Hirschsprung's disease. The aim of this cross-sectional study was to determine the long-term functional outcomes and quality of life (QoL) in patients with Hirschsprung's disease. METHODS: Patients with pathologically proven Hirschsprung's disease older than 7 years were included. Patients with a permanent stoma or intellectual disability were excluded. Functional outcomes were assessed according to the Rome IV criteria using the Defaecation and Faecal Continence questionnaire. QoL was assessed by means of the Child Health Questionnaire Child Form 87 or World Health Organization Quality of Life questionnaire 100. Reference data from healthy controls were available for comparison. RESULTS: Of 619 patients invited, 346 (55·9 per cent) responded, with a median age of 18 (range 8-45) years. The prevalence of constipation was comparable in paediatric and adult patients (both 22·0 per cent), and in patients and controls. Compared with controls, adults with Hirschsprung's disease significantly more often experienced straining (50·3 versus 36·1 per cent; P = 0·011) and incomplete evacuation (47·4 versus 27·2 per cent; P < 0·001). The prevalence of faecal incontinence, most commonly soiling, was lower in adults than children with Hirschsprung's disease (16·8 versus 37·6 per cent; P < 0·001), but remained higher than in controls (16·8 versus 6·1 per cent; P = 0·003). Patients with poor functional outcomes scored significantly lower in several QoL domains. CONCLUSION: This study has shown that functional outcomes are better in adults than children, but symptoms of constipation and soiling persist in a substantial group of adults with Hirschsprung's disease. The persistence of defaecation problems is an indication that continuous care is necessary in this specific group of patients.

Choledochal Malformation in Children: Lessons Learned from a Dutch National Study.

INTRODUCTION: A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in childhood. METHODS: All pediatric patients who underwent a surgical procedure for type I-IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (<30 days) and long-term (>30 days) complications were studied retrospectively. RESULTS: Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0-17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up. CONCLUSION: Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery.

The proportion of postmenopausal breast cancer cases in the Netherlands attributable to lifestyle-related risk factors.

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2-27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3-11.3) for overweight/obesity, 6.6 % (95 % CI 5.2-8.0) for alcohol consumption, 5.5 % (95 % CI 4.0-7.0) for physical inactivity, 4.6 % (95 % CI 3.3-6.0) for smoking and 3.2 % (95 % CI 1.6-4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.

Rectovaginal fistula: a new technique and preliminary results using collagen matrix biomesh.

BACKGROUND: A rectovaginal fistula (RVF) is a debilitating condition that is difficult to treat. Many available techniques are invasive and involve extensive surgery. A local procedure with good closure rates would be preferable as a first step in the treatment of RVF. The aim of this study was the development of a local technique for the closure of RVF with good closure rates to prevent the use of more invasive procedures. METHODS: This was a pilot study. Patients with RVF who had undergone multiple operations in the pelvic area, local radiotherapy, chemotherapy or had been diagnosed with Crohn's disease were included in the study. All had a history of surgery for RVF. A cross-linked collagen matrix biomesh was placed in the rectovaginal septum using a transperineal or a transvaginal approach. The main outcome measure in this study was the closure rate reported as absence of the fistula at 1 year. RESULTS: Twelve patients were included in the study. Absence of fistula at 1 year was 0.64 (95 % confidence interval 0.30-0.85). Three patients (25.0 %) developed a recurrence, two were reoperated on with a gracilis flap transposition, and one was treated with laparoscopic ligation. In one patient (8.3 %), the fistula failed to close within 3 months after the mesh placement. CONCLUSIONS: Our technique shows promising results. A local and simple technique with acceptable closure and morbidity rates, like our local repair with biomesh, would be ideal as a first step in treating RVFs. Long-term results are needed.

Multidrug-resistant tuberculosis in Uzbekistan: results of a nationwide survey, 2010 to 2011.

