Robert J Irwin

Accuracy of diagnosis by guided biopsy of renal mass lesions classified indeterminate by imaging studies

OBJECTIVESnTo define the accuracy, safety, and impact of percutaneous biopsies of indeterminate mass lesions as an additional diagnostic tool. The vast majority of renal mass lesions are routinely diagnosed by radiographic features alone. However, with the increased use of computed tomography scanning and ultrasound, many smaller renal masses, which are indeterminate (refractory to categorization on the basis of imaging alone), are now being discovered.nnnMETHODSnWe retrospectively reviewed 583 patients (364 male and 219 female) with indeterminate renal mass lesions diagnosed by imaging studies that were further investigated by percutaneous biopsy. Patients were followed up for at least 5 years if the biopsy result demonstrated a benign lesion, or they underwent surgical exploration if the biopsy result demonstrated a malignancy. Biopsy or aspiration material was assessed by histopathologic and cytologic evaluation and, when appropriate, with biochemistry, Gram stain, culture, and sensitivity. The biopsy site was localized by computed tomography, ultrasound, or fluoroscopy.nnnRESULTSnFive hundred eighty-three patients with indeterminate renal mass lesions (representing 7.2% of all renal masses diagnosed from 1967 through 1996) were diagnosed by imaging studies complemented by guided biopsy. Sixty-six patients were lost to follow-up, leaving 517 patients who were analyzed. In 393 cases (76%), the imaging-guided biopsy provided a definitive diagnosis. The incidence of false diagnoses was 1.2% (7 biopsies). In 124 of the cases (21%), imaging-guided biopsy was unable to determine the etiology of the lesion with acceptable confidence; of these, 21 biopsies did not provide enough material to establish the diagnosis (16.9%).nnnCONCLUSIONSnOverall, percutaneous biopsy of the kidney has proved to be a safe and accurate diagnostic procedure, with impact on the management of cystic or solid renal lesions.

Endourologic management of benign ureteral strictures with and without compromised vascular supply.

OBJECTIVESnTo retrospectively assess the efficacy of balloon dilation, endopyelotomy/ureterotomy, and stenting alone in the management of benign ureteral strictures with intact or compromised vascular supply.nnnMETHODSnOne hundred fourteen patients with benign ureteral strictures were assessed after at least a 2-year follow-up (range 2 to 16 years, mean 6.3). Balloon dilation was performed in 81, endopyelotomy/ureterotomy with temporary stenting in 27, and ureteral stenting alone in 6 patients. Ureteral strictures were divided into strictures with intact or with compromised vascular supply.nnnRESULTSnBalloon dilation was successful in short ureteral strictures with intact vascular supply in 33 of 37 (89.2%), but only in 3 of 8 (37.5%) long ureteral strictures and in 1 of 2 (50%) recurrent ureteropelvic junction strictures. Balloon dilation was less successful when the vascular supply was compromised in 2 (40%) of 5 short strictures, 1 (16.7%) of 6 long strictures, and 2 (33.3%) of 6 recurrent ureteropelvic junction strictures. Endopyelotomy/ureterotomy was successful in 17 (89.5%) of 19 strictures with compromised vascular supply.nnnCONCLUSIONSnBalloon dilation is recommended for management of short strictures with intact vascular supply. Endoureterotomy with stenting is recommended for all long ureteral strictures, for ureteropelvic junction stenoses, and for short ureteral strictures with compromised vascular supply and benign underlying etiology.

Percutaneous nephrostomy as adjunct management in advanced upper urinary tract infection

OBJECTIVESnTo determine by retrospective review of 315 percutaneous nephrostomies, performed for pyonephrosis, whether this intervention has major clinical advantages.nnnMETHODSnFrom 1977 to 1996, under the direct supervision of the senior author of this report (E.K.L.), at seven hospital sites, 315 patients (181 males, 134 females; 17 to 88 years of age) were treated with percutaneous nephrostomy and antibiotic therapy for infected hydronephrosis.nnnRESULTSnAdditional or disparate pathogens were identified in 116 (36.8%) of 315 patients, leading to a clinically significant change in, or addition of, antibiotics and/or antifungal agents in 84 (73%) of 116. Most notably, we often found a clinically important disparity between the results of cultures obtained from the nephrostomy and those obtained from bladder-urine specimens.nnnCONCLUSIONSnThis retrospective review confirms previously reported advantages of percutaneous upper urinary tract drainage as a potentially life-saving adjunct in the treatment of pyonephrosis. Several case studies highlight the advantage of this maneuver in difficult cases involving obstruction due to extensive fungus or debris. In particular, our review focuses attention on the clinically important insight that urine cultures from percutaneous nephrostomy drainage often identify pathogens that differ from those detected in concurrent bladder cultures.

IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells

BackgroundSTAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic.MethodsWe looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells.ResultsAlthough both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells.ConclusionsWe conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed.

Retinoid and androgen regulation of cell growth, epidermal growth factor and retinoic acid receptors in normal and carcinoma rat prostate cells

Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR alpha mRNA was elevated whereas the levels of RAR gamma and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR alpha and gamma mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 microM RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines.

Androgen and retinoic acid interaction in LNCaP cells, effects on cell proliferation and expression of retinoic acid receptors and epidermal growth factor receptor

BackgroundModulation of the expression of retinoic acid receptors (RAR) α and γ in adult rat prostate by testosterone (T) suggests that RAR signaling events might mediate some of the androgen effects on prostate cells.MethodIn this study, we examined the interactions between T and retinoic acid (RA) in cell growth of human prostate carcinoma cells, LNCaP, and their relationship with the expression of RAR and epidermal growth factor receptor (EGF-R).ResultsBoth T and RA, when administered alone, stimulated 3H-thymidine incorporation in LNCaP cells in a dose-dependent manner; the effect of each agent was reciprocally attenuated by the other agent. Testosterone treatment of LNCaP cells also resulted in dose dependent, biphasic increases in RAR α and γ mRNAs; increases paralleled that of 3H-thymidine incorporation and were attenuated by the presence of 100 nM RA. These results suggest a link between RAR signaling and the effect of T on LNCaP cell growth. Gel electrophoretic mobility shift assays revealed the presence of putative androgen responsive element (ARE) in the promoter region of RAR α gene, suggesting that a direct AR-DNA interaction might mediate the effects of T on RAR α gene. Furthermore, treatment of LNCaP cells with 20 nM T resulted in an increase in EGF-R. In contrast, EGF-R was suppressed by 100 nM RA that also suppressed the effect of T.ConclusionsCurrent results demonstrate interactions between T and RA in the expression of RARs and cell growth in LNCaP cells. The presence of putative ARE in the promoter of the RAR α gene suggests that AR-DNA interaction might mediate the effects of T on RAR α gene. The opposite effects of T and RA on the expression of RAR and EGF-R suggest that signal events of these receptors might be involved in the interaction between T and RA in the control of LNCaP cell growth.

“Indeterminate” cystic lesion of the kidney partially lined by small cells with clear cytoplasm—malignant or benign?

Complex renal cysts, which present radiographically as indeterminate for malignancy (Bosniak category III), can prove challenging both pathologically and clinically. We report a case of a renal cyst that, by standard radiographic and histologic criteria, should have been diagnosed as a malignant cystic renal cell carcinoma. However, the cytogenetic profile appeared more closely consistent with cystic renal adenoma or low-grade papillary renal cell carcinoma--tumors with limited metastatic potential. We postulate that other, similarly complex, renal cysts might also be more precisely defined by meticulous histopathologic examination, supported by cytogenetic study.