Nk Mohanty

Serum Th1 and Th2 cytokine balance in patients of superficial transitional cell carcinoma of bladder pre- and post-intravesical combination immunotherapy

Combination therapy with intravesical bacillus Calmette-Guerin (BCG) plus interferon-α2b (IFN-α2b) for superficial transitional cell carcinoma (TCC) seems to be immune-dependent and activation of Th1 immune response is required for clinical efficacy. The present study evaluates circulating serum cytokine profiles (Th1/Th2 cytokines IFN-γ, IL-2 TNF-α, IL-4, IL-6 and IL-10) in 41 bladder cancer patients prior to transurethral resection of tumor (TURBT) (pre-therapy), and following intravesical combination immunotherapy (post-therapy) and their association with recurrence. Mean levels of IL-2 and TNF-α were significantly reduced while IL-4, IL-6 and IL-10 were significantly enhanced in pre-therapy samples as compared to controls. Mean levels of IFN-γ, IL-2 and TNF-α were significantly increased while IL-4 and IL-10 were significantly reduced in patients after instillation of combination immunotherapy. These findings suggest that bladder cancer patients develop Th2 dominant status with deficient type 1 immune response that shows tendency to reversal following therapy.

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder—our experience

INTRODUCTION The incidence of bladder malignancy is increasing worldwide and the projected rise is 28% by 2010 for both sexes (according to the WHO). Though intravesical adjuvant therapy with bacillus Calmette-Guérin (BCG) is superior to any other immunotherapeutic/chemotherapeutic agent in reducing tumor recurrences and disease progression, its real efficacy remains controversial as one-third of the patients will soon develop BCG failure. Hence, there is a need for an alternative intravesical agent for treatment of BCG failure. Our aim is to study the efficacy, tolerability, and safety of intravesical gemcitabine in managing BCG refractory superficial bladder malignancy. MATERIAL AND METHODS Thirty-five BCG failure patients, 26 males and 9 females between 20 and 72 years of age were instilled 2000 mg of gemcitabine in 50 ml of normal saline intravesically 2 weeks post-tumor resection, for 6 consecutive weeks. Mean follow-up for 18 months with cystoscopy was done. RESULT Twenty-one patients (60%) showed no recurrences, 11 patients (31.4%) had superficial recurrences, while 3 patients (8.75%) progressed to muscle invasiveness. Average time to first recurrence was 12 months and to disease progression was 16 months. Adverse event was low and mild. Therapy was well tolerated. CONCLUSION Gemcitabine fulfills all requirements as an alternative agent in treating BCG failure patients with low adverse events, well tolerated, and highly effective in reducing tumor recurrences.

Photoselective vaporization of prostate vs. transurethral resection of prostate: A prospective, randomized study with one year follow-up

Objectives: To evaluate in a prospective, randomized study, the efficacy and safety profile of photoselective vaporization of prostate (PVP) using a 80W potassium titanyl phosphate (KTP) laser when compared to standard transurethral resection of prostate (TURP) in patients with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). Materials and Methods: Between February 2009 and August 2009, 117 patients satisfying the eligibility criteria underwent surgery [60 PVP{Group A}; 57 TURP{Group B}]. The groups were compared for functional outcome (both subjective and objective parameters), perioperative parameters and complications, with a follow up of one year. P value<0.05 was considered statistically significant. Results: The baseline characteristics of the two groups were comparable. Mean age was 66.68 years and 65.74 years, mean IPSS score was 19.98 and 20.88, mean prostate volume was 44.77 cc and 49.02 cc in Group A and B, respectively. Improvements in IPSS, QOL, prostate volume, Q max and PVRU at 12 months were similar in both groups. PVP patients had longer operating time, lesser perioperative blood loss, shorter catheterization time and a higher dysuria rate when compared to TURP patients. The overall complication rate was similar in the two groups. Conclusions: In patients with LUTS due to BPE, KTP-PVP is an equally efficacious alternative to TURP with durable results at one year follow up with additional benefits of lesser perioperative blood loss, lesser transfusion requirements and a shorter catheterization time. Long term comparative data is awaited to clearly define the role of KTP-PVP in such patients.

A prospective randomized comparison between early (<48 hours of onset of colicky pain) versus delayed shockwave lithotripsy for symptomatic upper ureteral calculi: a single center experience.

