Intravoxel incoherent motion and diffusion kurtosis imaging and their machine-learning-based texture analysis for detection and assessment of prostate cancer severity at 3 T.

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.

The prognostic role of preoperative neutrophil-to-lymphocyte ratio in upper tract urothelial carcinoma.

Introduction: The blood-based inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), is a reliable prognostic biomarker for several cancers. Although the literature supports the correlation between preoperative NLR, clinicopathological characteristics, and oncological outcomes in upper tract urothelial carcinoma (UTUC), the cutoff of NLR is still debated. This study aimed to determine the prognostic value of NLR in patients with UTUC. Methods: This was a retrospective analysis of prospectively collected data from July 2012 to December 2022 evaluating patients with UTUC who underwent radical nephroureterectomy (RNU). NLR was calculated using the neutrophil and lymphocyte counts obtained a day before the surgery and the cutoff value was set as 2.5. Kaplan-Meier and Cox's proportional hazards regression were used to analyze the association between NLR and the oncological outcomes. Results: The study included 91 patients (78 males, 13 females) in the final analysis with a median follow-up of 49 months (8-130). The mean age of the patients with NLR <2.5 and NLR ≥2.5 was 56.88 years and 56.35 years, respectively, and the pathological stage was pT1 in 48%, pT2 in 20.88%, pT3 in 27.47%, and pT4 in 3.30% of the patients. Multivariable Cox regression analysis showed that the preoperative NLR ≥2.5 was significantly associated (Hz = 7.17) with higher T stage, lymphovascular invasion, necrosis, nodal involvement, adjuvant chemotherapy, and worse overall survival (OS) (Hz = 9.87). The Kaplan-Meier analysis revealed an improved OS in patients with NLR <2.5, but a statistically significant difference in the recurrence-free survival was not found. Conclusions: Preoperative NLR is an easily available, inexpensive, and important prognostic biomarker of survival in patients with UTUC and has a potential role in risk stratification by predicting adverse clinicopathological characteristics.

Multimodality imaging evaluation of pseudotumors in chronic renal dysfunction: exposing the masquerade!

Focal renal lesions in the background of chronic kidney disease (CKD) present a diagnostic challenge. Contrast administration is usually avoided in such a setting, undermining the usefulness of computed tomography and magnetic resonance imaging. Focal regenerating nodules may occur in the background of CKD and closely mimic renal neoplasms. The aim of the present article was to highlight the salient manifestations of such CKD pseudotumors on different imaging modalities and also to depict the differentiating features from malignancy. Radiologists must be aware of the imaging appearance of this uncommonly talked about entity so as to avoid inadvertent surgery or cause undue anxiety to the patient.

Role of Contrast-Enhanced Ultrasound in Evaluation of Cystic Renal Mass.

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) allows excellent delineation of perfusion in septa and nodules without exposure to ionizing radiation or nephrotoxic contrast media. The aim of our study was to evaluate the role of CEUS for the assessment of cystic renal masses and compare its diagnostic performance with that of CECT. METHODS: Exactly 40 patients diagnosed to have cystic renal masses on CECT scan were prospectively evaluated with CEUS and were assigned a Bosniak class. Based on results of final histopathology and clinical follow-up, internal validity of both CEUS and CECT was evaluated, including agreement between these two modalities. RESULTS: Out of the 40 patients (mean size 3.1 ± 2.5 cm), 23 patients had benign lesions and 17 patients had malignant lesions. For CEUS, the sensitivity and negative predictive value was 100%, the specificity and positive predictive value was 73.9%. For CECT, the sensitivity and negative predictive value were 88.2 and 83.3%, respectively, whereas the specificity and positive predictive value was 87 and 90.9%, respectively. Both imaging modalities had similar accuracy with fair to good agreement with the final diagnosis (Κ = 0.71 and 0.75 for CEUS and CECT, respectively). Concordance between CEUS and CECT was seen in 29 patients (72.5%) with fair agreement between the two modalities (K = 0.66). CONCLUSION: CEUS has comparable accuracy with CECT and could be used as screening modality to rule out the presence of complex cystic renal masses without exposure of nephrotoxic contrast media and ionizing radiation.

Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study.

Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with "elevated" PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. Methods: In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. Results: During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14-15.6), and the median follow-up PSA was 5.08 (IQR: 3.18-8.4). At a median follow-up of 53 months (range: 6-77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. Conclusions: PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.

Association of heavy metals and trace elements in carcinoma urinary bladder: A case-controlled study.

Introduction: Abnormal levels of heavy metals (HM) and trace elements (TE) affect body metabolism and can induce carcinogenesis. This study aims to evaluate the role of HM and TE in carcinoma urinary bladder (CAUB). Methods: Patients with biopsy-proven CAUB (n = 100) were taken as the study group, while age-and sex-matched healthy volunteers were taken as control (n = 100). Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb), and Mercury (Hg) levels. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels were assessed to know the redox status between the two groups. Results: A significantly higher blood level of As, Mn, and Pb was observed in CAUB cases as compared to controls. Blood Se level was significantly lower in CAUB patients. On comparing urinary levels, CAUB patients had a higher As, Mn, and Pb levels compared to controls. Further, 68% and 59% of patients had their blood and urinary HM and TE levels above the permitted level, respectively. CAUB cases also had a lower GSH-Px (113.5 ± 44.7 vs. 163.9 ± 120.5, P = 0.0002), lower SOD levels (11.35 ± 5.6 vs. 13.75 ± 3.9, P = 0.008), and a higher LPO levels (15.5 ± 14.7 vs. 11.18 ± 11.2, P = 0.02) in the serum. Conclusions: A significantly higher concentration of As, Mn, and Pb was noted in the blood and urine of CAUB patients compared to controls. CAUB cases also had lower serum GSH-Px and SOD levels with a concomitant increased serum LPO assay suggesting underlying oxidative stress.

Autophagy-associated HMGB-1 as a novel potential circulating non-invasive diagnostic marker for detection of Urothelial Carcinoma of Bladder.

Urothelial carcinoma of bladder (UBC), a highly prevalent urological malignancy associated with high mortality and recurrence rate. Standard diagnostic method currently being used is cystoscopy but its invasive nature and low sensitivity stresses for identifying predictive diagnostic marker. Autophagy, a cellular homeostasis maintaining process, is usually dysregulated in cancer and its role is still enigmatic in UBC. In this study, 30 UBC patients and healthy controls were enrolled. Histopathologically confirmed tumor and adjacent normal tissue were acquired from patients. Molecular expression and tissue localization of autophagy-associated molecules (HMGB-1, RAGE, beclin, LC-3, and p62) were investigated. Serum HMGB-1 concentration was measured in UBC patients and healthy controls. ROC curves were plotted to evaluate diagnostic potential. Transcript, protein, and IHC expression of HMGB-1, RAGE, beclin, and LC-3 displayed upregulated expression, while p62 was downregulated in bladder tumor tissue. Serum HMGB-1 levels were elevated in UBC patients. Transcript and circulatory levels of HMGB-1 showed positive correlation and displayed a positive trend with disease severity. Upon comparison with clinicopathological parameters, HMGB-1 emerged as molecule of statistical significance to exhibit association. HMGB-1 exhibited optimum sensitivity and specificity in serum. The positive correlation between tissue and serum levels of HMGB-1 showcases serum as a representation of in situ scenario, suggesting its clinical applicability for non-invasive testing. Moreover, optimum sensitivity and specificity displayed by HMGB-1 along with significant association with clinicopathological parameters makes it a potential candidate to be used as diagnostic marker for early detection of UBC but requires further validation in larger cohort.

Raised prostate-specific antigen alone may not be a true predictor in high-risk prostate cancer: A retrospective cohort analysis.