Multidrug-resistant tuberculosis (MDR-TB; resistance to at least rifampicin and isoniazid) is a global public health concern. In 2010­2011, Uzbekistan, in central Asia, conducted its first countrywide survey to determine the prevalence of MDR-TB among TB patients. The proportion of MDR-TB among new and previously treated TB patients throughout the country was measured and risk factors for MDR-TB explored. A total of 1,037 patients were included. MDR-TB was detected in 165 treatment-naïve (23.2%; 95% confidence interval (CI) 17.8%­29.5%) and 207 previously treated (62.0%; 95% CI: 52.5%­70.7%) patients. In 5.3% (95% CI: 3.1%­8.4%) of MDR-TB cases, resistance to fluoroquinolones and second-line injectable drugs (extensively drug resistant TB; XDR-TB) was detected. MDR-TB was significantly associated with age under 45 years (adjusted odds ratio: 2.24; 95% CI: 1.45­3.45), imprisonment (1.93; 95% CI: 1.01­3.70), previous treatment (4.45; 95% CI: 2.66­7.43), and not owning a home (1.79; 95% CI: 1.01­3.16). MDR-TB estimates for Uzbekistan are among the highest reported in former Soviet Union countries. Efforts to diagnose, treat and prevent spread of MDR-TB need scaling up.

A prospective non-randomized two-centre study of patients with passive faecal incontinence after birth trauma and patients with soiling after anal surgery, treated by elastomer implants versus rectal irrigation.

AIM: This study is a prospective evaluation of patients with passive faecal incontinence and patients with soiling treated by elastomer implants and rectal irrigation. PATIENTS AND METHODS: Patients with passive faecal incontinence after birth trauma resulting from a defect of the internal sphincter and patients with soiling after previous anal surgery were included. All patients underwent endo-anal ultrasound, magnetic resonance imaging, and anal manometry. The patients with passive faecal incontinence were initially treated by anal sphincter exercises and biofeedback therapy during half a year. The patients completed incontinence scores, a quality of life questionnaire, and a 2-week diary card. RESULTS: The elastomer group consisted of 30 males and 45 females with a mean age of 53 years (25-77). The rectal irrigation group consisted of 32 males and 43 females with a mean age of 50 years (25-74). At 6 months follow-up, 30 patients with soiling of the rectal irrigation group and only nine patients of the elastomer group were completely cured (p = 0.02). Only three patients with passive faecal incontinence were cured in the rectal irrigation group and none in the elastomer group. Three distal migrations of elastomer implants required removal at follow-up. CONCLUSIONS: After patients had performed anal sphincter exercises, no clear improvement of passive faecal incontinence was obtained by elastomer implants or rectal irrigation. However, rectal irrigation is far more effective than elastomer implants in patients with soiling.

Transvaginal posterior colporrhaphy combined with laparoscopic ventral mesh rectopexy for isolated Grade III rectocele: a prospective study of 27 patients.

AIM: The aim of this study was to evaluate prospectively transvaginal posterior colporrhaphy (TPC) combined with laparoscopic ventral mesh rectopexy (LVR) in patients with a symptomatic isolated rectocele. METHOD: Patients with these complaints underwent dynamic and static MRI. All consecutive patients with a Grade III (4 cm or more) rectocele and without internal/external rectal prolapse, enterocele and external sphincter damage were operated on. The patients completed the Obstructed Defecation Syndrome (ODS) score and the Cleveland Clinic Incontinence Score (CCIS). All tests were repeated after treatment. Dynamic disorders of the pelvic floor detected by MRI were recorded. RESULTS: In 27 patients [median age 67 (46-73) years], TPC combined with LVR was feasible. Complications were limited to port site infection in two patients. Sexual discomfort (n = 8) due to prolapse diminished in six (75%) patients and in one (4%) de novo dyspareunia developed after treatment. The median follow-up was 12 (10-18) months. The median CCIS was 12 (10-16) before treatment and 8 (7-10) after (P < 0.0001). The median ODS score was 19 (17-23) before and 6 (3-10) after treatment (P < 0.0001). There was no change in urinary symptoms. CONCLUSION: TPC combined with LVR for obstructed defaecation and faecal incontinence in patients with Grade III rectocele significantly relieves the symptoms of these disorders.

