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Byline: Ankush. Modi, Prabhjot. Singh, Amlesh. Seth, Rajeev. Kumar Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA [...]

Objectives: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM–DKI) and their machine‐learning‐based texture analysis for the detection and assessment of severity in prostate cancer (PCa). Materials and methods: Eighty‐eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM–DKI data were acquired using 13 b values (0–2000 s/mm2) and analyzed using the IVIM–DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One‐way analysis‐of‐variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM–DKI parameters. A chi‐square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM–DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. Results: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = −0.33; D, ρ = −0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM–DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. Conclusion: D, f, and k computed using the IVIM–DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM–DKI parameters showed high accuracy and AUC in PCa detection. [ABSTRACT FROM AUTHOR]

The Corona Virus Disease-2019 (COVID-19), one of the most devastating pandemics ever, has left thousands of cancer patients to their fate. The future course of this pandemic is still an enigma, but health care services are expected to resume soon in a phased manner. This might be a long drawn process and we need to have policies in place, to be able to fight both, the SARS-CoV-2 virus and cancer, simultaneously, and emerge triumphant. An extensive literature search for impact of delay in management of various urological malignancies was carried out. Expert opinions were sought wherever there was paucity of evidence, in order to reach a consensus and come up with recommendations for directing uro-oncology services in the times of COVID-19. The panel recommends deferring treatment of patients with renal cell carcinoma by 3 to 6 months, except for those with ongoing hematuria and/or inferior vena cava thrombus, which warrant immediate surgery. Metastatic renal cell cancers should be started on targeted therapy. Low grade non-muscle invasive bladder cancers can be kept on active surveillance while high risk non-muscle invasive bladder cancers and muscle invasive bladder cancers should be treated within 3 months. Neoadjuvant chemotherapy should be avoided. Management of low and intermediate risk prostate cancer can be deferred for 3 to 6months while high risk prostate cancer patients can be initiated on neoadjuvant androgen deprivation therapy. Patients with testicular tumors should undergo high inguinal orchiectomy and be treated according to stage without delay, with stage I patients being offered surveillance. Penile cancers should undergo penectomy, while clinically negative groins can be kept on surveillance. Neoadjuvant chemotherapy should be avoided and adjuvant therapy should be deferred. We need to tailor our treatment strategies to the prevailing present conditions, so as to fight and defeat both, the SARS-CoV-2 virus and cancer. Protection of health care workers, judicious use of available resources, and a rational and balanced outlook towards different malignancies is the need of the hour. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Methods: Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnosticGa-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and ttoxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. Results: The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity. Conclusion: Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess the accuracy of Gleason grading/scoring on preoperative needle core biopsy (NCB) compared to the radical prostatectomy (RP) specimen. Materials and Methods: Data of NCB and RP specimens was analyzed in 193 cases. Gleason grade/scoring was done on both NCB and RP specimens. Sixteen cases were excluded for various reasons. The Gleason scores of the two sets of matched specimens were compared and also correlated with the PSA, age, and number of needle biopsy cores. The overall change was also correlated with the initial score on NCB. Results: The mean age and PSA were 63.3 ± 2(5.27) years and 18.48 ± 2(28.42) ng/ml, respectively. The average Gleason score increased from 5.51 ± 2(1.52) to 6.2 ± 2(1.42) ( P < 0.02). The primary grade increased in 57 (32.2%) cases. Overall, 97 (54.8%) cases had an increase in Gleason score. Five other cases had a change from 3 + 4 = 7 to 4 + 3 = 7. Change in Gleason score was significantly more if the score on NCB was ≤ 6 or number of needle cores was ≤ 6. Besides, 28 cases had perineural invasion, 16 had capsular invasion (pT3a), and 4 had vascular invasion on RP specimen. Conclusions: There is a significant upgrading of Gleason score on RP specimens when compared with NCB. This trend may be correlated positively with lower initial Gleason score on preoperative biopsy and the lower number of cores taken. [ABSTRACT FROM AUTHOR]

Primary prostatic lymphomas are extremely unusual neoplasms. Their rarity and nonspecific symptomatology at presentation usually prompt a clinical diagnosis of benign prostatic hyperplasia or chronic prostatitis, leading to significant delay in diagnosis. Clinical examination, serum prostate-specific antigen levels, and transrectal ultrasonography (TRUS) are not of much utility in differential diagnosis, and histological examination is the gold standard. We report two cases of primary non-Hodgkin lymphoma of prostate, diffuse large B-cell type, diagnosed on TRUS-guided prostatic biopsies. Correct diagnosis is of crucial importance as the therapeutic strategy for lymphoma is radically different from that for carcinoma, and early detection of prostatic lymphoma can be potentially curative. Thus, knowledge of this rare entity, inclusion in differential diagnosis of lower urinary tract obstruction, and application of an appropriate immunohistochemical panel are essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