BACKGROUND AND PURPOSE The role of early/emergency shockwave lithotripsy (SWL) in symptomatic upper ureteral calculi has still not been established. We have performed a randomized comparison between early (<48 hours) vs delayed (>48 hours) SWL for symptomatic upper ureteral stones less than 1 cm to evaluate the feasibility, safety, and efficacy of early SWL in these patients. PATIENTS AND METHODS One hundred and sixty consecutive patients with a single radiopaque upper ureteral stone <1 cm, who presented with an episode of colicky pain and who were undergoing treatment between July 2008 and June 2009 in our department were included. The patients were hospitalized and randomized into two groups-group A: SWL was performed within 48 hours of onset of colicky pain (early SWL) using the electromagnetic lithotripter (Dornier Alpha Compact) along with analgesics and hydration therapy; group B: SWL was performed after 48 hours (delayed SWL) along with analgesics and hydration therapy. The statistical analysis was performed in two groups regarding the patient demographic profile, presence of hydronephrosis, time to stone clearance, success rates, number of sessions needed, auxiliary procedures, modified efficiency quotient (EQ), and complications. RESULTS Eighty patients were enrolled in each group. The mean stone size was 7.3 mm in group A vs 7.5 mm in group B (P = 0.52). The stone fragmentation rate was 88.75% in group A vs 91.2% in group B (P = 0.35). The overall 3-month stone-free rate was 86.3% (69/80) for group A vs 76.2% (61/80) for group B (P = 0.34). The mean time taken for stone clearance was significantly less in group A than in group B (10.2 days vs 21.1 days; P = 0.01). The number of sessions needed in group A were significantly less than in group B (1.3 vs 2.7; P = 0.01). The auxiliary procedure rate was also significantly lesser in group A than group B (16.3% vs 32.5%; P = 0.001). The modified EQ (in %) was 67.2 in group A vs 59.4 in group B (P = 0.21). The steinstrasse formation and requirement for percutaneous nephrostomy (PCN) were significantly less in group A (P:0.02 and P:0.01 respectively). CONCLUSIONS Early SWL (within 48 hours of onset of colicky pain) is feasible, safe, and highly efficacious in the management of symptomatic proximal ureteral stones <1 cm, resulting in a lesser requirement of number of SWL sessions, time taken for stone clearance, auxiliary procedure rate, and fewer complications in comparison with delayed SWL.

Role of Tumor Suppressor and Angiogenesis Markers in Prediction of Recurrence of Non Muscle Invasive Bladder Cancer

Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a χ2 and Fisher’s Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105[2.624(1.274-5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993-4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148-4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611(1.189-5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021-5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n = 33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours.

Gene expression profile and mutational analysis of DNA mismatch repair genes in carcinoma prostate in Indian population.

DNA mismatch repair (MMR) plays a role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between nonidentical DNA sequences, and participating in responses to DNA damage. Although the role of MMR in prostate carcinogenesis remains unclear, MMR deficiency in Carcinoma Prostate (Pca) could prove to be clinically significant. Thus, the present study investigated the gene expression profile of six major MMR genes, viz. hMLH1, hMSH2, hPMS1, hPMS2, hMSH3, and hMSH6, and polymorphism in hMLH1 and hMSH2 in Pca in Indian population. Further, correlation with clinicopathological parameters was evaluated to establish their role as a potential prognostic marker. A significant downregulation of hMLH1, hMSH2, and hPMS2 expression was observed in Pca compared to benign prostatic hyperplasia (BPH). A greater loss of hPMS2 protein in poorly differentiated tumors was demonstrated, which was in concordance with a significant inverse correlation of hPMS2 gene expression with the Gleason score indicating its significance as a marker for Pca progression. An important association of hMLH1-93G>A polymorphism with the risk of Pca was also identified. The results of the present study suggest that an altered MMR has important biological and clinical significance in Pca in Indian population.

Association of androgen receptor, prostate-specific antigen, and CYP19 gene polymorphisms with prostate carcinoma and benign prostatic hyperplasia in a north Indian population