INTRODUCTION: Prostate-specific antigen (PSA) >20 ng/mL in isolation is a criterion for classification as "high-risk" prostate cancer (PCa). However, among Indian men, PSA elevation is often seen even in the absence of PCa and patients with PSA as the sole criterion for the high-risk disease may have different outcomes from those categorized as high risk due to adverse pathological features. We compared the operative, oncological, and functional outcomes after robot-assisted radical prostatectomy (RARP) in men with high-risk PCa categorized using PSA alone versus clinical and histopathological findings. MATERIALS AND METHODS: In an Institute Review Board-approved study, men undergoing RARP with high-risk PCa with at least 2-year follow-up were categorized into those with PSA >20 ng/ml being the sole criteria for being high risk (Group A) versus those with Gleason score ≥8 or ≥T2c disease but any PSA level (Group B). The two groups were compared for perioperative, oncological, and functional outcomes. RESULTS: Fifty-three patients with high-risk disease were included. Twenty-six patients (48.9%) were classified into Group A while 27 patients (50.9%) were classified into Group B. The median PSA was significantly higher in Group A (31 [26-35] ng/ml in Group A vs. 21 [12-34] ng/ml in Group B, P = 0.006) and on histopathology of radical prostatectomy specimen, 24 (92.3%) patients had GG ≤3 disease in Group A versus 10 (37%) patients in Group B (P < 0.001). Patients in both the groups had similar perioperative and continence outcomes. However, Group A had significantly lower biochemical recurrence rate (3/26 [11.5%]) as compared to Group B (11/27 [40.7%]) (P = 0.012). CONCLUSIONS: PSA >20 ng/ml is the single most common criterion for stratification as high-risk PCa. However, men with PSA >20 ng/ml in isolation, without another adverse criterion, have better outcomes than men with adverse clinical or pathological criteria for high-risk disease.

Association of human papillomavirus in penile cancer: A single-center analysis.

Introduction: Human papillomavirus (HPV) is a known risk factor of penile cancer (PeCa). However, studies evaluating its true association are limited. In this study, we aimed to estimate HPV prevalence and its true association with PeCa in terms of molecular biological activities. Materials and Methods: This single-institutional prospective observational study was conducted between June 2016 and August 2019. We included 40 men with PeCa as a study group and 20 age-matched uncircumcised men who underwent circumcision for phimosis as a control group. Both the groups underwent deoxyribonucleic acid isolation for HPV subtyping followed by evaluation of relative E6/E7 messenger ribonucleic acid (mRNA) expression profile and relative telomerase activity in tissue samples. HPV-16 and -18 were categorized as high-risk, whereas HPV-6 and -11 were categorized as low-risk subtypes. Results: The mean (±standard deviation) age of PeCa was 51 ± 15.9 years. The majority of patients had stage II disease, and the most common procedure done was partial penectomy. The overall prevalence of HPV in PeCa was 42.5% (n = 17) as compared to 20% (n = 4) in controls. Among the subtypes, the most common subtype was HPV-16 noted in 33.3% (8/24) of cases, followed by HPV-18 in 29.2% (7/24) of cases. PeCa tissues had a significantly higher relative E7 mRNA expression for HPV-18 than the control group (P = 0.016). The mean relative telomerase activity was significantly higher in the PeCa tissues than the control group (138.66 vs. 14.46, P < 0.001). A significantly higher relative telomerase activity was noted in the PeCa tissues positive for high-risk HPV subtypes than controls (141.90 vs. 14.46, P = 0.0008), but not between high-risk HPV-positive and HPV-negative PeCa cases (141.90 vs. 137.03, P = 0.79). High-risk subtypes were not associated with tumor stage (P = 0.76) or lymph node metastasis (P = 0.816). Conclusions: HPV was associated in 42.5% of PeCa cases based on our experience from a single institution. PeCa tissues had a higher relative E7 mRNA expression for HPV-18 and relative telomerase activity as compared to controls suggesting their potential role as surrogate markers of virus-induced tumorigenesis.

Effects of horizontal versus vertical bolster alignment on anatomical orientation of kidney as applied to prone percutaneous nephrolithotomy.

