Amlesh Seth

Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g.

To compare the safety and efficacy of two alternatives for surgically treating symptomatic benign prostatic hyperplasia (BPH), i.e. transurethral vapour resection of the prostate (TUVRP) and holmium laser enucleation of the prostate (HOLEP), with transurethral resection of the prostate (TURP), the standard surgical therapy, as treating large prostates is associated with greater morbidity, and to date there is no simultaneous comparison of these three methods.

Severely encrusted polyurethane ureteral stents: Management and analysis of potential risk factors

OBJECTIVES To review the management of heavily encrusted and stuck JJ ureteral stents. We report our experience and review current published reports in managing heavily encrusted and stuck JJ stents, the guidelines for management, and the prevention of such problems. METHODS We reviewed our stent records from January 1994 to December 2000 and analyzed our stent complications and their final outcome. Fifteen patients had heavily encrusted and stuck stents. Of these, 14 were encountered in patients with a sizable stone burden (400 to 650 mm(2)) and 1 occurred in a patient with malignant ureteral obstruction. Sandwich combinations of multiple extracorporeal shock wave lithotripsy/traction and endourologic procedures were used to render them stone and stent free. The stent was examined and the encrustation was analyzed by x-ray crystallography. RESULTS Of 15 patients, 13 were available for evaluations; 1 patient was lost to follow-up and 1 patient died. The average stone burden was 625 mm(2). The encrustation was localized to the upper end in eight and to the lower and upper end in three. In 4 cases, the entire stent was encrusted, and the lumen was occluded in 12. All 13 patients with stuck, fragmented, and encrusted stents were rendered stone and stent free; 2 of the 13 had clinically insignificant residual stones (less than 2 mm). Calcium phosphate and monohydrate stones were the most commonly encountered stone encrustations. CONCLUSIONS Stent encrustation is one of the most serious complications of polyurethane JJ stents. Multimodal endourology should form the cornerstone of therapy for heavily encrusted stuck stents. It is important to maintain an efficient computerized stent log under the direct supervision of a physician. Patients with probable risk factors should be monitored even more frequently to avoid mishaps and morbidity.

Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NFκB, TNF-α and caspase-3 expression in wistar rats.

Cisplatin is an effective chemotherapeutic agent that displays dose-limiting nephrotoxicity. In the present study the wistar rats were subjected to concurrent prophylactic oral treatment of rutin (75 and 150 mg/kgb.wt.) against the nephrotoxicity induced by intraperitoneal administration of cisplatin (7 mg/kgb.wt.). Efficacy of rutin against the nephrotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes and expression levels of molecular markers of inflammation and apoptosis. Rutin pretreatment prevented deteriorative effects induced by cisplatin through a protective mechanism that involved reduction of increased oxidative stress as well as caspase-3, TNF-α and NFκB protein expression levels. We found that the beneficial effect of rutin pretreatment is mediated partially by its inhibitory effect on NFκB and TNF-α pathway mediated inflammation, caspase-3 mediated-tubular cell apoptosis, as well as by restoration of histopathological changes against cisplatin administration.

Post-ESWL, clinically insignificant residual stones: reality or myth?

OBJECTIVES To assess the significance of asymptomatic residual stone fragments of less than 4 mm (clinically insignificant residual fragments [CIRFs]) after extracorporeal shock wave lithotripsy (ESWL). METHODS Eighty-one patients were followed up for 6 to 60 months (mean 15) after ESWL to determine the fate of the CIRFs. RESULTS Of the 81 patients, 6 were lost to follow-up, leaving 75 patients. During follow-up, fragments passed spontaneously in 18 patients, remained stable in 13 patients, and became clinically significant in 44 patients who developed one or more complications. For the latter patients, repeated ESWL was done in 16, percutaneous nephrolithotomy in 3, and ureteroscopic stone removal in 4 patients. The remaining 21 patients were treated conservatively with analgesics. We found that 53% of the CIRFs located in the pelvis passed spontaneously, and most of the CIRFs in caliceal location became clinically significant. Also, as the stone burden and number of stone fragments increased, the risk of CIRFs becoming clinically significant increased. The outcome was the same whether a metabolic abnormality was present or not, provided the patient received appropriate treatment. The clearance rate was highest in the first 6 months. Finally, as the duration of follow-up increased, the rate of complications increased. CONCLUSIONS Patients with residual stones after ESWL require close follow-up and timely adjuvant therapy. As the number and size of residual fragments increased, the risk of complications increased. A pelvic location was a favorable factor for spontaneous passage. Metabolic defects, if treated adequately, did not increase the regrowth rate. Although the complete clearance rate of CIRFs with repeated ESWL was lower than for the operative interventions, most patients improved with this modality.