Sacral nerve modulation for defaecation and micturition disorders in patients with spina bifida.

AIM: Sacral nerve modulation is a well accepted method for the treatment of defaecation disorders and voiding dysfunction. Results of sacral nerve modulation in patients with spinal cord lesions are not well assessed, but preliminary results look poor. Therefore, the purpose of this study was to assess the effectiveness of sacral nerve modulation for defaecation disorders and voiding dysfunction in patients with spina bifida. METHOD: Consecutive patients with spina bifida suffering from a myelomeningocele and combined faecal and urinary functional disorders that were eligible for peripheral nerve evaluation (PNE) were studied. A permanent sacral nerve modulation implantation was performed after successful PNE. RESULTS: Ten patients (four female) were included in this study with a median age of 26.4 (range 11.1-41.0) years. In two the PNE was not possible. The median faecal incontinence days (6.0 vs 3.5) and episodes (8.5 vs 3.5) per 21 days decreased significantly during the 3-week period of PNE (P = 0.033). Only 3/10 (30%) patients had a more than 50% improvement and proceeded to a permanent sacral nerve modulation implantation. In one patient it was not possible to perform the permanent implant. CONCLUSION: Preliminary results of sacral nerve modulation in a subgroup of spina bifida patients with combined faecal and urinary functional disorders look promising, but long-term results in larger patient groups need to be studied.

Staged Mucosal Advancement Flap versus Staged Fibrin Sealant in the Treatment of Complex Perianal Fistulas.

Background. In this prospective randomised study, the staged mucosal advancement flap is compared with staged fibrin sealant application in the treatment of perianal fistulas. Methods. All patients with high complex cryptoglandular fistulas were randomised to closure of the internal opening by a mucosal advancement flap (MF) or injection with fibrin sealant (FS) after treatment with setons. Recurrence rate and incontinence disorders were explored. Results. The MF group (5 females and 10 males) with a median age of 51 years and a median followup of 52 months. The FS group (4 females and 11 males) with a median age of 45 years and a median followup of 49 months. Three (20%) patients of the MF group had a recurrent fistula compared to 9 (60%) of the FS group (P = 0.03). No new continence disorders developed. Conclusion. Staged FS injection has a much lower success rate compared to MF.

Conservative treatment of patients with faecal soiling.

PURPOSE: A prospective evaluation of fifty patients with faecal soiling but normal sphincter function treated by a conservative treatment algorithm. PATIENTS AND METHODS: Between January 2010 and January 2011, 50 consecutive patients of two different clinical centres, with faecal soiling and normal anorectal function as assessed by endoanal ultrasound, MRI and anal manometry, were eligible for the purpose of this study. All patients started the therapy by psyllium (PS) and a fibre-rich diet daily after 2 months followed by rectal irrigation (RI) in case of incomplete response and after 4 months by 4 g colestyramine (CO), respectively. The patients completed the Vaizey incontinence score and a 2-week diary card. All tests were performed repeated after 2, 4 and 8 months, respectively. RESULTS: The study group consisted of 41 men and 9 women and a mean age of 38 years (21-70). The soiling complaints resolved completely in 37 (79%) patients. After treatment with PS, RI and CO, 12 (24%) patients, 24 (73%) patients and 1 (79%) patient, respectively, resolved completely of faecal soiling. Average weekly soiling frequency, the amount of patients wearing pads daily and the Vaizey incontinence score diminished significantly after treatment with psyllium and after treatment with rectal irrigation (P < 0.001). CONCLUSION: Conservative treatment focussed on complete evacuation or clearing the anorectal canal is effective in the treatment of patients with faecal soiling.