PURPOSE: To evaluate the anatomical changes in kidney orientation in prone position with use of horizontal or vertical bolster alignment. METHODS: Patients having renal stone(s) on ultrasonogram or X-ray underwent split bolus computed-tomo-urography (CTU) in prone position with horizontal and vertical bolster positions. CTUs were read by a single radiologist to quantify the cranio-caudal, antero-posterior, side to side and rotational movements of kidneys as relevant to prone percutaneous nephrolithotomy. RESULTS: 19 adult patients with 38 renal units and mean basal metabolic index of 25.6 kg/m2 underwent CTU. Greater inferior displacement of both kidneys was seen with horizontal bolsters as compared to vertical bolsters. The right upper calyceal-diaphragm distance was 2.1 ± 1.5 cm and the lower calyceal-diaphragm distance was 2.0 ± 1.6 cm greater with the horizontal bolsters (p < 0.01). Similarly, the displacement on the left side was 1.5 ± 0.8 cm and 1.4 ± 0.8 cm, respectively (p < 0.01). Horizontal bolsters also result in significantly longer calyceal-skin distance at both poles of both kidneys [right upper: 0.4 ± 0.5 cm (p < 0.01), right lower: 0.8 ± 0.7 cm (p < 0.01), left upper: 0.4 ± 0.6 cm (p = 0.02), left lower: 0.8 ± 1.1 cm (p < 0.01)] and wider erector spinae-mid posterior calyceal-colon angle (124.8 v/s 110.0 on the right and 96.2 v/s 85.7 on the left) (p < 0.01). CONCLUSION: Horizontal bolsters provide significantly more caudal displacement of the kidneys; the right kidney being displaced more as compared to the left. However, there is also an increase in the skin-calyceal distance with horizontal as compared to the vertical bolsters. These assessments may help the surgeons decide optimal bolster position individualized to the patient.

Impact of vesicovaginal fistula repair on urinary and sexual function: patient-reported outcomes over long-term follow-up.

INTRODUCTION AND HYPOTHESIS: While the anatomical closure rates of vesicovaginal fistula (VVF) following transabdominal (TA) and transvaginal (TV) repairs seem comparable, studies comparing urinary and sexual outcomes following successful repair are lacking. We aimed to report patient-reported outcomes on sexual and urinary functions after long-term follow-up with successful repair. METHODS: We retrospectively reviewed 81 women who had successful VVF repair at our institute. Pre-, intra- and post-operative details were retrieved from electronic data software. Patient-reported sexual and urinary function outcomes were assessed using the Female Sexual Function Index (FSFI) questionnaire and International Consultation of Incontinence Questionnaire-Short Form (ICIQ-SF), respectively, at last follow-up. We also compared such outcomes among TA and TV repairs. RESULTS: Of 81 women, 28 (34.6%) had TA and 53 (65.4%) had TV repairs. Mean age was 37.5 years and mean fistula diameter was 12.9 mm. The most common aetiology was hysterectomy. Thirty-three patients (40.7%) had previous failed repairs. At a mean follow-up of 29.8 months, 24 (34.3%) women had sexual dysfunction and 15 (18.5%) women experienced urinary dysfunction. The TA and TV groups had comparable mean FSFI scores (28.7 ± 6.1 vs. 30.9 ± 5.2, p = 0.13) and ICIQ-SF scores (0.7 ± 1.7 vs. 0.5 ± 1.4, p = 0.59). In multivariate analysis, fistula size and site were significant predictors of urinary dysfunction whereas multiparity was the most significant predictor of sexual dysfunction. CONCLUSIONS: Sexual and urinary dysfunction is found in a considerable number of women after VVF repair. However, our data suggest comparable long-term sexual and continence outcomes between TA and TV repairs.

Refractory lymphatic ascites following laparoscopic management of renal lymphangiectasia: An unusual presentation.

Renal lymphangiectasia characterised by either unilocular or multilocular cystic lesion in and around the kidney is an uncommon condition. Presentation of these lesions is quite varied, which along with its uncommon occurrence adds to the challenges in the management of this condition. Most of these cases are managed conservatively and very rarely need any intervention. We present an unusual complication of refractory lymphatic ascites following laparoscopic deroofing of a unilocular renal lymphangiectasia in a 21-year-old gentleman who presented with left flank pain. The ascitic fluid analysis suggested non-chylous lymphatic ascites. The surgical outcome was rather exasperating for the patient than the disease itself. Hence, in the interest of the patient with minimal symptoms, if the imaging is highly suggestive of renal lymphangiectasia, either no intervention or the least invasive procedures should be attempted, whenever possible.

