Patterns of renal disease: A 30-year renal biopsy study at Chris Hani Baragwanath Academic Hospital, Soweto, Johannesburg, South Africa.

BACKGROUND: Data on renal pathology from sub-Saharan Africa are limited. OBJECTIVES: To report on biopsy-confirmed renal pathology over 30 years in Soweto, South Africa (SA). METHODS: Retrospective analysis was conducted of 1 848 adult native renal biopsies performed at Chris Hani Baragwanath Academic Hospital between 1 January 1982 and 31 December 2011. RESULTS: There was an even gender distribution, and 96.4% of patients were of black ethnicity. The mean (standard deviation) age of patients was 33.5 (12.6) years. The main clinical indications for renal biopsy were nephrotic syndrome (47.7%), acute kidney injury (19.8%) and asymptomatic urine abnormalities (8.1%). Secondary glomerular diseases (SGNs) (49.3%) occurred more frequently than primary glomerular diseases (PGNs) (39.7%). SGNs increased during the study period, while PGNs decreased (p<0.001). The most frequent PGNs were focal segmental glomerulosclerosis (FSGS) (29.6%), membranous glomerulonephritis (25.7%) and membranoproliferative glomerulonephritis (18.1%). Lupus nephritis (LN) (31.0%) was the most frequent SGN, followed by HIV-associated nephropathy (HIVAN) (13.3%) and malignant hypertension (12.5%). HIV-positive biopsies constituted 19.7% of all biopsies, and the proportion increased over time. In HIV-positive patients, the most common diagnoses were HIVAN (32.7%), HIV immune complex disease (11.8%) and FSGS (11.3%). CONCLUSIONS: This study contributes to our knowledge of renal pathology in SA and shows some data that differ from studies in other regions. The increase in SGNs probably reflects the influence of HIV and LN in the study population.

A round-robin gamma stereotactic radiosurgery dosimetry interinstitution comparison of calibration protocols.

PURPOSE: Absorbed dose calibration for gamma stereotactic radiosurgery is challenging due to the unique geometric conditions, dosimetry characteristics, and nonstandard field size of these devices. Members of the American Association of Physicists in Medicine (AAPM) Task Group 178 on Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance have participated in a round-robin exchange of calibrated measurement instrumentation and phantoms exploring two approved and two proposed calibration protocols or formalisms on ten gamma radiosurgery units. The objectives of this study were to benchmark and compare new formalisms to existing calibration methods, while maintaining traceability to U.S. primary dosimetry calibration laboratory standards. METHODS: Nine institutions made measurements using ten gamma stereotactic radiosurgery units in three different 160 mm diameter spherical phantoms [acrylonitrile butadiene styrene (ABS) plastic, Solid Water, and liquid water] and in air using a positioning jig. Two calibrated miniature ionization chambers and one calibrated electrometer were circulated for all measurements. Reference dose-rates at the phantom center were determined using the well-established AAPM TG-21 or TG-51 dose calibration protocols and using two proposed dose calibration protocols/formalisms: an in-air protocol and a formalism proposed by the International Atomic Energy Agency (IAEA) working group for small and nonstandard radiation fields. Each institution's results were normalized to the dose-rate determined at that institution using the TG-21 protocol in the ABS phantom. RESULTS: Percentages of dose-rates within 1.5% of the reference dose-rate (TG-21+ABS phantom) for the eight chamber-protocol-phantom combinations were the following: 88% for TG-21, 70% for TG-51, 93% for the new IAEA nonstandard-field formalism, and 65% for the new in-air protocol. Averages and standard deviations for dose-rates over all measurements relative to the TG-21+ABS dose-rate were 0.999±0.009 (TG-21), 0.991±0.013 (TG-51), 1.000±0.009 (IAEA), and 1.009±0.012 (in-air). There were no statistically significant differences (i.e., p>0.05) between the two ionization chambers for the TG-21 protocol applied to all dosimetry phantoms. The mean results using the TG-51 protocol were notably lower than those for the other dosimetry protocols, with a standard deviation 2-3 times larger. The in-air protocol was not statistically different from TG-21 for the A16 chamber in the liquid water or ABS phantoms (p=0.300 and p=0.135) but was statistically different from TG-21 for the PTW chamber in all phantoms (p=0.006 for Solid Water, 0.014 for liquid water, and 0.020 for ABS). Results of IAEA formalism were statistically different from TG-21 results only for the combination of the A16 chamber with the liquid water phantom (p=0.017). In the latter case, dose-rates measured with the two protocols differed by only 0.4%. For other phantom-ionization-chamber combinations, the new IAEA formalism was not statistically different from TG-21. CONCLUSIONS: Although further investigation is needed to validate the new protocols for other ionization chambers, these results can serve as a reference to quantitatively compare different calibration protocols and ionization chambers if a particular method is chosen by a professional society to serve as a standardized calibration protocol.