To compare the efficacy of orchiectomy alone and orchiectomy plus flutamide in treating patients with advanced carcinoma prostate.The study was initiated on 1 July 1997 and closed after enrolling 100 patients on 30 June 2000. Patients were prospectively randomized to orchiectomy alone (O) and orchiectomy plus flutamide (OF). A complete response (CR) was defined as the normalization of bone scans and serum prostate-specific antigen (PSA) levels returning to normal (<4 ng/mL). A partial response (PR) was defined as a 50% reduction in metastasis mass compared to the initial study or a decrease in the PSA level of 50% of the initial value. Progressive disease (PD) was defined as the development of any new hot spot on bone scan or any increase in previously existing PSA level by 25%.A total of 100 patients were entered in the study. The maximum percentage change in PSA levels in both groups was found in the first 3 months after orchiectomy, that is, 95% and 97% for the O and OF groups, respectively. In more than 80% of the patients this decrease in PSA was maintained for 3 years. The mean percentage change at 3 years in the O and OF groups was 70% and 75% (P = 0.95), respectively, and the overall response rate (CR + PR) was 88.50% and 86.53% in the two groups, respectively (P = 0.85). The follow-up period ranged between 3 and 5 years (mean, 3.5 years). The mean time to progression was 27 and 29 months in the O and OF groups, respectively. The overall survival rate at 3 and 5 years in two treatment groups was 45.83% and 48.07%, 20.83% and 23.07% in the O and OF groups, respectively (P = 0.75).Maximum percentage decrease in PSA is seen within the first 3 months of therapy. Orchiectomy alone is as effective as combination therapy in decreasing serum PSA. Overall survival at 3 and 5 years in the orchiectomy only group was as good as that of combination therapy. These data suggest that the routine addition of flutamide to orchiectomy is not advisable. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the role of GSTM1 and T1 null genotypes as risk factors for prostate cancer in north Indian population. Methods: The subjects appraised were 150 cases and 172 healthy males. Peripheral blood was collected along with the demographic and anthropometric data. DNA was extracted by proteinase K/SDS digestion and GSTM1 and GSTT1 polymorphisms were analyzed by a multiplex-PCR. Results: GSTM1 and GSTT1 null genotype was found to confer 2.45 (OR= 2.45; 95% CI = 0.56-3.82; P-value=0.00008) and 2.39 (OR=2.39; 95% CI=1 36-4.20; p-value=0.02) fold higher risk of prostate cancer independent to each other. Also, null genotype at either loci, GSTM1 or GSTT1, increased the risk by 2.84 folds (OR=2.84; 95% CI=1.76-4.51; P value= 0.0002).The null genotype at both loci was assessed to be a significant risk factor of prostate cancer (OR= 4.08, 95% CI= 1.93-8.61, P value = 0.0002). Smoking imparted a 2.08 fold higher risk of prostate cancer (OR=2.08, 95% CI=1.31-3.30, P value = 0.00002). Factors like alcohol consumption, tobacco chewing, consumption of vegetarian/ non-vegetarian food, literacy levels, occupation pursued and residential locality were not found to be significant in risk prediction. Conclusions: GSTM1 and GSTT1 null genotypes and smoking are associated with high risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Introduction: ELAC-2 gene is considered as prostate cancer susceptibility gene. It is located on chromosome 17p11 and is encoded as HPC/ELAC2. Two common polymorphisms i.e. Ser217Leu and Ala541Thr are apparently associated with a modestly increased risk in familial prostate cancer. According to Xu et al. (2006), Ala541Thr polymorphism was not frequent either in control or in sporadic cases of prostate cancer in Americans. The frequency of heterozygous (Ala/Thr) was low in all the groups and homozygous (Thr/Thr) was an occasional occurrence. On the other hand, the Ser217Leu polymorphism has been found to be associated with prostate cancer in familial cases as well as in sporadic cases (Xu et al., 2001). The present study was conducted to find out the association of Ser241Leu genotype in cases of sporadic prostate cancer in Indian population. Methods: In Indian population the number of prostate cancer with familial history was quite negligible. Hence genotype analysis of HPC/ELAC-2 was done on 157 cases of sporadic prostate cancer and 170 age matched controls (having normal serum PSA < 4.0ng/ml and normal digital rectal examination) using RFLP technique. Results: Leu217 homozygous genotype (Leu/Leu) had shown 1.7 fold (0.74-3.92) increased risk of prostate cancer. When data was stratified with staging, the risk was aggravated to 1.86 in metastized cases (95% CI=0.70-4.96). Smokers (OR=3.24; 95% CI=0.80-13.18) and non vegetarians (OR=2.92; 95% CI=0.76-11.24) were at higher risk in developing prostate cancer with this mutant genotype (Leu/Leu). Conclusions: This study stresses the role of gene-environment interaction in the progression and development of prostate cancer. The results were similar to European American population done by Wheeler et al. (2006) indicating its role in the etiology and clinical progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Metastatic burden and aggressive behavior determine severity stratification and guide treatment decisions in prostate cancer (PCa). Monoamine oxidase A (MAOA) may promote tumor burden and drug/castration resistance in PCa. A positive association will pave the way for MAOA inhibitors such as moclobemide for PCa therapy. To analyze MAOA in peripheral blood mononuclear cells qualitatively and p38, c-Jun N-terminal kinases, nuclear factor kappa B, and their phosphorylated forms, vascular endothelial growth factor (angiogenesis), transforming growth factor beta, interleukin 6, and tumor necrosis factor-α (cytokines), Bcl-2 associated X, B-cell lymphoma 2, and P53 (apoptosis), prostate-specific membrane antigen, and epithelial cell adhesion molecules (surface markers) in plasma of patients with PCa. This was a 1-year pilot study in which patients with PCa were recruited and stratified into 2 groups and subgroups: treatment-naive with (M1) (n = 23) or without (M0) (n = 23) bone metastasis; hormone-sensitive prostate cancer (n = 26) or hormone/castration-resistant prostate cancer (n = 26). MAOA was detected using ELISA and other proteins were detected using immunoblotting technique. MAOA was detected in 8.6% of M0 compared with 30.4% of M1 patients, and in 7.7% of hormone-sensitive compared with 27% of hormone/castration resistant PCa patients, associating it with bone metastasis and castration resistance. Multivariable regression analysis showed a correlation of MAOA with serum prostate-specific antigen, a marker for progression in PCa (Pearson correlation coefficient r = 0.30; P < 0.01). In patients with positive MAOA, there was overexpression of p38, phosphorylated-p38, c-Jun N-terminal kinases, phosphorylated c-Jun N-terminal kinases, nuclear factor kappa B, phosphorylated nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, interleukin 6, tumor necrosis factor α, Bcl-2 associated X, B-cell lymphoma 2, prostate-specific membrane antigen, and epithelial cell adhesion molecule in M1 compared with M0 group patients, associating these proteins with tumor burden. Overexpression of Bcl-2 associated X, tumor protein 53, c-Jun N-terminal kinases, nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, and prostate-specific membrane antigen and underexpression of B-cell lymphoma 2 and phosphorylated nuclear factor kappa B were observed in hormone-sensitive prostate cancer compared with hormone/castration-resistant prostate cancer, associating these proteins with castration resistance. Association of key molecules of oncogenesis and metastasis with MAOA suggests that MAOA inhibitors such as moclobemide might be effective in the management of PCa. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract: Adenoid cystic carcinoma is an unusual histological variant of prostatic carcinoma. Because of its rarity, the natural history of this tumor is not known. Here we report this rare entity in a 62-year-old man who presented with symptoms of urinary tract obstruction. Digital rectal examination and ultrasonography (USG) showed an enlarged hard nodular prostate. Serum prostate-specific antigen (PSA) and prostatic acid phosphate levels were found to be within the normal range. Transrectal ultrasound-guided 12 core biopsies of prostate showed morphological features of an adenoid cystic carcinoma in 8 cores (bilateral, mid and base) on histopathological examination. Immunohistochemistry performed for PSA on paraffin section was negative. After diagnosis, bilateral orchidectomy was performed, and hormonal therapy was started in the form of androgen receptor blocker. The patient was clinically stable during a limited follow up of six months. [Copyright &y& Elsevier]

