Nicorandil‐induced penile ulcerations: a case series

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Partial nephrectomy is the standard treatment for the management of small renal masses, and laparoscopy has been widely used in this setting as it has all the principles of open procedures combined with the advantages of minimal invasiveness. Laparoscopic partial nephrectomy is feasible and has acceptable pathological results not only for small renal masses but also for large tumours, even if complication rate and ischemia time are still matters of debate.

OBJECTIVE

• ? To investigate the perioperative safety of laparoscopic partial nephrectomy (LPN) for large renal masses (>4 cm).

PATIENTS AND METHODS

• ? After Institutional Review Board approval, data from 100 consecutive patients who had undergone transperitoneal or retroperitoneal LPN at our institution from January 2005 to June 2009 were obtained from our prospectively maintained database.
• ? The patients were divided into two groups according to radiological tumour size: group A (67 patients) with tumours ≤4 cm and group B (33 patients) with tumours >4 cm.
• ? Demographic, perioperative and pathological data were evaluated.

RESULTS

• ? The two groups were comparable in terms of demographic data. Mean tumour size was 2.4 and 5 cm (P= 0.0001) for groups A and B, respectively. Group B tumours were more complex, as reflected by significantly more with a central location (P= 0.002), and by significantly more transperitoneal LPNs, pelvicalyceal repairs and longer warm ischaemia time (WIT; 19 vs 28 min).
• ? Complications were recorded in nine group A patients (13.4%) and nine group B patients (27.2%) (P= 0.09).
• ? There was no difference between preoperative and postoperative serum creatinine levels in either group, while a significant difference was found in postoperative estimated glomerular filtration rate between groups (P= 0.004).
• ? The incidence of carcinoma was comparable between the two groups.
• ? The incidence of positive surgical margins (PSMs) was 3.9% in group A, whereas no PSM was recorded in group B (P= 0.3).

CONCLUSIONS

• ? Laparoscopic partial nephrectomy for large tumours is feasible and has acceptable pathological results. However, the complication rate, in particular WIT, remains questionable.
• ? Further studies are required to better clarify the role of LPN in the management of tumours of this size.

     

J‐pouch vs side‐to‐end coloanal anastomosis after preoperative radiotherapy and total mesorectal excision for rectal cancer: a multicentre randomized trial

Aim Comparison of functional and surgical outcome of the J‐pouch with the side‐to‐end coloanal anastomosis after preoperative radiotherapy and total mesorectal excision in rectal cancer patients. Method In a multicentre study, patients with a carcinoma of the lower two‐thirds of the rectum were randomized to either a J‐pouch or a side‐to‐end reconstruction. Primary outcome was function of the neorectum 1 year after surgery. A functional outcome [COloREctal Functional Outcome (COREFO)] questionnaire, and two quality of life questionnaires (EORTC‐QLQ‐CR38 and SF‐36) were to be completed by all participants preoperatively, and 4 and 12 months postoperatively. Independent data managers recorded surgical outcome. A group size of 30 patients in each group was calculated based on a 15‐point difference of the COREFO scale. Results In total, 107 patients were randomized, 55 in the J‐pouch group and 52 in the side‐to‐end anastomosis group. The COREFO incontinence scale at 4 months and the total functional outcome at 4 and 12 months showed better results for the J‐pouch group in comparison with the side‐to‐end anastomosis group. The remaining COREFO scales (frequency, social impact, stool‐related aspects and bowel medication), surgical outcome (complications, reoperations, length of hospital stay, readmissions and mortality) and quality of life did not show significant differences between treatment groups. Conclusion The overall results of a coloanal J‐pouch and a side‐to‐end anastomosis are comparable, although functional results are slightly better with a J‐pouch. The side‐to‐end anastomosis is technically less demanding and therefore a justified alternative in sphincter‐saving surgery.     

Training model for end‐to‐side microvascular anastomosis in rat

End‐to‐side microsurgery is technically more challenging than end‐to‐end microvascular anastomosis. However, there is no ideal model to practice this exercise. An animal training model is described for practising this type of anastomosis.     

