Feasibility of a modified Atkins diet in glioma patients during radiation and its effect on radiation sensitization.

Background: Gliomas are the most dreaded primary brain tumour because of their dismal cure rates. Ketogenic-type diets (kds) are high-fat, low-protein, and low-carbohydrate diets; the modified Atkins diet (mad) is a less-stringent version of a kd that still generates serum ketones in patients. The purpose of the present study was to retrospectively examine the feasibility of attaining ketosis and the safety of the mad in patients undergoing radiation and chemotherapy treatment for glioma. The rate of pseudoprogression (psp) after treatment was also assessed as a marker of radiation sensitization. To our knowledge, this dataset is the largest published relating to patients with glioma undergoing kd during radiation and chemotherapy. Methods: We retrospectively studied 29 patients with grades ii-iv astrocytoma following the mad during standard radiation and chemotherapy. Feasibility of attaining ketosis was assessed though levels of beta hydroxybutyrate in blood. Pre- and post-radiation magnetic resonance images were evaluated for psp by a neuroradiologist blinded to patient data. Results: In the 29 patients who started the mad during radiation, ketosis was achieved in all 29 (100%). No serious adverse events occurred secondary to the mad. Of those 29 patients, 19 had glioblastoma multiforme. Of the latter 19 patients, 11 (58%) showed psp after mad and radiation and temozolomide therapy. Conclusions: A modified Atkins diet is feasible and safe for glioma patients during radiation and chemotherapy treatment. The mad and resulting ketosis could play a role as a radiation sensitizer.

Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

BACKGROUND: Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. AIM: To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. METHODS: We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. RESULTS: Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. CONCLUSIONS: Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis.

Experiences of surgical continence management approaches for cloacal anomalies: a qualitative analysis based on 6 women.

STUDY OBJECTIVE: The aim of this qualitative study was to gain insight into health care experiences of young women diagnosed with cloacal anomalies, with a special focus on continence management. DESIGN: Qualitative analysis of one-to-one interviews. SETTING: A tertiary center for congenital anomalies of the urogenital tract in London. PARTICIPANTS: Six women aged 16 to 24 with cloacal anomalies. INTERVENTIONS: Tape-recorded one-to-one semi-stuctured interviews with a skilled interviewer. MAIN OUTCOME MEASURE(S): The taped interviews were transcribed and analyzed verbatim using interpretative phenomenological analysis according to the research question. Organizing themes across all of the accounts were identified. RESULTS: Two organizing themes concerning our research interests are summarized. The first theme Personal Agency in the Hands of Experts focuses on the interviewees' appreciation of their life-saving surgical care and their involvement in treatment decisions. The second theme Compromises and Trade-Offs focuses on what it was like to live with the more traditional versus the more advanced continence methods. Reliability emerged as a key priority in terms of continence treatment outcome. Gratitude may have interfered with the women's honest communications during treatment decision and evaluation consultations. CONCLUSIONS: A more developed approach to communication about the complex interventions proposed, founded on a nuanced understanding of users perspectives, can enhance informed decision making about continence management approaches. Despite these specific gaps, the interviewees were appreciative of their care and optimistic about life.

The new oral anticoagulants: practical management for patients attending for endoscopic procedures.

Guidelines published by the British Society of Gastroenterology have standardised the care of patients attending for endoscopy procedures, taking aspirin, clopidogrel and warfarin. Two new oral anticoagulant drugs, Rivaroxaban and Dabigatran, are licensed and National Institute of Clinical Excellence (NICE) approved for use in the UK. Unlike warfarin, these drugs do not require regular monitoring, and are at least as effective in preventing stroke in non-valvular atrial fibrillation. As such, they are likely to become popular among patients and clinicians alike. This paper summarises the practical management of patients taking these drugs attending for endoscopic procedures.

[Patients' acceptance of urinary diversion. The pouch of Sisyphus]. / Aspekte der Akzeptanz von Harnableitung: Der Pouch des Sisyphos.

It is important that any patient with a urinary diversion can accept the psychological impact alongside the surgical and physical aspects. However, there are currently no validated methods or instruments available to allow direct measurement of this phenomenon in these patients. Health-related quality of life (HRQoL) is often high following different types of urinary diversion-this may suggest a high acceptance level and thus may act as a secondary end point. Such an assessment is a retrospective validation of successful patient selection, allowing us to redirect the nihilistic misinterpretation that urologists should return to offering ileal conduits as a standard. In modern urinary diversion, high patient acceptance develops from comprehensive counselling providing a realistic expectation, careful patient-to-method-matching, strict adherence to surgical detail during the procedure and a meticulous lifelong follow-up. Coping strategies, disease-related social support and confidence in the success of treatment are among other factors which contribute to acceptance of urinary reconstruction as either independent or combined factors. Significant experience is required in every respect, as misjudgement and mistakes in any of these issues may be detrimental to the patients' health. It should be acknowledged that there is no 'best' urinary diversion in general terms. A reconstructive surgeon must have all techniques available and choices need to be tailored to the individual patient.