RASSF1A-Hippo pathway link in patients with urothelial carcinoma of bladder: plausible therapeutic target.

RASSF1A is a tumor suppressor gene, and its hypermethylation has been observed in cancers. RASSF1A acts as an upstream regulator of Hippo pathway and modulates its function. The aim of this study was to analyze expression of RASSF1A, Hippo pathway molecules (YAP, MST) and downstream targets (CTGF, Cyr61 and AREG) in bladder cancer patients. Later, the link between RASSF1A and Hippo pathway and a potential therapeutic scope of this link in UBC were also studied. MSPCR was performed to study methylation of RASSF1A promoter. Expression of molecules was studied using qPCR, Western blot and IHC. The link between RASSF1A and Hippo pathway was studied using Spearman's correlation in patients and validated by overexpressing RASSF1A in HT1376 cells and its effect on Hippo pathway was observed using qPCR and Western blot. Further therapeutic potential of this link was studied using MTT and PI assays. The expression of RASSF1A was lower, whereas the expression of YAP, CTGF and CYR61 was higher. The expression of RASSF1A protein gradually decreased, while the expression of YAP, CTGF and CYR61 increased with severity of disease. Based on Spearman's correlation, RASSF1A showed a negative correlation with YAP, CTGF and CYR61. YAP showed a positive correlation with CTGF and CYR61. To validate this link, RASSF1A was overexpressed in HT1376 cells. Overexpressed RASSF1A activated Hippo pathway, followed by a decrease in CTGF and CYR61 at mRNA, and enhanced cytotoxicity to chemotherapeutic drugs. This study finds a previously unrecognized role of RASSF1A in the regulation of CTGF and CYR61 through mediation of Hippo pathway in UBC and supports the significance of this link as a potential therapeutic target for UBC.

Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer.

PURPOSE: The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. MATERIALS AND METHODS: This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. RESULTS: Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p<0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis [area under ROC (AUROC) (±SD) was 0.873±0.061, p<0.001]. CONCLUSION: The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.

Association of Monoamine Oxidase A with Tumor Burden and Castration Resistance in Prostate Cancer.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A comparative analysis of various surgical approaches of nephron-sparing surgery and correlation of histopathological grade with RENAL nephrometry score in renal cell carcinoma.

Background: Nephron-sparing surgery (NSS) is the standard of care for small renal masses whenever feasible. This study aims to evaluate the perioperative outcomes of NSS performed by open (open partial nephrectomy [OPN]) or laparoscopic (laparoscopic PN [LPN]) or robotic (robotic PN [RPN]) approach over the past 6 years and to study the correlation of histopathological grade of renal cell carcinoma with the RENAL score. Materials and Methods: A retrospective analysis of prospectively collected data of all patients who underwent NSS was done. Results: A total of 135 patients underwent NSS. The mean tumour size was 4.4 cm. About 61 patients underwent OPN, 24 had LPN and 50 had RPN. Although tumour size was larger in OPN group (P = 0.01), tumour complexity based on the RENAL score was similar in OPN and RPN groups (P = 0.15). The OPN group had shorter operative time (P = 0.008) but more blood loss (P = 0.001) and length of hospital stay (P = 0.049) as compared to LPN or RPN group. Maximum radiological diameter of tumour (P = 0.017) appeared to be a significant predictor of operative time, while the open surgical approach (P = 0.003) and tumour stage (P = 0.044) were found to be significant predictors of blood loss. Hilar clamping time was similar in OPN and RPN groups (P = 0.054) but higher in LPN group (P = 0.01). However, post-operative decline in renal function (estimated glomerular filtration rate) (P = 0.08) and margin status were comparable among the three groups. The most common histopathology was clear cell carcinoma (70%), and RENAL score was identified as a significant predictor of histopathological grade of tumour (P = 0.008). Conclusion: Open, laparoscopic and robotic approaches to PN provide similar patient outcomes. OPN was usually preferred for larger tumours. The post-operative decline in renal functions and complications were comparable among the three approaches. RENAL score correlated significantly with histopathological grade and hence could help in predicting tumour behaviour pre-operatively.