Prognostic factors for stereotactic radiosurgery-treated patients with cerebral metastasis: implications on randomised control trial design and inter-institutional collaboration.

INTRODUCTION: Defining key prognostic factors for patients with cerebral metastases who underwent stereotactic radiosurgery (SRS) treatment will greatly facilitate future clinical trial designs. METHODS: We adopted a two-phase study design where results from one cohort were validated in a second independent cohort. The exploratory analysis reviewed the survival outcomes of 1017 consecutive patients (with 3610 metastases) who underwent Gamma radiosurgery at the University of California, San Diego (UCSD)/San Diego Gamma Knife Center (SDGKC). Multivariate analysis was performed to identify prognostic factors. Results were validated using data derived from 2519 consecutive patients (with 17,498 metastases) treated with SRS at the Katsuta Hospital. RESULTS: For the SDGKC cohort, the median overall survival of patients following SRS was 7 months. Two year follow-up data were available for 85% of the patients. Multivariate analysis found that patient age, Karnofsky Performance Status, systemic cancer status, tumour histology, number of metastasis and cumulative tumour volume independently associated with overall survival (p<0.001). All statistical associations were validated by multivariate analysis of data derived from the Katsuta Hospital cohort. CONCLUSIONS: This is the first integrated study that defined prognostic factors for SRS-treated patients with cerebral metastases using an inter-institutional validation study design. The work establishes a model for collaborative interactions between large volume centers and provides prognostic variables that should be incorporated into future clinical trial design.

Chronic kidney disease in human immunodeficiency virus infection.

The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV-uninfected transplant recipients. However, high rates of acute and chronic rejection have been observed among HIV-infected kidney transplant recipients. The Infectious Diseases Society of America (IDSA) published guidelines in 2005, recommending that all individuals be assessed for kidney disease at the time of diagnosis of HIV infection with a screening urinalysis for proteinuria and a calculated estimate of renal function. Therefore any patient with persistent proteinuria, persistent haematuria or glomerular filtration rate < 60 mL/min per 1.73 m(2) should be referred to an institution where a specialist can evaluate this patient for further investigations. An integrated plan to reduce the progression to kidney failure together with lifestyle measures, focusing also on high risk groups with effective management at all levels of chronic kidney disease remains essential.

HIV-related nephropathy: a South African perspective.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of renal failure in those of African origin. A number of other kidney diseases occur in HIV-positive patients. We conducted a retrospective review of renal biopsies in HIV-positive Black African patients to determine the prevalence of both 'classic HIVAN' and non-HIVAN pathologies in this group. Clinical and laboratory data from HIV-positive patients who underwent renal biopsy from 1st January 2003 to 31st December 2004 were collected. Similar information on HIV-negative patients biopsied during the same period was also recorded by way of comparison to try and assess the influence of the virus on renal histologic patterns. HIV-positive group - 99 biopsies were suitable for study. The main histologic categories were 'classic HIVAN' (27%) and HIV immune complex kidney disease ('HIVICK') (21%). The subepithelial immune deposits in 'HIVICK' induced a newly described 'ball-in-cup' basement membrane reaction. Other glomerulonephritides included membranous, post-infectious disease, mesangial hyperplasia, and immunoglobulin A nephropathy. Overlapping clinical presentations prevented pre-biopsy histologic predictions. HIV-negative group - There were no examples of collapsing focal segmental glomerulosclerosis or nonspecific immune complex disease, but increased numbers of minimal change and membranoproliferative disease. 'Classic HIVAN' accounted for less than a third of the nephropathies occurring in HIV-positive Black South Africans. 'HIVICK' is another important cause of chronic kidney disease in this group. Future research is needed into the earlier detection and treatment of these diseases, which have a high mortality in our context.

Glass rod detectors for small field, stereotactic radiosurgery dosimetric audit.

This paper demonstrates the feasibility of using glass rod detectors for quality assurance audit of radiosurgery units. Five radiosurgery units (3 Gamma Knife model C, 1 Gamma Knife model U and 1 Cyberknife) located in California participated in the study. At each center glass rod detectors were used to measure a number of dosimetric parameters including relative collimator output factor and absolute dose rate. The Gamma Knife data obtained is in excellent agreement with the commissioning data generated by the manufacturer for each unit and the Cyberknife data is in general agreement with the data published by other centers. In particular the output factor of the 4 mm Gamma Knife helmet factor, a subject of abundant debate, was measured in the range 0.863-0.872 with an accuracy of better than 1% across the four participating centers. It is hoped that this pilot study will facilitate a nationwide postal audit of stereotactic radiosurgery units.

Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Risk management in a community Gamma Knife unit.

OBJECTIVE: The records of the San Diego Gamma Knife Center were retrospectively reviewed for unprogrammed events as part of a risk management assessment. MATERIALS AND METHODS: Review was made of the physicist notes of the first 1,000 patients successfully treated at the center. This encompassed 1,020 stereotactic frame placement procedures, accompanied by Gamma Knife radiosurgery in 98.0% of intended cases. A total of 7,145 Gamma Knife shots were delivered to 1,509 lesions. RESULTS: Of the 43 unprogrammed events documented, 8 were patient related and 14 were related to lesion growth or location; these were considered unavoidable. Further, one event was related to dose administration, 5 to diagnosis, 15 to technique; these were considered potentially avoidable. This yielded an avoidable error rate of 2.1% per patient, 1.4% per lesion treated, and 0.29% per shot. It was clear that more avoidable errors occurred early in the center's operation, consistent with a learning curve. Review of individual physician's cases revealed none appeared more likely to have an avoidable event. CONCLUSIONS: Consistently high quality may be achieved at a community-based Gamma Knife center if sufficient multidisciplinary involvement is achieved.

Pulse cyclophosphamide for steroid-resistant focal segmental glomerulosclerosis.

We report the response of ten patients (6 male, 4 female) with steroid-resistant focal segmental glomerulosclerosis (FSGS) to treatment with intravenous pulse cyclophosphamide (IVCP) together with oral prednisone. All patients had been treated with 60 mg/m2 oral prednisone daily for 2 months upon initial presentation. IVCP was given monthly at a dose of 500 mg/m2 over 6 months. Oral prednisone was given concurrently at 60 mg/m2 daily for 2 months and then on alternate days for 4 months, followed by 30 mg/m2 on alternate days for 6 months. Prednisone was then tapered monthly by 10 mg and finally discontinued. Five patients failed to respond to steroids from the onset and were considered as primary steroid resistant. Two of these patients achieved sustained remission after IVCP, one patient showed a partial response, with loss of edema, normalization of serum albumin, and persistent proteinuria, while two patients showed no response to IVCP. The other five patients had achieved remission after 2 months of daily prednisone at 60 mg/m2 upon initial presentation, but had suffered from more than three relapses per year and had eventually become steroid resistant. They were considered secondary steroid resistant. All five patients achieved sustained remission after IVCP. None of our patients suffered from adverse effects of IVCP. We suggest IVCP as an adjunctive therapy for steroid-resistant FSGS, particularly for patients with secondary steroid resistance.

Physics of rotating gamma systems for stereotactic radiosurgery.

PURPOSE: The purpose of this study was to evaluate the characteristics of a new rotating gamma system for stereotactic radiosurgery by comparison with a well accepted system. METHODS AND MATERIALS: A novel gamma unit for stereotactic radiosurgery has been developed and distributed to 15 hospitals in China. The unit contains 30 cobalt-60 gamma radiation sources with initial activity of 200 Ci (7.4 x 10(12) Bq) each. The sources are positioned along 30 arcs, and rotate continuously as a group in an axis orthogonal to the patient's body. Measurements have been made on a representative unit installed in the Auhai Radiosurgery Center at the Beijing Navy General Hospital in the People's Republic of China. Ionization chambers calibrated by an American accredited dosimetry calibration laboratory were used for these measurements, as well as radiochromic film and thermoluminescent dosimeters. The unit tested utilizes collimators of nominal diameters of 4, 8, 14, and 18 mm. Radiochromic film samples from a Leksell Model U Gamma Knife were evaluated by the same laboratory and are presented for comparison. The treatment planning system was not evaluated. RESULTS: Radiation-absorbed dose rates and profiles measured for this unit are comparable to those previously measured with the same techniques for the Leksell Model U Gamma Knife units in San Diego and Atlanta. CONCLUSION: This unit is capable of producing well collimated beams of high energy photons, suitable for stereotactic radiosurgery. It has similar physical characteristics to those previously reported for the Leksell Model U Gamma Knife unit.

Spindle epithelial tumour with thymus-like element (SETTLE): the predominantly monophasic variant.