A natural history of weight change in men with prostate cancer on androgen‐deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Study Type – Harm (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Prior studies have shown that men undergoing ADT tend to gain weight, with a net increase in fat mass and decrease in bone density and lean body mass. We sought to characterize the natural history of weight gain on ADT by studying patients over a three‐year interval, finding that most weight gain occurs within the first year of initiating therapy. Furthermore, we confirm these prior findings in a more racially heterogeneous population of men, an important finding given the different outcomes of prostate cancer in black and white men.

OBJECTIVES

• ? To better understand the natural history of weight change with androgen‐deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
• ? Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight.

PATIENTS AND METHODS

• ? We identified 132 men in SEARCH who received ADT after radical prostatectomy.
• ? ‘Weight change’ was defined as the difference in weight before starting ADT (6 months before ADT) and the on‐ADT weight (between 6 and 18 months after starting ADT).
• ? In a subanalysis, baseline characteristics of weight‐gainers and ‐losers were analysed using univariate and multivariate analysis to test association with weight change.

RESULTS

• ? In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight.
• ? On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight‐gainers and ‐losers being +4.2 kg and ?2.4 kg, respectively.
• ? This compared with no significant weight change in the year before starting ADT (paired t‐test, change ?0.7 kg, P= 0.19) or in the second year on ADT (paired t‐test, change ?0.5 kg, P= 0.46) for 84 men in whom these additional weight values were recorded.
• ? There was no significant association between any of the features examined and weight change on univariate and multivariate analysis.

CONCLUSION

• ? In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter.

     

Peri‐operative management of patients with type‐2 diabetes mellitus undergoing non‐cardiac surgery using liraglutide,glucose–insulin–potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial

In this open‐label multicentre randomised controlled trial, we investigated three peri‐operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18–75 years with type‐2 diabetes mellitus undergoing non‐cardiac surgery. Patients were randomly allocated using a web‐based randomisation program to premedication with liraglutide (liraglutide group), glucose–insulin–potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l^?1. The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention‐to‐treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6–7.7 [4.2–13.5]) mmol.l^?1 vs. 7.5 (6.4–8.3 [3.9–16.6]) mmol.l^?1 (p = 0.026) and 7.6 (6.4–8.9 [4.7–13.2]) mmol.l^?1) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre‐operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre‐operative administration of liraglutide stabilised peri‐operative plasma glucose levels and reduced peri‐operative insulin requirements, at the expense of increased pre‐operative nausea rates.     

Efficacy and safety of rosuvastatin in late‐onset hypogonadism patients with dyslipidaemia

Rosuvastatin has been used for treatment of dyslipidaemia and metabolic syndrome, but the efficacy has not yet been tested in men with late‐onset hypogonadism (LOH). To assess and compare the efficacy and safety of rosuvastatin in men with dyslipidaemia with LOH and non‐LOH, a retrospective study was conducted in patients who received rosuvastatin 10 mg day^?1 from the men's health clinic. The primary endpoint was the change in low‐density lipoprotein (LDL)‐cholesterol (C) after 24 weeks of treatment. A total of 145 dyslipidaemic patients eligible for rosuvastatin treatment were enrolled and divided into LOH group (45.52%) and non‐LOH (54.48%) group. There were favourable changes in the lipid profiles. In the LOH group whose serum testosterone had been raised by testosterone administration, the favourable changes of the lipids were of similar magnitude as in the non‐LOH group. The percentage of patients reaching the target goal (LDL < 100 mg dL^?1) did not differ significantly between the group of non‐LOH and LOH men treated with testosterone. Side effects were noted in 1/145 men. It is concluded that rosuvastatin was safe and effective in lowering low‐density lipoprotein cholesterol in both non‐LOH and LOH dyslipidaemic patients whose serum testosterone levels had normalised.     

