Metaphylaxis, diet and lifestyle in stone disease

Objective: The most common urinary stones (calcium salts, uric acid) form due to genetic factors and lifestyle. This review describes why, if and how medication and lifestyle changes can reduce the risk of formation. Methods: Previous reports were reviewed to obtain information on three aspects of urolithiasis, i.e. epidemiology, mechanisms linking lifestyle and urolithiasis and lifestyle intervention for preventing urolithiasis. Results: Epidemiological evidence links the prevalence of urinary stone formation to general lifestyle factors. Detailed analysis has identified individual lifestyle elements that affect the risk of urinary stone formation. Currently there are several concepts that explain the mechanism of stone formation. Urinary markers like calcium, oxalate, phosphate, uric acid and urinary pH are involved in all these concepts. Many studies show that changing (combinations of) specific lifestyle elements has a favourable effect on these urinary markers. Based on this evidence, protocols have been developed that use a combination of these lifestyle changes and medication to prevent stone formation. In well-controlled studies where patients are optimally informed and continuously motivated, these protocols clearly reduce the stone formation rate. In general practice the result is less clear, because the time and tools are insufficient to maintain long-term patient compliance in the use of medication and lifestyle advice. Conclusion: The risk of stone formation can be reduced in general practice when the patient's compliance is optimised by providing individualised advice, continuous information, and feedback and incorporation of the advice into a regular lifestyle. The use of 'e-tools' might enable this without increasing the time required from the physician

Influence of sildenafil on blood oxygen saturation of the obstructed bladder

Background: Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction. Methods. Thirty-two guinea pigs; sham operated (n = 8), sham operated + SC (n = 8), urethrally obstructed (n = 8) and urethrally obstructed + SC (n = 8) were studied during an 8 week period. BOS of the bladder wall was measured by differential path-length spectroscopy (DPS) before obstruction, at day 0, and at week 8. The bladder function was evaluated by urodynamic studies every week. Results: Before surgery and after sham operation all study parameters were comparable. After sham operation, bladder function and BOS did not change. In the obstructed group the urodynamic parameters were deteriorated and BOS was decreased. In the group obstruction + SC, bladder compliance remained normal and overactivity occurred only sporadic. BOS remained unchanged compared to the sham group and was significantly higher compared to the obstruction group. Conclusions: In an obstructed bladder the loss of bladder function is accompanied by a significant decrease in BOS. Treatment of obstructed bladders with SC yields a situation of high saturation, high bladder compliance and almost no overactivity. Maintaining the microcirculation of the bladder wall might result in better bladder performance without significant loss of bladder function. Measurement of BOS and interventions focussing on tissue microcirculation may have a place in the evaluation / treatment of various bladder dysfunctions

Is the impaired flow after hypospadias correction due to increased urethral stiffness?

Purpose: A low flow rate without clinical symptoms is commonly found in boys after hypospadias correction. Urethral calibration usually shows no abnormalities. We investigated whether this flow rate impairment might be caused by increased neo-urethral wall-stiffness. Methods: From Polyvinyl Alcohol cryogel two models of the urethra were made, a hypospadias model and a control model. Both models had a constant and equal inner diameter and equal compliance. The hypospadias model had a less compliant distal segment mimicking the distal neo-urethra after hypospadias correction. In both models flow rate was recorded as a function of bladder pressure. To test whether the length of the less compliant segment had an effect on the flow rate, both models were shortened by cutting off 1 cm segments. Results: In a physiological range of bladder pressures (10 - 130 cmH2O) the mean flow rate(± 1sem) in the hypospadias model was 2.8± 0.3 ml/s, significantly lower (p < .05) than in the control model (5.4 ± 0.6 ml/s). Shortening of the hypospadias model showed some increase in flow rate, however not statistically significant. In the control model there was also no significant variation in flow rate. Conclusion: We showed that a low compliant segment of a urethral model reduces the flow rate. Extrapolating these results to asymptomatic boys with a low urinary flow rate after hypospadias repair might justify a watchful waiting policy.RePub contains a preprint of the article. See: http://www.intl.elsevierhealth.com/journals/jpu

Diagnosis and treatment of hepatocellular adenoma in the Netherlands: Similarities and differences

Background: The diagnosis of hepatocellular adenoma (HA) has a great impact on the lives of young women and may pose clinical dilemmas to the clinician since there are no standardized protocols to follow. We aimed to establish expert opinions on diagnosis and treatment of HA by collecting data from a nationwide questionnaire in the Netherlands. Methods: A questionnaire was sent to 20 Dutch hospitals known to offer hepatologic and surgical experience on liver tumours. Results: 17 hospitals (85%) responded to the questionnaire. Annually, a median of 52 patients presented with a solid liver tumour. In 15 (88%) hospitals, hepatic adenomas were diagnosed with contrast-enhanced, multiphase spiral CT or MRI. In 2 (12%) hospitals, histology was required as part of a management protocol. Surveillance after withdrawal of oral contraceptives was the initial policy in all clinics. MRI, CT or ultrasound was used for follow-up. Criteria for surgical resection were a tumour size >5 cm and abdominal complaints. In 5 (29%) hospitals, patients were dismissed from follow-up after surgery. In complex cases (e.g. large, multiple or centrally localized lesions, a wish for pregnancy), the tre

Management of hepatocellular adenoma during pregnancy

Background & Aims: Hepatocellular adenoma in pregnant women requires special considerations because of the risk of hormone induced growth and rupture. To prevent these potential lethal complications, pregnancy is either often discouraged or the surgical resection of large adenomas is recommended. It may be questioned whether it is justified to deny a young woman a pregnancy, as the biological behaviour of hepatocellular adenoma may be less threatening than presumed. In this study we establish the management of hepatocellular adenoma during pregnancy based on our own experience and literature. Methods: Twelve women with documented hepatocellular adenoma were closely monitored during a total of 17 pregnancies between 2000 and 2009. Their files were reviewed. Results: In four cases, hepatocellular adenomas grew during pregnancy, requiring a Caesarean section in one patient (two pregnancies) at 36 and 34 weeks because of an assumed high risk of rupture. In one case radiofrequency ablation therapy was applied in the first trimester to treat a hormone sensitive hepatocellular adenoma, thereby excluding potential growth later in pregnancy. No intervention was performed in the other 14 cases and all pregnancies had an uneventful course with a successful maternal and fetal outcome. Conclusions: A "wait and see" management may be advocated in pregnant women presenting with a hepatocellular adenoma. In women with large tumours or in whom hepatocellular adenoma had complicated previous pregnancies, surgical resection may be recommended. In women with smaller adenomas it may no longer be necessary to discourage pregnancy

Volume–outcome relationship of liver surgery: a nationwide analysis

Background: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30-day or in-hospital mortality. Results: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion: Hospital volume and postoperative outcomes were not associated

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

Background: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs. Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien–Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy. Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51–64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29–52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed un

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017