AIMS: To describe two cases of spindle epithelial tumour with thymus-like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics. METHODS AND RESULTS: The thyroid masses were in a 4-year-old boy and a 25-year-old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin. CONCLUSION: We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.

Arteriovenous malformation animal model for radiosurgery: the rete mirabile.

PURPOSE: To study the effects of single-dose radiation on the porcine rete mirabile, a tangle of microvessels that mimics human arteriovenous malformations of the brain. METHODS: Eight retia mirabilia received a single dose of radiation under stereotactic location with digital angiography and CT. The following doses were applied: 20, 30, 40, 50, 60, 70, 80, and 90 Gy. The animals were followed up for a period of 7 months. Findings at neurologic examination, serial angiography, and histopathologic examination were analyzed. RESULTS: Progressive occlusion as observed by angiography corresponded to the histopathologic finding of intimal hyperplasia; that is, marked thickening of the vessel wall, progressing to occlusion of the vascular lumen, and associated thrombosis. A direct dose response was noted for these changes. Neurologic findings were related to the dose distribution and to histologic findings in structures adjacent to the rete mirabile. CONCLUSION: The rete mirabile is an excellent model by which to study the radiologic and histologic effects of single-dose radiation to the microvasculature of the central nervous system.

Radiosurgery for pineal tumors: is biopsy indicated?

Pineal region tumors can be difficult to biopsy, given the critical structures in the location of the pineal gland. Modern computerized imaging techniques like computed tomography and magnetic resonance imaging used in association with tumor markers and the age at presentation may enable treatment without biopsy using a rational treatment algorithm.

The open Gamma Knife Center concept.

A freestanding Gamma Knife radiosurgery center has been open for just over 1 year in La Jolla, Calif., USA, located in the grounds of a medium-sized community hospital. The center employs a full-time medical physicist and neurosurgical nurse together with clerical personnel. The neurosurgeons and radiation oncologists are drawn from the entire community and bill their fees separately. Written protocols for each indication to be treated govern patient eligibility and suggested treatment algorithms. Additionally, each patient to be treated is presented in conference, and a treatment strategy (i.e., radiosurgery, craniotomy, conventional radiation therapy) is decided. Twenty new physicians and physicists have begun training to use the Gamma Knife in the first year. Certification must be achieved before a clinician can be physician of record.

Hodgkin's disease following successful treatment of gastric teratoma in a neonatal female.

Teratomas of gastric origin are rare. We are aware of 90 such tumors having previously been reported, all of which have been benign and only three of which have arisen in females. We report a gastric teratoma that presented as an exophytic gastric tumor in an 8-week-old female, the fourth such recorded tumor in a female neonate. Complete surgical excision was followed by clinical and biochemical surveillance without adjuvant treatment. At 1 year the patient was well without evidence of residual or recurrent disease. The child developed Hodgkin's disease 3 years later, and we believe this to be the first recorded association of these two tumors.

The calibration and use of plane-parallel ionization chambers for dosimetry of electron beams: an extension of the 1983 AAPM protocol report of AAPM Radiation Therapy Committee Task Group No. 39.

This report is an extension of the 1983 AAPM protocol, popularly known as the TG-21 Protocol. It deals with the calibration of plane-parallel ionization chambers and their use in calibrating therapy electron beams. A hierarchy of methods is presented. The first is to calibrate the plane-parallel chamber in a high energy electron beam against a cylindrical chamber which has an Ncylgas value that has been obtained from a NIST traceable 60Co beam calibration. The second method, which is recommended for implementation by the ADCLs is an in-air calibration against a NIST-traceable calibrated cylindrical chamber in a Cobalt-60 beam to obtain a plane-parallel-chamber calibration factor in terms of exposure or air kerma. The third method places the two chambers in a phantom in a Cobalt-60 beam, and leads to an Nppgas value for the plane-parallel chamber. This report also gives Nppgas/NxAion)pp and Nppgas/(NkAion)pp values for five commonly used commercially available plane-parallel chambers: the Capintec PS-033, the Exradin P-11, the Holt, the NACP and the PTW-Markus. The calculation of these Ngas ratios introduces a Kcomp factor which is also calculated for the five parallel plate chambers. The use of the plane-parallel chambers follows the 1983 AAPM protocol for absorbed dose calibrations of electrons, except that new energy-dependent Prepl values are given for the Capintec PS-033 and PTW-Markus chambers consistent with the consensus of reports in the literature. For all the chambers, however, Prepl is unity for 20 MeV electrons. This report does not address the issue of the use of plane-parallel chambers in calibrating photon beams.