Nurse‐controlled analgesia (NCA) following major surgery in 10 000 patients in a children’s hospital

Background and Objectives: Patients who received NCA with morphine following major surgery between 1996 and 2008 at Great Ormond Street Hospital, London, UK, were prospectively studied in the postoperative period to determine effectiveness, morphine requirements, incidence of common side effects, and serious adverse events. Methods: The morphine NCA regimen and monitoring was according to standard hospital protocols. Data were collected prospectively and subsequently entered by trained personnel into a secure database. Patient demographics, effectiveness and satisfaction rates, morphine requirements, side effects, and serious complications were recorded. Results: 10 079 patients were included. The average age was 4 years old (range 1 day to 20.5 years, median 2.3 years). There were 510 neonates. The average NCA duration was 43.7 h. 1.8% of morphine NCAs were replaced by other methods because analgesia was unsatisfactory. Satisfaction ratings were ‘good’ or ‘very good’ for 98% of the remainder. Average daily morphine requirement (mcg·kg^?1·h^?1) was related to age, surgical category, and postoperative time. Side effects included PONV (25%), itching (9.4%), depression of respiration, and sedation (4.5%); incidences varied with age, morphine dose, and type of surgery. Serious, potentially life‐threatening adverse effects (SAE) were 0.4%. There were no deaths. SAE were significantly greater in neonates (2.5%), relative risk 9.4, P < 0.001. Morphine dose in neonates who experienced SAE was not significantly different from other neonates. Conclusion: NCA with morphine is an acceptable, safe, and effective method of postoperative analgesia for a wide range of ages and types of surgery in our practice. Morphine requirements increase with age, but there was also considerable inter‐individual variation within age groups. PONV, itching, sedation, and respiratory depression are expected side effects. SAE are uncommon but the incidence is greatest in neonates.     

Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study

OBJECTIVE: To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer. PATIENTS AND METHODS: Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method. RESULTS: In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%). CONCLUSIONS: IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.     

Symptom experience associated with immunosuppressive drugs after liver transplantation in adults: possible relationship with medication non‐compliance?

Symptom experience (occurrence and perceived distress) associated with side effects of immunosuppressive medications in organ transplant patients may well be associated with poorer quality of life and medication non-compliance. The aims of this study were: first, to assess symptom experience in clinically stable adult patients during long-term follow-up after liver transplantation; and second, to study the relationship between symptom experience and medication non-compliance. This cross-sectional study included 123 liver transplant patients. Symptom experience was assessed using the "Modified Transplant Symptom Occurrence and Symptom Distress Scale" (29-item version) at the annual evaluation. According to the duration of follow-up, patients were divided into a short-term (1-4 yr) and a long-term (5-18 yr) cohort. Medication non-compliance was measured using electronic monitoring. Results showed that increased hair growth was the most frequent symptom in both sexes. Symptom distress was more serious in women than in men. The most distressing symptom in women was excessive and/or painful periods, while in men this was impotence. Clear differences were revealed at item level between symptom occurrence and symptom distress in relationship with the two time cohorts and between sexes. No relationship was found between symptom experience and prednisolone non-compliance.     

The Society for Pediatric Anesthesia recommendations for the use of opioids in children during the perioperative period

Opioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years.     

Options for Decentralized Testing of Suspected Secondary Outbreaks of Foot‐and‐mouth Disease

This article reviews the options for use of virus detection techniques for decentralized testing of samples from suspected secondary outbreaks of foot‐and‐mouth disease (FMD). These options have been expanded by the advent of new tests including disposable lateral flow devices (LFDs) that detect viral proteins and portable RT‐PCR equipment that detects viral RNA. LFDs have been developed with similar sensitivity to antigen detection ELISA but with the ability to provide a result 1–30 min after the addition of epithelium or vesicular fluid. Portable RT‐PCR platforms are being developed that can detect FMD viral RNA in blood, epithelium or other materials with minimal sample processing and with high sensitivity, in as little as 60 min in some cases. These devices may be used on infected farms as pen‐side tests, in regional, local or mobile laboratories, or in National Reference Laboratories (NRL). Advantages and disadvantages of different testing options are considered to inform decisions on the optimal strategies for different national circumstances. Issues include validation and quality control, containment needs, availability of test devices and reagents, the decision tree for declaring an outbreak, training issues and provision of samples for subsequent viral characterization. Tests to confirm the diagnosis of the index case of an outbreak of FMD should continue to be carried out in the NRL.     