Abstract: Objectives: Bladder cancer is a common tumor of the urinary tract, accounting for 6% to 8% of all male malignancies and 2% to 3% of all female malignancies. Urothelial carcinoma (UC) of bladder is the second most common urologic malignancy after prostate cancer. Earlier report has elucidated immunologic unreactivity in cancer patients. Cytokines play a pivotal role in the induction of cell mediated and humoral immunity. Quantification of cytokine response in cancer patients can give significant insights about the cellular immunologic potency against the neoplastic cells. In the present study, we aimed to assess alterations of Th1 and Th2 derived cytokines in progression of UC of bladder by determining their circulatory concentration in bladder cancer patients and healthy controls and to correlate the observations with grade and severity of the disease. Materials and methods: The study cohort consisted of 122 subjects; 72 patients with bladder UC (28, low grade; 17, high grade; 27, muscle invasive) and 50 healthy controls. The circulatory levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit from BD Biosciences, San Diego, CA, and were statistically correlated according to the grade and the severity of disease. Results: The serum levels of typical Th1 cytokines: IL-2 and IFN-γ were found to be significantly lower (P < 0.001) while levels of Th2 cytokines i.e., IL-4, IL-5, and IL-10 were significantly higher (P < 0.001) in patients than in controls. The levels of all the cytokines 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 cytokines (P < 0.001); except IL-10 (P < 0.626). Conclusions: The results of our study delineate that in bladder tumor patients a marked polarization exists towards the expression of Th2 type cytokines while Th1 remain suppressed. Furthermore, the levels of all the cytokines alter according to the grades of the tumor. This can give significant insights about the use of Th1 type cytokines for the administration of immunotherapy to bladder cancer patients. Development of new strategies attempting to manipulate the equilibrium between Th1 and Th2 cells would be beneficial in the management of UC of bladder in future. [Copyright &y& Elsevier]