Manifestations of Von Hippel Lindau syndrome: a retrospective national review.

INTRODUCTION: Von Hippel Lindau (VHL) disease is a syndrome that is defined by variety of tumours such as cerebellar haemangioblastomas, renal cell carcinomas, phaeochromocytomas, pancreatic adenomas and ear, nose and throat (ENT) adenomas. This disease is often genetic and inherited in an autosomal dominant fashion, and can present in childhood, adolescence or adult life. This study describes the presentation, natural history and manifestations of patients attending our institutions with this condition. We aim to highlight the importance of screening in diagnosing the manifestations of VHL. METHODS: A retrospective review was performed on all patients diagnosed with VHL and coded as such by the national Hospital Inpatient Enquiry Scheme at Beaumont Hospital Dublin and Cork University Hospital. This was performed over a 20 years period between 1989 and 2009. Age, sex, mode of presentation, presence or absence of end stage kidney disease and genotype were documented. Presence or absence of the characteristic tumours of VHL was also recorded, as were the initial presenting features of these tumours. RESULTS: Thirty-six patients were diagnosed with VHL. These patients ranged from 18 to 78 years old. Three patients were members of the Irish travelling community. The most frequent mode of presentation was altered neurological signs (40%), with a significant proportion presenting with haematuria (23%). Patients diagnosed prior to 1995 were more likely to have presented with significant complications of VHL, while those diagnosed after this time were more likely to have been diagnosed via screening. Genetic testing was performed on 17 patients; those who did not have genetic testing performed were more likely to have been diagnosed prior to the era of genetic testing. Thirty-one patients had received screening for complications of VHL including renal cell carcinomas, central nervous system (CNS) haemangioblastomas and phaeochromocytomas. The patients who did not receive any screening presented with neurological symptoms. CONCLUSION: Beaumont Hospital Dublin and Cork University Hospital are tertiary referral centres for nephrology, urology and neurosurgery and deals with a significant proportion of patients diagnosed with VHL in Ireland. This study highlights the significant burden of this illness and emphasizes the importance of screening for these renal/CNS and ENT complications. This study also highlights the importance of family screening in diagnosing this condition.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

BACKGROUND: Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms. METHODS: We report a case of a 67-year-old Caucasian woman, who was admitted with history of bleeding per rectum. We conducted a literature review of metachronous and synchronous multiple primary neoplasms. RESULTS: Colonoscopy revealed a 3 cm tumour in the caecum and a small sigmoid tubulovillous polyp. Staging computed tomography showed a non-enhancing mass in the upper pole of the right kidney. Following a radical nephrectomy/right hemicolectomy, microscopy demonstrated a renal cell carcinoma. Follow-up colonoscopy visualised a mucosal irregularity at the site of the previous sigmoid polyp, with biopsies confirming invasive adenocarcinoma. Patient underwent a total colectomy with an ileo-rectal anastamosis. CONCLUSION: Multiple primary neoplasms are a well-recognised clinical entity. This report emphasises the need for a comprehensive evidence-based work-up in all cancer cases, especially when dealing with renal cell carcinoma, to look for coexisting metachronous/synchronous primary neoplasms.

An unusual case of cancer of the urachal remnant following repair of bladder exstrophy.

INTRODUCTION: We report the first case of cancer of the urachal remnant following repair of bladder exstrophy, in a renal transplant recipient. METHOD: A retrospective review of this clinical case and the associated literature were performed. CONCLUSION: This unusual case highlights two very rare entities. Bladder exstrophy has an incidence of 1 in 50,000 newborns, whereas urachal cancer accounts for less than 1% of all bladder tumours.

Is mechanical bowel preparation necessary in patients undergoing cystectomy and urinary diversion?

OBJECTIVE: To compare the surgical outcome in patients with or with no bowel preparation before cystectomy and ileal conduit urinary diversion, specifically assessing local and systemic complications. PATIENTS AND METHODS: All patients undergoing cystectomy and ileal conduit urinary diversion between January 1991 and December 1999 were assessed retrospectively. Twenty-two receive no bowel preparation (group 1) and were compared with 64 who had (group 2). Patients had similar demographic characteristics, stage and grade of tumour. Patients in group 2 received a standard 4-day bowel preparation and group 1 received no lavage or enemas. All patients underwent a standard iliac and obturator lymph node dissection, and cystoprostatectomy or anterior exenteration and ileal conduit urinary diversion. All patients received intraoperative metronidazole and gentamicin intravenously, and two further doses after surgery. RESULTS: Deaths after surgery were comparable in the two groups (two in group 1 and four in group 2) and the incidence of wound infection was similar (three and seven, respectively). There were no significant differences between the respective groups for fistula and anastomotic dehiscence (two and six) or sepsis (three and six). Group 2 had a higher incidence of wound dehiscence (one) than in group 1 (none). The incidence of prolonged postoperative ileus was lower in group 1 (one vs 12), as was the length of hospital stay (31.6 days vs 22.8 days). CONCLUSIONS: Bowel preparation had no advantage for the surgical outcome but it increased the length of hospital stay.