Sacral neuromodulation: long-term outcome and quality of life in patients with faecal incontinence.

AIM: Since 1994 sacral neuromodulation (SNM) has increasingly been used for the treatment of faecal incontinence, but no long-term data in a large group of patients have so far been published. We report long-term outcome and quality of life in the first 50 patients treated by permanent SNM for faecal incontinence. METHOD: We began to use SNM in 2000. Data from the first 50 patients with faecal incontinence who underwent permanent SNM are presented. Efficacy was assessed using a bowel diary and the Quality of Life score was assessed by the Faecal Incontinence Quality of Life questionnaire (FIQOL) and the standard short form health survey questionnaire (SF-36). RESULTS: Over a median follow up of 7.1 (5.6-8.7) years, forty-two (84%) patients had an improvement in continence of over 50%. Median incontinent episodes and days of incontinence per week decreased significantly during follow up (P<0.002). Improvement was seen in all four categories of the FIQOL scale and in some domains of the SF-36 QOL questionnaire. There were no statistically significant changes in the median resting and squeeze anal canal pressures. CONCLUSION: Initial improvement in continence with SNM was sustained in the majority of patients, with an overall success rate of 80% after a permanent implant at 7 years.

The role of reprogramming in sacral nerve modulation for faecal incontinence.

AIM: After implantation of a sacral nerve modulation (SNM) device for faecal incontinence (FI), patients are subjected to a rigid follow-up schedule. If symptoms recur, it may be necessary to reprogramme the stimulation parameters of the device. The aims of this study was to assess the need for reprogramming in patients with an SNM implant for FI. METHOD: All patients who received a permanent SNM implant for FI from January 2000 to February 2008 were included in this study. Patients were subjected to a rigid follow-up schedule at 1, 3, 6 and 12 months, and yearly thereafter. Stimulator settings of the SNM device and changes made at every visit were collected and added to the database, and the number of patients in whom the stimulation parameter settings needed reprogramming was determined. RESULTS: A total of 155 patients (11 men) were analysed. The mean age (± standard deviation) of the patients was 57.7 ± 11.9 years. Median follow-up was 28.1 (range: 1.0-93.6) months. The mean voltage increased significantly from 1.8 V at 1 month to 2.0 V at 3 months. Thirty-nine (25.2%) patients required no reprogramming of their SNM implant during any of their follow-up visits; however, 51 (32.9%) patients required reprogramming at 1-25% of their visits, 42 (27.1%) patients at 26-50% of their visits, 14 (9.0%) patients at 51-75% of their visits and nine (5.8%) patients at 76-100% of their visits. CONCLUSION: Physicians and patients need to be aware of the fact that reprogramming of the SNM stimulator needs to be carried out at least once during follow-up in the majority of patients. Trained physicians or specialist nurses are imperative to ensure effective follow-up and appropriate SNM reprogramming.

Autologous platelet-derived growth factors (platelet-rich plasma) as an adjunct to mucosal advancement flap in high cryptoglandular perianal fistulae: a pilot study.

AIM: The aim of this study was to explore autologous platelet-rich plasma as an adjunct to the staged mucosal advancement flap in the treatment of perianal fistulae. METHOD: Between February 2006 and May 2007, 10 patients with fistula tracts transversing from the middle-third or upper part of the anal sphincter were treated for at least 3 months with noncutting setons prior to definitive closure by autologous platelet-rich plasma as an adjunct to a mucosal advancement flap. Five patients smoked tobacco. RESULTS: The study group consisted of six women and four men with a median age of 44 (range 30-75) years and a median follow up of 26 (range 17-32) months. One (10%) patient had a recurrent fistula. No new continence disorders developed after definitive treatment in both groups. CONCLUSION: Platelet-rich plasma as an adjunct to a staged mucosal advancement flap for the treatment of perianal cryptoglandular fistulae is a promising treatment modality and seems to establish a high healing rate.