False-positive pregnancy tests following enterocystoplasty.

People with major congenital urological or neurological malformations invariably require bladder reconstruction with enterocystoplasty in early childhood. The improvement of the surgical management of these children has reflected significantly on their life expectancy. As a result, more young people with enterocystoplasty are being transitioned to adolescent clinics where they receive the usual counselling about sexual health and pregnancy risks. However, the possibility of false-positive urinary pregnancy tests in these young women remains an overlooked but essential message. The lack of awareness about this fact can result in significant patient anxiety and the potential for unnecessary interventions as exemplified by the three cases we have encountered.

Supra-vesical urinary diversion and ureteric re-implantation for malignant disease.

Supra-vesical diversion or ureteric reconstruction is indicated for fistulae from the bladder or ureter, urinary incontinence, painful frequency and for end-stage renal failure due to obstructive uropathy. In a palliative setting, conservative measures, such as an indwelling catheter or ureteric stents, should be tried first. Open or laparoscopic surgery should be considered if these measures fail. For a patient who is leaking urine or has a very painful bladder, such surgery may well be justified, even very close to the end of life, as the symptoms are so unpleasant. When the problem is of end-stage renal failure that may be symptomless, the decision is more difficult; the patient may only gain a few months of life with no change in symptoms in return for the major surgery. The options available include cutaneous diversion either by ureterostomy or conduit and reconstruction either by re-implanting a ureter into the bladder or transuretero-ureterostomy. A laparoscopic approach may be possible in many cases.

When ascites is not ascites.

The case is reported of a patient presenting with ascites and acute renal failure resulting from spontaneous rupture of the urinary bladder, 30 years after the successful initial treatment of childhood rhabdomyosarcoma. The delay in the presentation until the patient began to experience the symptoms due to urinary ascites, the diagnostic dilemma because of the rarity of the condition, and the possible aetiologies are discussed.

Adolescent urology: A challenge for adult urologists.

The medical care of adolescents has become a growth area in many disciplines. There are two major aspects. Firstly, adolescents have specific medical and emotional needs which are not fulfilled either by paediatric or by adult specialists. Secondly, some childhood problems, particularly the congenital deformities, have no equivalent in adult life and so lifelong care is mandatory. Renal damage, especially dysplasia and scarring, leads to a substantial risk of early onset hypertension and, occasionally, to renal failure. Bladder outlet obstruction in utero, such as from a posterior urethral valve, causes irreversible changes to the wall that will act adversely on the kidneys in adolescence or early adulthood. The incidence of renal failure in early adulthood is about 36%. Bladder reconstruction with bowel has been very beneficial in preventing renal failure and improving continence. Life long follow-up is needed because of the high incidence of complications. These include stones, hyperchloraemic acidosis, perforation, anastomotic stenosis and, possibly, cancer. Patients have a normal expectation of sexuality and fertility. Their desires cannot always be achieved but they require considerable emotional and surgical support.

99mTechnetium-mercaptoacetyltriglycine scintigraphy with full bladder in patients with severe bladder dysfunction.

PURPOSE: We evaluated 99mtechnetium-mercaptoacetyltriglycine scintigraphy for detecting threshold bladder volume at which upper tract obstruction occurs in patients with bladder dysfunction. MATERIALS AND METHODS: A total of 24 patients 19 to 74 years old with severe bladder dysfunction who underwent 99mtechnetium-mercaptoacetyltriglycine scintigraphy and videocystometrogram in a 4-year period were selected for retrospective study. 99mTechnetium-mercaptoacetyltriglycine scintigraphy was done with a full bladder with a mean instilled volume of more than 850 ml saline. In patients in whom an obstructed renal outflow pattern was observed saline was drained at a rate of 100 ml every 5 minutes while dynamic imaging was performed. If results were abnormal, the study was repeated with an empty bladder. Differential function, parenchymal transit time index and outflow efficiency were calculated. RESULTS: Of the 24 patients 15 had an obstructed outflow pattern with a full bladder, which was relieved at a bladder volume of less than 390 ml (median 300, range 250 to 600). Only 2 of these 15 patients had a normal vesical end filling pressure of less than 20 cm H2O. There was no obstruction in 9 patients, of whom 5 had increased vesical end filling pressures. Followup in patients who had normal tracer outflow on a full bladder showed no decrease in renal function, while a small decrease was seen in patients who had obstructed outflow on a full bladder. CONCLUSION: This novel, full bladder 99mtechnetium-mercaptoacetyltriglycine scintigraphic technique provides the ability to detect bladder volumes at which obstructive outflow patterns develop in patients with severe bladder dysfunction.

Report of laparoscopic ureteropyelostomy for symptomatic "yo-yo" reflux in an adult.

Symptomatic presentation of partial duplication of the ureter in adults is rare. However, there are reports of such conditions being treated with surgical correction with varying degrees of success. We present the case of a 23-year-old woman who underwent what is, to our knowledge, the first reported laparoscopic ureteropyelostomy for symptomatic "yo-yo" reflux.

