Diagnostic utility of α-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer

<p>Abstract</p> <p>Background</p> <p>To evaluate the diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK (34beta E12) in morphologically difficult prostate cancer.</p> <p>Methods</p> <p>A total of 1034 cases were reviewed and divided into benign (585) malignant (399) and suspicious (50). Immunohistochemistry with HMWCK and AMACR was done on the 50 suspicious cases along with controls.</p> <p>Results</p> <p>Forty nine suspicious cases were resolved by using both markers where as 1 case was resolved by further support with CD68. The original diagnosis was changed in 15 of 50 (30%) suspicious cases from benign to malignant, one case from benign to high grade PIN and in one case from malignant to benign. Change of diagnosis was seen in 17 of 50 (34%) suspicious cases with a significant p value of 0.002. The overall diagnosis was changed in 17 of 1034 cases (1.64%) of prostatic disease (p < 0.001).</p> <p>Conclusions</p> <p>A combination of HMWCK and AMACR is of great value in combating the morphologically suspicious cases and significantly increasing the diagnostic accuracy in prostate cancer. Although, in this study the sensitivity and specificity of HMWCK and AMACR were high, yet it should be used with caution, keeping in mind all their pitfalls and limitations.</p

Audit of Clinical Care Received by COVID-19 Patients Treated at a Tertiary Care Hospital of Nepal in 2021

Like the world over, Nepal was also hard hit by the second wave of COVID-19. We audited the clinical care provided to COVID-19 patients admitted from April to June 2021 in a tertiary care hospital of Nepal. This was a cohort study using routinely collected hospital data. There were 620 patients, and most (458, 74%) had severe illness. The majority (600, 97%) of the patients were eligible for admission as per national guidelines. Laboratory tests helping to predict the outcome of COVID-19, such as D-dimer and C-reactive protein, were missing in about 25% of patients. Nearly all (&gt;95%) patients with severe disease received corticosteroids, anticoagulants and oxygen. The use of remdesivir was low (22%). About 70% of the patients received antibiotics. Hospital exit outcomes of most (&gt;95%) patients with mild and moderate illness were favorable (alive and discharged). Among patients with severe illness, about 25% died and 4% were critically ill, needing further referral. This is the first study from Nepal to audit and document COVID-19 clinical care provision in a tertiary care hospital, thus filling the evidence gap in this area from resource-limited settings. Adherence to admission guidelines was excellent. Laboratory testing, access to essential drugs and data management needs to be improved

Metallothionein gene expression in renal cell carcinoma

Introduction: Metallothioneins (MTs) are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1) the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2) apoptosis and (3) the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC). No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR) analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01) in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05), while no change was observed in high-grade tumor (grade III and IV) in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis

Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study

Introduction: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. Methods: Men ≥45 years of age, with an International Prostate Symptom Score (IPSS) ≥8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. Results: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P 0.05). Significant period effect was observed (P < 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. Conclusion: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa

Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: a systematic review and meta-analysis

Introduction: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings. Methods: Extensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis. Results: Ten nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1-21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3-14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9-27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5-2.9 vs. 2.0-2.7 months and 7.9-18.2 vs. 15.9 months) and second-line chemotherapy (3.3-4.0 months and 7.4-8 months). Odds of achieving ORR was 0.10 (95% CI 0.03-0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19-0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible. Conclusions: PD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care

Utility of restage transurethral resection of bladder tumor

Introduction: Transurethral resection of bladder tumor (TURBT) aims at complete resection of all the visible tumors. Existing guidelines recommend restage TURBT in all patients with T1 and high-grade tumors, to avoid under-staging. However, restage TURBT may not be plausible/feasible at all the times. This study was performed with an aim to better define the utility of restage TURBT in a tertiary care hospital of India. Methods: Patients with high grade/T1 tumors at the first TURBT were prospectively enrolled. Their demographic profile, previous cystoscopic findings, and histological reports were recorded. The primary objective was to assess the tumor detection and stage up-migration rates at restage TURBT. The secondary objectives was to identify factors predicting presence of tumor at restage TURBT. Patients were followed up to detect recurrence and progression for a minimum of 3 months. Results: Of 128 prospective patients' enrolled, 29 patients were lost to follow-up and 11 patients did not undergo restage. A total of eighty-eight patients underwent restage TURBT of which twenty-eight patients (31.8%) had tumor at their second TURBT with five of these patients being upstaged to T2. The risk of having a tumor at restage was significantly higher in patients with solid tumors (56.2% vs. 26.4%, P = 0.02, 95% confidence interval: 0.035–0.024) but was independent of the tumor size (P = 0.472), number of growths (P = 0.267), grade of tumor (P = 0.441), presence or absence of muscle at the initial TURBT (P = 0.371) and place of initial TURBT (P = 0.289). There was a significant difference in the recurrence and progression rates in patients who had tumor at restage as compared to those who did not (recurrence; 33.3% and 23.8%, P = 0.022, respectively vs. progression; 11.1% and 3.7% respectively, P = 0.07; mean follow-up = 10.8 months). Conclusions: We conclude that restage TURBT is necessary in patients with solid looking tumors and the presence of tumor at restage confers a higher risk of recurrence and progression

Perioperative outcomes of minimally invasive versus open radical cystectomy: A single-center experience

