Partial nephrectomy and autotransplantation with pyelovesicostomy for renal urothelial carcinoma in solitary kidneys: a clinical update.

OBJECTIVE: To evaluate the indications and outcomes after partial nephrectomy and renal autotransplantation for urothelial cancer in solitary kidneys, with special attention to the ease of endoscopic tumour control after pyelovesicostomy. PATIENTS AND METHODS: In all, 978 records of three institutions were reviewed for patients undergoing partial nephrectomy between January 1990 and December 2000. Ex vivo organ-preserving surgery was used in selected patients with a solitary kidney and localized pelvic or calyceal tumour. Autotransplantation was established using a pyelovesicostomy. The follow-up included ultrasonography, pelvi-cystoscopy, urine cytology, computed tomography, renal functional evaluation and video-urodynamics. The study included four patients aged 52-56 years, with a follow-up of 6-14 years. RESULTS: The histopathological status was pT1G2R0 in two and pT1G1R0 in the other two patients. One of them had an additional papilloma in the upper ureter. All patients entered a protocol of mitomycin/bacille Calmette-Guérin instillation therapy after surgery. The patients are currently alive with no recurrences. There is stable kidney function despite vesico-renal reflux, and normal bladder function with no subvesical obstruction. CONCLUSIONS: Partial nephrectomy and renal autotransplantation for renal urothelial cancer in solitary kidneys is feasible, but should only be used in the rarest cases, and for the most selective indications. Dialysis and renal replacement can be avoided. Pyelovesicostomy allows effective chemotherapy instillation therapy, and easy and secure urothelial cancer control of the upper urinary tract.

Investigations of ascorbic acid interference in urine test strips.

Ascorbic acid at higher concentration in urine samples can lead to false negative results in a number of urine tests, with a potential risk of clinical findings being overlooked, particularly with glucose and hemoglobin. For this reason, the ascorbic acid status of urine samples should always be routinely known so as to establish what adjustment needs to be made. A much better approach, however, is to use a test which is by design largely resistant to ascorbic acid. We compared five very common 10-parameter urine test strips from different manufacturers. The results of this study show that of the strips tested, only the product Combur-Test from Roche Diagnostics is largely resistant to ascorbic acid interference. Even lowest - but clinically relevant - concentrations of erythrocytes (10/microL), hemoglobin (0.03 mg/dL), and glucose (50 mg/dL) were correctly detected with concentrations of up to 400 mg/L ascorbic acid. Higher analyte concentrations correctly reacted positive even in the presence of up to 1000 mg/L ascorbic acid.

Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm.

OBJECTIVES: Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) < 4 cm has been accepted as alternative to radical nephrectomy (RN). However, NSS for tumours > 4 cm is controversial. We present our experiences and long-term oncologic outcome of RCC > 4 cm treated with NSS in a retrospective single-institutional analysis of 69 patients. METHODS: Between 1975 and 2004, elective NSS was performed in 368 patients at our institution, including 69 patients with sporadic, nonmetastatic RCC > 4 cm. Overall and cancer-specific survivals were estimated using the Kaplan-Meier method. RESULTS: Complications were seen in nine patients (13.0%). After a mean follow-up of 6.2 yr (median, 5.8 yr) seven patients (10.1%) had died, none of them of tumour-related causes. Tumour recurrence was detected in four patients (5.8%). The 5-yr overall survival probability was 94.9%. The 10-yr and 15-yr overall survival rates were both 86.7%. Cancer-specific survival was 100% after 5, 10, and 15 yr. CONCLUSIONS: Selected patients with localized RCC even > 4 cm can be treated with elective NSS providing optimal long-term outcome. The surgeon's decision for organ-preserving surgery should depend on tumour localisation and technical feasibility rather than on tumour size.

Partial nephrectomy with perfusion cooling for imperative indications: a 24-year experience.

OBJECTIVE: To report our 24-year experience with open nephron-sparing surgery for renal tumours, using cold ischaemia achieved by renal artery perfusion, as partial nephrectomy for imperative indications is a surgical challenge. PATIENTS AND METHODS: From 1980 to 2004, open partial nephrectomy was performed in 717 patients; of these, 65 (9.1%) with a solitary kidney, synchronous bilateral tumours or renal failure in the opposite kidney (imperative indication) had surgery under cold ischaemia, achieved by continuous perfusion of Ringer's lactate at 4 degrees C through the renal artery, which was clamped and cannulated. The tumour was resected in a bloodless field, with biopsies taken from the tumour bed. Focusing on patients with an imperative indication and cold perfusion, we report our perfusion technique, and the ischaemia time, complication rate and cancer-specific survival rate of these patients. RESULTS: The mean (SD, range) operative duration was 132 (103, 91-252) min and ischaemia time 49 (37, 31-71) min. The most common complications were postoperative haemorrhage in 19%, urinary fistula in 8% and acute renal failure in 6% of patients. There were no specific complications related to the perfusion technique (renal artery stenosis, renal artery or vein thrombosis). The mean (SD, range) long-term follow-up of 95 (71, 4.3-231) months showed increased but constant creatinine values (95 micromol/L before, 182 micromol/L after surgery; P < 0.05) with no need for long-term dialysis. The tumour-specific survival rate was 94%, 76% and 76% after 1, 5 and 10 years, respectively. CONCLUSIONS: Partial nephrectomy under cold ischaemia remains reserved for selected patients with renal tumours with an imperative indication. The technique provides excellent intraoperative visibility in an absolutely bloodless field, allows surgery with no pressure of time, and makes ex vivo workbench surgery with autotransplantation unnecessary. Perfusion cooling allows good tumour-specific long-term results, with stable residual kidney function sufficient to prevent dialysis.