Randomized controlled trial to compare outcomes with and without the enhanced recovery after surgery protocol in patients undergoing radical cystectomy.

INTRODUCTION: Very few randomized controlled trials are available globally to support routine use of enhanced recovery after surgery (ERAS) protocol after radical cystectomy (RC), and none so far has been conducted in the Indian subcontinent. The aim of the present study was to evaluate hospital stay and 30-day perioperative outcomes following RC with the implementation of the ERAS protocol. MATERIALS AND METHODS: Fifty-four patients undergoing open RC were randomized to ERAS versus conventional surgical care (CSC) at our center from April 2017 to May 2018. Key interventions included avoidance of mechanical bowel preparation, early nasogastric tube removal, early enteral feeding, and early obligatory ambulation. Follow-up was done till 30-day postoperatively or till discharge, whichever longer. RESULTS: Twenty-seven patients in each group were analyzed. The demographic profile of the groups was similar. Length of stay in each group (8 days [5-57] ERAS vs. 9 days [5-31] CSC group, P = 0.390) was similar, with time to recovery of bowel function being significantly less in ERAS group (12 h [12-108] vs. 36 h [12-60] for bowel sounds [P = 0.001], 48 h [12-108] vs. 72 h [36-156] for passage of flatus [P = 0.001], and 84 h [36-180] vs. 96 [60-156] for passage of stools [P = 0.013]). Perioperative complication rate (12 patients (44.4%) vs. 14 (51.9%), P = 0.786) was similar. CONCLUSIONS: ERAS protocol leads to faster bowel recovery compared to conventional care in patients undergoing open RC but fails to demonstrate a shorter length of stay and lower complication rate.

BK polyomavirus and urothelial carcinoma: Experience at a tertiary care centre in India with review of literature.

INTRODUCTION: BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma. MATERIAL AND METHODS: Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal). RESULTS: Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining. CONCLUSIONS: This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.

Prognostic stratification of muscle invasive urothelial carcinomas using limited immunohistochemical panel of Gata3 and cytokeratins 5/6, 14 and 20.

BACKGROUND: Genomic studies have delineated distinct molecular subgroups of urothelial carcinomas whose prognostic impact extends beyond traditional stage and grade groupings. The 'basal' subgroup shows increased gene expression levels of KRT5, KRT6, and KRT14 and low expression levels of GATA binding protein 3, and is associated with an extremely poor outcome. Identification of this subset is necessary for improved patient management and research on targeted therapies. We aimed to assess the prognostic utility of immunohistochemistry (IHC) for basal markers: cytokeratin 5/6 (CK5/6) and 14 (CK14), and luminal markers: cytokeratin 20 (CK20) and Gata3 in muscle invasive urothelial carcinomas (MIBC). MATERIALS AND METHODS: Study was of retrospective design (2014-2017). All chemotherapy naïve patients of MIBC undergoing radical cystectomy were included. IHC was performed on formalin fixed paraffin-embedded whole tumor sections. RESULTS: Among 40 cases of MIBC included, 45% (18/40) were positive for one or both basal markers, 37.5% (15/40) were positive for one or both luminal markers, while 15% (6/40) were positive for both basal and luminal markers. One case did not express any of the four markers. MIBCs expressing only basal markers presented at an advanced stage with frequent squamous differentiation and showed a trend towards shorter overall survival. Gata3+ MIBCs showed the best outcome irrespective of expression of other markers, while CK14+/Gata3- MIBCs were associated with worst outcomes. Gata3-/CK14- MIBCs showed intermediate survival outcomes. CK5/6, CK20 and p53 expression did not significantly correlate with outcome. CONCLUSION: IHC for Gata-3 and CK14 stratified MIBC into distinct prognostic subsets.

Decitabine augments cytotoxicity of cisplatin and doxorubicin to bladder cancer cells by activating hippo pathway through RASSF1A.

Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were treated with decitabine and its effect on RASSF1A expression, hippo pathway molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was observed. Effect of decitabine pretreatment on sensitivity of bladder cancer cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads to restoration of RASSF1A, activation of hippo pathway followed by decreased expression of its oncogenic downstream targets (CTGF & CYR61). Further pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to bladder cancer cells.