Primary lymphoma of the bladder: a report of three cases.

BACKGROUND: Primary lymphoma of the bladder is rare and its management is an evolving field. AIMS: To highlight primary lymphoma of the bladder as a possible diagnosis in cases of bladder neoplasm and to illustrate the currently favoured management options. METHODS: Three cases of primary bladder lymphoma are reported and management is reviewed. RESULTS: Each of the three cases was managed differently with each management approach yielding a favourable outcome. CONCLUSION: Chemotherapy combined, if necessary, with surgery or radiation therapy, should be the standard of care, depending on the full histological diagnosis.

Clinical and histological assessment of collagen-induced arthritis progression in the diabetes-resistant BB/Wor rat.

Collagen-induced arthritis in the diabetes-resistant BB (DR BB)/Wor rat is a severe, aggressive disease initiated by immunization with heterologous native Type II collagen. Onset of clinical symptoms reproducibly occurs in 100% of animals between days 10 and 12 following collagen immunization. Hypertrophy of the synovial lining is the first histological manifestation of the early inflammatory arthritis. A mild inflammatory infiltrate in the synovium rapidly becomes a fibrovascular pannus eroding articular cartilage and subchondral bone. Beginning at the joint margins, an active synovitis is present. Light microscopy and immunohistochemical staining show the infiltrate to be comprised of mononuclear (lymphocytes, macrophages) and polymorphonuclear inflammatory cells. In addition, there is histological evidence for chronic inflammatory nodules and necrotizing vasculitis in connective tissue from diseased joints, both morphologic features associated with rheumatoid arthritis in humans. Subchondral bone erosion appears to be mediated largely by the resorptive action of activated osteoclasts. These histological parameters of disease progression in the DR BB/Wor rat are similar to human rheumatoid arthritis. The extensive degree of similarity in the pathology of DR BB/Wor rat collagen-induced arthritis and human rheumatoid arthritis supports the role of this model as an in vivo disease model for human rheumatoid arthritis.

Experimental evaluation of expanded polytetrafluoroethylene for reconstruction of orbital floor defects.

OBJECTIVE: This study evaluates the efficacy of a medical grade expanded polytetrafluoroethylene (e-PTFE) sheet for reconstruction of the orbital floor. MATERIALS AND METHODS: Orbital floor defects were created in 10 domestic sheep and reconstructed with the 1-mm thick e-PTFE sheet. The surgical sites were evaluated for the development of enophthalmos and biocompatibility at 2 weeks, and at 1-, 2-, 4-, and 6-months intervals. RESULTS: The results of this indicate that the e-PTFE material has excellent handling characteristics, provides stability to correct surgically created enophthalmos, and causes essentially no foreign body reaction. CONCLUSION: Expanded polytetrafluoroethylene proved to be an excellent alloplastic material for the repair of orbital floor defects in this experimental study.

Renal transplantation in patients with spina bifida.

OBJECTIVES: Renal transplantation in patients with spina bifida is not commonly performed, although these patients have a high incidence of end-stage renal disease. METHODS: Between February 1989 and December 1991, we performed 5 cadaveric renal transplants in 4 patients with spina bifida. There were 3 male patients and 1 female patient with a mean age of 22.5 years (range, 10 to 36 years). All patients had lumbar myelomeningoceles repaired shortly after birth. Three patients were wheelchair-bound due to their neurologic deficit. Prior to renal transplantation, management of neuropathic bladder dysfunction consisted of ileal conduit (1 patient), "clam" cystoplasty with clean intermittent self-catheterization (CISC; 1 patient), and CISC alone (2 patients). RESULTS: In this series, 1 patient died of fungal septicemia 6 weeks postoperatively. One patient underwent transplantation again following primary nonfunction of his original allograft. Serum creatinine levels were 56, 91, and 120 mmol/L, respectively, after 18 months' follow-up. CONCLUSIONS: This article demonstrates the feasibility of cadaveric renal transplantation in selected patients with end-stage renal failure and spina bifida. We currently recommend that these patients not be excluded from gaining the benefits of renal transplantation.

Maxillary and mandibular reconstruction using calvarial bone grafts and Branemark implants: a preliminary report.

A review of 24 patients reconstructed with calvarial bone grafts and 93 Branemark implants (Nobelpharma, Chicago, IL) revealed an overall success rate of 91.4%. Two grafting techniques were used. A vertical grafting technique with delayed implant placement had an 86% success rate in 13 patients who had 50 implants placed. The average follow-up for this group was 31 months. A horizontal grafting technique with immediate implant placement had a success rate of 98%. This group included 13 patients who had 43 implants placed at the time of their bone grafting procedure. Two patients had a combination of grafting techniques. The average follow-up for this group was 18 months. A patient questionnaire revealed a high percentage and degree of satisfaction.