The genes involved in androgen pathway and metabolism have been reported to contribute considerably to prostate carcinoma (CaP) risk. The present study investigated the association of androgen receptor (AR), prostate-specific antigen (PSA or KLK3), and cytochrome P450 (CYP19) gene polymorphisms in CaP (n=105) and benign prostatic hyperplasia (BPH) (n=120) in comparison to normal healthy controls (n=106) in an Indian population. We also evaluated the functional consequences of these gene variants on AR and PSA mRNA expression. Significant association of short AR CAG repeats (≤24) with risk of CaP (odds ratios [OR]=2.98, p<0.001) and BPH (OR=1.96, p=0.01) was observed; however, CYP19 gene polymorphism was not found to be associated with disease phenotype (p>0.05). PSA G-158A SNP was found to be significantly associated with risk of CaP (AA: OR=2.68, p=0.016 and GA: OR=2.07, p=0.018) p-trend 0.031 and BPH (AA: OR=3.46, p<0.001 and GA: OR=2.47, p=0.03) p-trend 0.009, respectively. PSA G-158A genotype independently increased the risk of developing BPH (OR=16.37, p<0.001), irrespective of AR CAG repeat length. Using quantitative real-time polymerase chain reaction, we found a significant upregulation of AR and PSA mRNA expression in CaP comparison to BPH. While short AR CAG (≤24) repeats were associated with higher AR mRNA expression in CaP (p=0.002), the PSA SNP did not correlate with its mRNA expression. Interestingly, significantly higher risk estimates for CaP were observed for the combined analysis of short AR CAG and CYP19 genotypes (A2A2) (OR=7.18, p<0.001) or A2A3 (OR=7.60, p=0.004). Our results suggest significant association of androgen signaling gene polymorphisms with risk of CaP and BPH and provide evidence for a putative functional role of AR CAG repeat in regulating its mRNA expression and warrant the need of larger studies in the Indian population to confirm our results.

Role of botulinum toxin-A in management of refractory idiopathic detrusor overactive bladder: Single center experience

Background Overactive bladder (OAB) is a bothersome condition affecting the quality of life, financial constraint on the individual, and community. Anticholinergic drugs cannot be used for long term due to adverse side effects. Botulinum toxin has recently shown promising and encouraging result in management of OAB. Aim Aim was to study the safety, efficacy, tolerability, and duration of effect of 200 units of botulinum toxin in refractory idiopathic detrusor overactivity. Materials and Methods Thirty-nine female patients (average age of 52 years) clinically and urodynamically diagnosed as idiopathic OAB were injected 200 units of botulinum toxin-A mixed with 20 ml of normal saline, intradetrusally at the rate of 1 mL at each site for 20 such sites sparing the trigone and ureteric orifices. Follow up at 3rd, 6th, 9th, and 12th month with clinical and urodynamical questionnaire was done. Results There were 4 dropouts and 35 patients were evaluated, of which 30 patients (85.7%) showed improvement in clinical features like frequency, urgency, nocturia, and incontinence within 1 week of injection, which lasted for mean period of 7 months (varying from 6 to 9 months). Volume at first desire to void improved from median baseline of 104-204 ml and maximum cystometric capacity of bladder increased from mean baseline value of 205-330 ml. The detrusor pressure decreased by 49% from the baseline and postresidual urine volume increased by 30% of maximum cystometric capacity of bladder. There was no adverse effect on our patient. Conclusion Intradetrusor injection of Botox-A in management of refractory overactive idiopathic bladder is not only safe and well tolerated, but also very effective with practically no side effects.

Altered Expression of Succinic Dehydrogenase in Asthenozoospermia Infertile Male

There is a possibility that mitochondrial respiration defects may contribute to asthenozoospermia.

Management of BCG non-responders with fixed dose intravesical gemcitabine in superficial transitional cell carcinoma of urinary bladder

Aims and Objectives: The incidence of bladder malignancy is increasing worldwide and the projected rise is 28% by 2010 for both sexes (WHO). Though intravesical adjuvant therapy with BCG is superior to any other immunotherapeutic/chemotherapeutic agent in reducing tumor recurrences and disease progression, its real efficacy remains controversial as one-third of the patients will soon become BCG failure. Hence there is a need for an alternative intravesical agent for treatment of BCG failure. Our aim was to study the efficacy, tolerability and safety of intravesical Gemcitabine in managing BCG-refractory superficial bladder malignancy. Materials and Methods: Thirty-five BCG failure patients, 26 males and nine females between 20-72 years of age were instilled with 2000 mg of Gemcitabine in 50 ml of normal saline intravesically two weeks post tumor resection, for six consecutive weeks. Mean follow-up was for 18 months with cystoscopies. Results: Twenty-one patients (60%) showed no recurrences, 11 patients (31.4%) had superficial recurrences while three patients (8.6%) progressed to muscle invasiveness. Average time to first recurrence was 12 months and to disease progression was 16 months. Adverse event was low and mild. Therapy was well tolerated. Conclusion: Gemcitabine fulfils all requirements as an alternative agent, in treating BCG failure patients with low adverse events, is well tolerated and highly effective in reducing tumor recurrences.