Differences in side‐effect duration and related bother levels between phosphodiesterase type 5 inhibitors

OBJECTIVE

To assess whether the longer half‐life of tadalafil is associated with longer lasting or more severe side‐effects than the other phosphodiesterase type 5 inhibitors (PDE‐5Is), as clinical trials have shown that the efficacy and safety of the three available are similar, but tadalafil has a half‐life four times longer than the other two drugs.

PATIENTS AND METHODS

Treatment‐naive men beginning PDE5‐I therapy were recruited from a specialist clinic. Data on the type and duration of drug‐associated side‐effects were collected prospectively. Levels of bother were assessed with a visual analogue scale (VAS). Differences in type, duration and bother of side‐effect were compared between drugs.

RESULTS

In all, 409 men provided data; there were no differences between drugs in the proportion of men responding, or the overall prevalence of side‐effects. The mean duration of side‐effects with tadalafil was 14.9 h, compared to 3.9 and 7.7 h for sildenafil and vardenafil. Of men taking tadalafil, 30% had side‐effects lasting >12 h. There were no differences in mean VAS scores between the drugs. Individual side‐effects caused similar levels of bother, except for facial flushing, which was less bothersome.

CONCLUSIONS

Men taking tadalafil are at risk of prolonged side‐effects, although levels of bother associated with these side‐effects are not significantly greater than those seen with short‐acting PDE5‐Is.     

Androgen‐suppression therapy for prostate cancer and the risk of death in men with a history of myocardial infarction or stroke

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

OBJECTIVE

To examine the effect of short‐course androgen‐suppression therapy (AST) before brachytherapy on all‐cause mortality (ACM) rates, stratified by the presence or absence of a history of myocardial infarction (MI) or stroke. AST is used to reduce prostate size to enable men with favourable‐risk prostate cancer to undergo brachytherapy, but no disease‐specific benefit has been reported for this practice, and AST use has been associated with an increased risk of ACM in some men with pre‐existing cardiovascular disease.

PATIENTS AND METHODS

The study comprised 12 792 men with favourable‐risk disease, i.e. a prostate‐specific antigen (PSA) level of <20 ng/mL, Gleason score ≤7 and clinical category ≤T2c, treated between 1991 and 2007 at community‐based medical centres with brachytherapy ± neoadjuvant AST. Multivariable Cox regression analysis was used to assess whether there were significant associations between AST use in men with a history of MI or stroke and the risk of ACM, adjusting for age, treatment year, and known prognostic factors of prostate cancer.

RESULTS

After a median (interquartile range) follow‐up of 3.8 (2.0–5.9) years there were 1557 deaths. The risk of ACM was lower in men with no history of MI or stroke than in those with this history, whether AST was used (adjusted hazard ratio 0.79, 95% confidence interval 0.67–0.92; P= 0.003) or not (0.74, 0.65–0.85; P < 0.001). However, men with a history of MI or stroke treated with AST had a greater risk of ACM than those not treated with AST (1.2, 1.05–1.38; P= 0.008).

CONCLUSION

The use of short‐course AST in men with a history of MI or stroke is associated with a greater risk of ACM in men with favourable‐risk prostate cancer.     

Pulmonary Embolism Complicating Human Chorionic Gonadotropin Treatment in a Patient with Type IV Hyperlipoproteinemia

Human chorionic Gonadotropin (HCG) therapy has been used beneficially in men with subfertility especially after varicocele surgery. Very few side effects have been observed in male patients. Herein, we report a case of pulmonary embolism in a male patient following the use of HCG. The patient was subsequently found to have type IV hyperlipoprotenemia. The etiology of the thrombo-embolic episode is conjectural, but this case emphasizes the need for stricter criteria of patient selection and screening for conditions that predispose to thrombo-embolism before starting HCG therapy.