Transplant nephrectomy over 20 years: factors involved in associated morbidity and mortality.

Of 1,048 renal transplants performed between 1971 and 1990, transplant nephrectomy was performed in 86 (8.2%). Mean patient age was 33 years (range 3.8 to 66.5). Postoperative complications occurred in 60% of the patients, including wound infection in 20% and major hemorrhage in 4 patients. The external iliac artery was ligated in 4 patients. The incidence and severity of the complications were greater in patients with acute rejection. Four patients died: 1 of ischemic bowel and metastatic carcinoma, 1 of pulmonary embolism, and 2 of sepsis and disseminated intravascular coagulation. The nephrectomy rate increased significantly (p < 0.005) when cyclosporine A was initially introduced. Added care is necessary when new immunosuppressants are used. The majority of our failed transplants were left in situ without compromising overall patient well-being.

c-myc expression in renal carcinoma: correlation with clinical parameters.

There is evidence that c-myc is expressed in renal carcinomas and that it is associated with histological grade. This study reports on the clinical correlations of oncogene expression and clinical features of the disease. Tissue sections from 97 patients (95 primary and 12 secondary cancers) were immunostained with a c-myc oncoprotein antibody. The tumours were scored for extent and intensity of nuclear and cytoplasmic staining. Ninety patients were suitable for follow-up study. High levels of expression correlated significantly with increasing T category and nuclear grade, as well as with venous invasion. No correlation with nodal involvement, the presence of metastases, tumour architecture or cell type was found. The extent of nuclear staining was related to survival (although not to recurrence), but in a multivariate analysis did not provide independent prognostic information. It was concluded that semiquantitative assessment of levels of c-myc oncoprotein does not provide clinically useful prognostic information.

Autologous calvarial and iliac onlay bone grafts in miniature swine.

Calvarial bone has been reported to be superior to iliac bone for onlay bone grafting due to decreased resorption. This study evaluated the physical, histologic, and radiographic characteristics of calvarial and corticocancellous iliac onlay bone grafts in nine Pitman-Moore miniature swine at 2 weeks, and at 1-, 2-, 4-, 6-, 7-, 8-, 10-, and 12-month intervals. Compared with iliac grafts, the calvarial onlay grafts had more than a twofold greater radiographic density. Statistical analysis of the mature grafts using the standard of estimated means of the bone graft volumes revealed 85% retention of the calvarial grafts compared with 34% retention of the grafted iliac bone. There was no subjective difference in the rate or degree of revascularization between the two grafted materials.

Combined transmandibular-zygomatic approach and infratemporal craniotomy for intracranial skull base tumors.

Large intracranial skull base tumors remain surgically treacherous lesions. The preauricular transzygomatic infratemporal approach to this area has rapidly gained popularity. This article presents modifications to this approach which improved visualization and access to the infratemporal fossa. The procedure increases visualization, minimizes brain retraction, and results in improved resection and outcome. Reconstruction is rapid and there are minimal functional and cosmetic deficits.

Older donors and kidney transplantation.

Reluctance to use kidneys from older donors (> 50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation.

Ploidy and prognosis in renal carcinoma.

The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable.

A screening procedure for the intracellular expression of native proteins by Saccharomyces cerevisiae: discrimination of diphtheria toxin-resistant mutants.

A general method is described for screening Saccharomyces cerevisiae colonies for the intracellular expression of native proteins. Colonies are replicated onto nitrocellulose membranes and yeast cell walls are removed enzymatically. The resulting spheroplasts are rapidly lysed by placing chromatography paper soaked in hypotonic buffer on the membranes. Intracellular proteins released by spheroplast lysis are bound in situ to the nitrocellulose under non-denaturing conditions and potentially can be examined using enzymatic or immunologic methods. For example, in the present study colonies were screened for the presence of elongation factor 2 (EF-2) that can be [32P]ADP-ribosylated by diphtheria toxin and [32P]NAD+. Recognition by the toxin requires the presence in EF-2 of the unique post-translationally modified histidine derivative, diphthamide. The procedure described here reliably discriminates between wild-type yeast colonies and mutant colonies that do not synthesize diphthamide. In addition to facilitating the study of diphthamide biosynthesis in yeast, the more general application of this procedure will enable the screening of colonies with assays that require native proteins.

Artificial bladder replacement: a new design concept [see comment].

An effectively functioning artificial bladder would be useful after cystectomy because of the ease of insertion and the availability to all patients. In this report, we describe a new design concept based on negative pressure drainage of the kidneys and active voiding, and we present the results of testing this device. Although previous prosthetic bladders have had difficulties with renal failure from hydronephrosis, infection from retention of urine, and encrustation of the luminal surface, the current artificial complete bladder system addresses these problems.