Cutaneous Metastases in Renal Cell Carcinoma

Cutaneous metastasis from renal cell carcinoma is believed to be rare. We present our experience with 10 (3.3%) cases seen in the last 12 years among 306 cases of renal adenocarcinoma treated at our center. There were 9 males and 1 female. Age ranged from 30 to 65 years (average 45 years). 5 patients had skin metastases at the time of presentation (stage IV). In one of them the skin nodule, rather than urologic symptoms, was the presenting complaint. 5 patients presented with skin metastasis during follow-up after nephrectomy. The average time to skin metastasis was 51 months for patients in stage I and 13 months in stage IIIb. The scalp was the most common site of metastasis followed by chest and abdomen. 90% of patients had secondaries in at least one other site, most commonly in lungs (4 cases) and bones (5 cases). 4 patients were treated with interferon-α 6 MIU, subcutaneously, three times a week for varying periods from 3 to 4 months but there was no response. In conclusion, cutaneous secondaries from RCC, though uncommon, are not very rare. A few patients may present with a skin mass before detection of the renal tumor. Patients with low-stage disease at presentation may also develop cutaneous secondaries, therefore a prolonged follow-up is required. The commonest site for cutaneous metastasis from RCC is the scalp and face. Most patients had at least one other site of systemic metastasis, hence they were not candidates for curative therapy. Interferon therapy was not helpful. Mean survival after detection of cutaneous metastasis was 7 months.

Spectrum of stone composition : structural analysis of 1050 upper urinary tract calculi from northern India

Abstract Background:  The purpose of the present paper was to study the spectrum of stone composition of upper urinary tract calculi by X‐ray diffraction crystallography technique, in patients managed at All India Institute of Medical Sciences.

Hesperidin alleviates acetaminophen induced toxicity in wistar rats by abrogation of oxidative stress, apoptosis and inflammation

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The present study demonstrates the comparative hepatoprotective and nephroprotective activity of hesperidin (HD), a naturally occurring bioflavonoid against APAP induced toxicity. APAP induces hepatotoxicity and nephrotoxicity as was evident by abnormal deviation in the levels of antioxidant enzymes. Moreover, APAP induced renal damage by inducing apoptotic death and inflammation in renal tubular cells, manifested by an increase in the expression of caspase-3, caspase-9, NFkB, iNOS, Kim-1 and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of kidney. All these features of APAP toxicity were reversed by the co-administration of HD. Therefore, our study favors the view that HD may be a useful modulator in alleviating APAP induced oxidative stress and toxicity.

Altered antioxidant status and lipid peroxidation in Indian patients with urothelial bladder carcinoma

OBJECTIVES Urothelial carcinoma of bladder is the second most common urological malignancy after prostate cancer. Recently, there has been increased interest in research of the role of free radicals and antioxidant materials in the prevention, treatment, and alleviation of therapy-related side effects of cancer. In the present study, we aimed to assess the alterations in the levels of antioxidant vitamins, activities of defense enzymes, circulating lipid peroxide, and total antioxidant activity (AOA) in patients with urothelial carcinoma of bladder and correlate these changes with the grade and severity of the disease. MATERIALS AND METHODS The study cohort consisted of 90 subjects; 50 patients with bladder UC (25, low grade; 10, high grade; 15, muscle invasive) and 40 healthy controls. Vitamins C and E, malondialdehyde (MDA), and AOA were estimated using standard protocols. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed using commercially available kits. RESULTS The serum levels of vitamins C and E, whole blood levels of SOD and GPx, and serum AOA was significantly lower (P < 0.001) while serum MDA levels were significantly higher (P < 0.001) in patients than in controls, indicating presence of oxidative stress in bladder UC patients. The levels of all the biochemical parameters were correlated with the grade and severity of the disease. There were significant differences between the patients with low grade tumors and muscle invasive tumors for all parameters (P < 0.001); except AOA (P < 0.279). CONCLUSIONS The observed redox imbalance in UC of bladder in correlation with the grade and stage, as a consequence of decreased levels of antioxidant vitamins, enzymes, and AOA, along with increased MDA levels in circulation, may be important factors in tumor development and growth. Our results suggest that with advancing stage of bladder UC, the levels of oxidative stress increase, while levels of antioxidant molecules decrease. These findings suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of bladder cancer.

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. Our recent studies have suggested an association of sperm-associated antigen 9 (SPAG9) with ovarian carcinomas. In the present study, we investigated the clinical relevance of SPAG9 in RCC patients. RT-PCR analysis showed expression of SPAG9 transcript in RCC tissues and RCC cell lines. In situ RNA hybridization and immunohistochemistry analyses confirmed the expression of SPAG9 in 88% of cancer patients, suggesting that SPAG9 participates in renal cancer. In addition, immunoblotting and ELISA analyses revealed a humoral immune response against SPAG9 in the sera of RCC patients but not in healthy individuals. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a SPAG9 siRNA plasmid significantly inhibited tumor growth. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer. These results indicate that SPAG9 may have a role in tumor development and metastasis and thus could serve as a novel target for early detection and treatment of RCC.

Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype:

Background Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. Purpose To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. Material and Methods The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm2) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. Results There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 × 10−3 mm2/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 × 10−3 mm2/s) (P = 0.005). ADC values higher than 1.7960 × 10−3 mm2/s were seen only with low grade and values greater than 1.4904 × 10−3 mm2/s were seen only with clear-cell RCC. Conclusion ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other tumor attributes contributing to the variation in ADC values of RCCs.