Introduction: Open radical cystectomy (RC) is associated with significant morbidity and the role of minimally invasive surgery (MIS) in reducing morbidity of RC is controversial A direct comparison of various surgical modalities on perioperative outcomes is lacking in the Indian literature. We evaluated outcomes of minimally invasive (robotic and laparoscopic) versus open RC with pelvic lymph node dissection (PLND) performed at our institute from 2014 to 2016. Methods: Eighty-three patients of RC with PLND were prospectively analyzed from December 2014 to February 2016. All patients of muscle invasive urothelial cancer of the bladder undergoing RC (open or MIS) were included in the study. Based on patients preference they were assigned to one of the three groups (Open RC, robot-assisted RC, or laparoscopic RC). Their demographic profile, preoperative disease stage, operative data like operative time, blood loss, intraoperative complications, histopathological data like pathological stage, lymph-node yield etc., postoperative complications if any and total duration of stay were recorded. These data of laparoscopic, open, and robotic cystectomies were compared in terms of various demographic, histopathologic parameters and perioperative outcomes. Results: Twenty-nine patients (34.93%) underwent minimally invasive RC with PLND (5 laparoscopic and 24 robotic). The median age of patients was 58 years. Mean number of lymph nodes removed was 22.5 ± 14.6. The total number of lymph nodes removed in laparoscopic surgery was 104 with a yield of 20.6 per patient, in robotic surgery were 627 with a yield of 26.1 per patient, and in open surgery were 1119 with a yield of 20.7 per patient (P = 0.004). Clavien-Dindo Grade 2 and 3 complications were seen in 37.5% of robotic, 60% of laparoscopic, and 55.54% of open RC. Average blood loss and operative time in laparoscopic, robotic, and open RC were 511.53 ± 311.02 ml, 552.08 ± 267.63 ml, and 512.05 ± 213.9 ml and 8.23 ± 1.36 h (hrs), 7.53 ± 1.92 h, and 5.85 ± 1.76 h, respectively (P = 0.68 and <0.001, respectively). Conclusions: MIS is associated with significantly longer operative time than open RC. Robotic RC has significantly higher lymph node yield than open or laparoscopic RC. Minimally invasive RC is equivalent to open surgery in terms of perioperative morbidity, mortality, and blood loss

Revisiting the clinical trial history and regulatory mechanisms in Nepal in the context of COVID-19 pandemic

Presence of Nepal in global clinical trials has been visibly negligible despite the history of conducting large scaled randomized controlled trial on Hepatitis E vaccine decades ago. Majority of the problem is attributed to the lack of collaborative work, financial and human resource constrains. COVID-19 pandemics seems to have triggered urgency among the authorities of Nepal leading to a substantial increase in the number of clinical trials in collaboration with national and international organizations/institutions. Immediately after detection of the first COVID-19 case on 13 January 2020, the Ethical Review Board (ERB) of NHRC received several research proposals, subsequently leading to the approval of the first clinical trial for COVID-19 on 01 July 2020 to investigate potential of traditional Ayurveda based medicine for COVID treatment. Soon, number of other clinical trial proposals received approval and implemented in the country, however budgetary allocation from the Government of Nepal (GON) was prioritized for COVID-19 outrage management and vaccination coverage only. Collaborations with various international institutions played a significant role in the successful implementation of large-scale clinical trials in the country and further laid the path for future. In this review paper we present the recent developments in clinical trials in Nepal, budgetary allocation from the government and the mechanisms in place for regulation of clinical research in the country along with challenges and way forward

Protocol-based perioperative antimicrobial prophylaxis in urologic surgeries: Feasibility and lessons learned

Introduction: Rational use of antibiotics and strict adherence to practice guidelines is essential to prevent antibiotic resistance. The best surgical prophylaxis protocol requires tailoring of the available guidelines in accordance to the local bacterial flora. We designed a protocol for surgical prophylaxis to check the rampant abuse of antibiotics in the department of urology and evaluated its feasibility. Materials and Methods: Patients admitted for elective major surgeries under a single unit of our department over a period of 5 months were included in the study. A protocol for antibiotic prophylaxis was designed based on the European Association of Urology guidelines and the local hospital antibiogram. Single-dose intravenous cefuroxime was administered to the patients undergoing clean and clean-contaminated surgeries. Extended protocols were formulated for contaminated surgeries. Postoperative course and complications were recorded. Effectiveness was defined as adherence to the protocol (without an addition or a change in antibiotic regimen) along with an uneventful postoperative course. Prospectively maintained data were analyzed using descriptive statistics. Results: Data of 277 patients were analyzed. The mean age was 48.37 ± 17.39 years and 27.1% had comorbidities. Majority of the surgeries were clean contaminated (81%), and 60.3% of the total were endoscopic. The protocol was effective in 89.5% of the patients (248/277). The failure rate was higher for the contaminated procedures (41.7%) (odds ratio – 6.43; confidence interval = 1.51–27.2, P < 0.001). Post-operative sepsis with or without shock was the commonest cause (16/29, 55.2%) of protocol failure. Fourteen out of the 16 patients who developed sepsis had undergone endourological surgeries. Conclusions: Protocol-based perioperative antibiotic prophylaxis in urological surgeries is feasible. Similar protocols should be developed and validated at other major centers to limit the unnecessary use of antibiotics and prevent the emergence of antibiotic resistance