Prevalence of diabetes-associated autoantibodies in schoolchildren: the Karlsburg Type 1 Diabetes Risk Study.

This study attempts to assess the prevalence of diabetes-associated autoantibodies in a general population in the northeastern part of Germany, with emphasis on autoantibodies against glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and insulin (IAA) by radioassays >/= 98th percentile, and AAbs binding on pancreatic sections (ICA) by immunofluorescence >/= 10 Juvenile Diabetes Foundation units. From a total of 11,840 schoolchildren tested for all four AAbs, 821 (6.9%) children were positive for single AAbs, whereas 83 (0.7%) had multiple AAbs. If the primary screening were performed by testing GADA/IA-2A/IAA, 94% of probands with single AAbs and all with multiple AAbs would be identified. The combinations of GADA/IA-2A, GADA/IAA, and IA-2A/IAA would identify 97.6, 98.8, and 85.5% of probands with multiple AAbs, respectively. Thus, combined AAb screening in the general population identifies those probands at risk for diabetes.

Multiple and high-titer single autoantibodies in schoolchildren reflecting the genetic predisposition for type 1 diabetes.

The study aimed to compare the HLA specificities of AAb-positive healthy schoolchildren with those of patients with type 1 diabetes (T1D). HLA-DRB1 and DQB1 alleles were determined in 178 AAb-positive and 339 AAb-negative schoolchildren aged 6-17 years without first-degree relatives with T1D and in 274 patients with T1D. AAbs against glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by (125)I-antigen binding, and islet cell cytoplasmic antibodies (ICAs) immunohistochemically. Here, 82.6% (147/178) of AAb-positive schoolchildren had single AAbs and 17.4% (31/178) had multiple AAbs. In both groups, GADA occurred with highest and IAA with lowest frequency. In children with single AAbs at levels between the 99th and 99.9th percentile, frequencies of the diabetes-associated DRB1 (*03, *04) and DQB1 (*02, *0302) alleles and the protective DRB1 (*15) and DQB1 (*0602) alleles did not differ from those of controls. In patients, the positive associations were confirmed for DRB1*04 (OR = 5.39) and DQB1*0302 (OR = 9.05), whereas DRB1*15 (OR = 0.05) and DQB1*0602 (OR = 0.06) were negative-associated (p < 0.001). The same association was found in schoolchildren with multiple AAbs for DRB1*04 (OR = 3.84), DQB1*0302 (OR = 4.95), and DRB1*15 (OR = 0.1; p < 0.001-0.014), and with high-titer single AAbs (>/=99.9th percentile), but none of them had DQB1*0602. The highest risk genotype DQB1*02/*0302 occurred in 36.5% of patients (OR = 21.07) and in 19.3% of children with multiple AAbs (OR = 8.8; p<0.001). It is concluded that probands with multiple and high-titer single AAbs in the general population have the same genetic predisposition for T1D as patients and are therefore at highest risk for the disease.

Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs.

Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221-442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C (84%) (P < 0.0001), 221-442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The competition pattern in type 1 diabetic patients differed from that in GAD65Ab-positive late autoimmune diabetes in adults (LADA) patients (n = 44), first-degree relatives (n = 38), and healthy individuals (n = 14). Whereas 87 and 72% of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively, only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and 28% of healthy individuals showed competition (P < 0.0001). These findings support the view that type 1 diabetes is associated with disease- and epitope-specific GAD65Abs and supports the notion that the middle epitope is disease associated. These GAD65-specific rFabs should prove useful in predicting type 1 diabetes and in the study of conformational GAD65Ab epitopes.

The Karlsburg type 1 diabetes risk study of a normal schoolchild population: association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles in antibody-positive individuals.

The intent of this study was to analyze the prevalence of diabetes-associated autoantibodies (AAbs) at or above the 99(th) percentile as well as their association with human leukocyte antigen (HLA)-DQB1 alleles in a normal population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by (125)I-antigen binding and islet cell antibodies (ICA) immunohistochemically in 181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P < 0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001-0.006) as well as a decreased frequency in the protective allele *0602 (P < 0.001-0.022). DQB1*0602 was completely absent within children with multiple AAbs or with GADA, IA2-A, or IAA at or above the 99.9(th) percentile. In comparison to children with single AAbs, the frequency of associated/protective alleles of children with multiple AAbs was enhanced/diminished (P = 0.004-0.009). The study shows that also in the general population the multiple AAbs or high level single AAbs predict rather certainly a HLA-DQB1-mediated diabetes susceptibility as shown for first degree relatives of type 1 diabetic patients.

Th2 dominance of T helper cell response to preproinsulin in individuals with preclinical type 1 diabetes.

In human type 1 diabetes (T1D) autoantibodies to insulin precede clinical disease, while little is known about the contribution of insulin-specific T lymphocytes-in particular, T helper (Th) subsets. Here we have studied the in vivo primed cytokine response to preproinsulin in peripheral blood mononuclear cells (PBMCs) and two major Th cell subsets-CD45RO+ memory cells and CD45RA+ naive/resting cells-in 35 individuals with HLA-DRB1*04, DQB1*0302 diabetes risk marker: 12 patients with T1D, 12 autoantibody-positive (Ab+) individuals, and 11 healthy controls. Cytokine secretion (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. In Ab+ individuals our results reveal higher IL-4 levels in CD45RO+ memory cells and higher IL-5 levels in CD45RA+ naive/resting cells, while higher IL-2 production was found in PBMCs. In contrast, in PBMCs of T1D patients higher IFN-gamma and IL-10 secretion was found. Our data delineate characteristic cytokine patterns in peripheral T lymphocytes from patients at different stages of the T1D development.