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.

BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.

Sacral neuromodulation: does it affect the rectoanal angle in patients with fecal incontinence?

BACKGROUND: In the past decade numerous studies have been published on the successful treatment of fecal incontinence with sacral neuromodulation (SNM). The underlying mechanism of action for lower bowel motility disorders has been unclear. In the present study, the effect of SNM on the rectoanal angle in patients with fecal incontinence was investigated. PATIENTS AND METHODS: In 12 consecutive patients who qualified for SNM an X-defecography study was performed before SNM and at 6 months after permanent implant. Three single lateral rectal views were taken: one during rest, one during squeeze, and one during Valsalva's maneuver, after which the patient was asked to evacuate as rapidly and completely as possible during lateral fluoroscopy. At 6 months two further defecography studies were performed, one during stimulation with the pacemaker on and one with the pacemaker off. RESULTS: The defecography studies showed that the rectoanal angle decreased during rest, squeeze, and Valsalva's maneuver. A slight increase in rectoanal angle was seen during defecation. However, the differences did not reach statistical significance. Sacral neuromodulation improved fecal continence significantly in all patients at 6 months. Median incontinence episodes per week decreased from 6.2 to 1.0 (P = 0.001), and incontinent days per week decreased from 3.7 to 1.0 (P = 0.001) with SNM. There were no significant changes in the median resting and squeeze anal canal pressures, 46.5 versus 49.7 mmHg and 67.1 versus 72.3 mmHg, respectively. Median stimulation amplitude at follow-up was 2.7 V (range: 0.9-5.3 V). CONCLUSIONS: Rectoanal angle did not decrease significantly in patients with fecal incontinence during SNM.

A prospective multicentre study to investigate percutaneous tibial nerve stimulation for the treatment of faecal incontinence.

AIM: Percutaneous tibial nerve stimulation (PTNS) is a minimal invasive treatment that can be performed in the outpatient clinic. This is a pilot study to investigate PTNS in the treatment of faecal incontinence. METHOD: Percutaneous tibial nerve stimulation was performed by insertion of a needle electrode near the posterior tibial nerve. Patients were treated twice a week. Evaluation of faecal incontinence and quality of life was performed at baseline, 6 weeks, 3 months, 6 months and 1 year. Quality of life was estimated using SF-36 and FIQL questionnaires. RESULTS: A total of 22 patients were included. The mean age was 60.4 ± 11.7 years. After 6 weeks, 18 continued the treatment; 13 patients had a > 50% decrease in incontinence episodes. Overall incontinence episodes fell from 19.6 ± 21.0 at baseline to 9.9 ± 15.5 (P = 0.082) at 6 weeks and to 3.6 ± 4.8 (P = 0.029) at 1 year. Postponement time and quality of life increased significantly during follow up. CONCLUSION: Percutaneous tibial nerve stimulation is simple and can be used in the outpatient setting. Good results can be obtained and sustained during maintenance treatment.

Optimisation of a green gas supply chain--a review.

In this review the knowledge status of and future research options on a green gas supply based on biogas production by co-digestion is explored. Applications and developments of the (bio)gas supply in The Netherlands have been considered, whereafter literature research has been done into the several stages from production of dairy cattle manure and biomass to green gas injection into the gas grid. An overview of a green gas supply chain has not been made before. In this study it is concluded that on installation level (micro-level) much practical knowledge is available and on macro-level knowledge about availability of biomass. But on meso-level (operations level of a green gas supply) very little research has been done until now. Future research should include the modeling of a green gas supply chain on an operations level, i.e. questions must be answered as where to build digesters based on availability of biomass. Such a model should also advise on technology of upgrading depending on scale factors. Future research might also give insight in the usability of mixing (partly upgraded) biogas with natural gas. The preconditions for mixing would depend on composition of the gas, the ratio of gases to be mixed and the requirements on the mixture.