Standing the test of time: long-term outcome of reconstruction of the exstrophy bladder.

The surgical management of classic bladder exstrophy has evolved over time. Different techniques are used to address the challenge of reconstructing these patients. We review the long-term outcomes of bladder exstrophy treatment from the published literature with regard to urinary continence, voiding and secondary complications. Continence now can be achieved in up to 80% of children in specialist centres. Whether such success can sustained into adult life is uncertain. About 40% of adults are dry in the best hands. Up to 84% of children can void, but there is some evidence that this function is lost with time in 70%. The need for bladder augmentation is widely variable between series, reported in 0-70% of children. This reduces the ability to void spontaneously to about 50% of children. It brings with it the later risk of metabolic disturbance and stone formation. Adults with exstrophy have a 694-fold increase in the risk of bladder cancer by the age of 40 years.

Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties.

Stones are a common complication of the storage of urine in intestinal reservoirs. Previous studies have identified predisposing physical characteristics in the reservoirs. Biochemical and dietary factors have been little investigated. Fifteen patients (6 males and 9 females) who had undergone various enterocystoplasty operations and who had subsequently formed either upper or lower urinary tract stones were investigated. The programme has been previously described and included stone, blood and urine analysis and dietary review. Comparison was made with 15 age- and sex-matched idiopathic stone formers with normal bladders. Stones were infective in origin in 86% of cases, and 14% were sterile. Metabolic screen showed that 80% of enterocystoplasty patients had risk factors for at least three different types of stone. All patients had raised pH (mean 6.93) and hypocitraturia. Five had a raised alkaline phosphatase. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria were found in 33% of patients. Five had a 24-h urine volume below 1.6 l/day. All patients had a high risk index (PSF) for phosphatic stones and 12 also for calcium oxalate stones. Compared to age-and sex-matched idiopathic stone-formers, the urine had a higher pH, sodium and protein excretion and a lower calcium and citrate excretion. Although the patients were already selected as stone-formers, the data show that metabolic and dietary factors are present. They may be as important in the aetiology of the stones, as the already recognised factors of infection and poor reservoir drainage. Investigation should include such factors, the presence of which may be taken into account in a prophylactic regime.

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Modified ureterosigmoidostomy (Mainz II): a long-term follow-up.

OBJECTIVE: To assess the long-term results in patients treated using a modified ureterosigmoidostomy (Mainz II). PATIENTS AND METHODS: Between 1994 and 1999, 17 patients had their lower urinary tract reconstructed by a ureterosigmoidostomy, modified by reconfiguring the rectum to make a low-pressure reservoir (Mainz II). All patients were followed on a standard protocol. Data were extracted from the database and from a review of the case-notes. In 12 patients the procedure was with a radical cystectomy for carcinoma. Five had a failed conventional ureterosigmoidostomy for bladder exstrophy and therefore proceeded to a Mainz II. The data on continence and complications were retrieved for a retrospective analysis; the mean (range) follow-up was 6.4 (4-8.6) years. RESULTS: Ten of those with bladder cancer and one in the revision group were continent. Two patients in the revision group had sufficiently severe nocturnal incontinence to require conversion to a colonic conduit. Seven of the 17 patients had hyperchloraemic acidosis, one had pyelonephritis and one had renal stones. There were no anastomotic neoplasms. CONCLUSION: The Mainz II has a good outcome if used as the primary procedure. In patients with an existing ureterosigmoidostomy who are incontinent, detubularization of the rectosigmoid alone is unlikely to restore continence.

Long-term outcome of Fowler-Stephens orchiopexy in boys with prune-belly syndrome.

PURPOSE: Intra-abdominal testes in boys with prune-belly syndrome have been conventionally managed by 1 or 2-stage orchiopexy with division of the gonadal vessels. We reviewed a series of adults with prune-belly syndrome to assess the morphological and functional outcome of orchiopexy in childhood with specific reference to the spontaneous onset of puberty, hormonal profiles and sexual function. MATERIALS AND METHODS: A total of 41 boys were divided into 3 groups depending on the type of orchiopexy performed, namely group 1-20 with bilateral 1-stage orchiopexy, group 2-10 with unilateral 1-stage and contralateral 2-stage orchiopexy, and group 3-11 with bilateral 2-stage orchiopexy. RESULTS: In group 1 9 of 20 patients had good scrotal testes bilaterally, 6 had a good scrotal testis on 1 side and 3 had small testes on each side. Two boys required testosterone supplementation but 18 had normal hormonal and sexual function. In group 2 6 of 10 patients had good scrotal testes bilaterally and 4 had a good scrotal testis on 1 side. All patients underwent spontaneous puberty with good sexual function. In group 3 7 of 11 boys had good scrotal testes bilaterally and 3 had 1 good testis with normal puberty and sexual function. These 10 patients underwent spontaneous puberty with good sexual function. CONCLUSIONS: The majority of boys with prune-belly syndrome had a satisfactory outcome after orchiopexy with division of the gonadal vessels with testicular function sufficient to induce puberty and maintain satisfactory sexual function in adult life.