Spatial assessment and chemical characterization of degraded (salt-affected) soils at post-reclamation stage of the Indo-Gangetic Plain in Haryana State.

Dynamics of soil salinity and sodicity is a common feature driven by anthropogenic causes such as soil reclamation, the effect of extreme climate events, disturbed salt, and water balance in irrigated areas that are devoid of any good quality groundwater source and adequate natural surface drainage condition in a semiarid climatic region. Periodic soil salinity assessment is therefore vital to know the current soil salinity status, plan reclamation, and/or management strategies for sustained agricultural growth and livelihood security. Temporal studies using Indian Remote Sensing (IRS) LISS III data, at pre- (1997) and post-reclamation (2017) stages have indicated spatial changes as reclaimed areas (~ 35%) and dynamics of soil salinity as increased areas (~ 61%) under irrigation across the Gangetic plain of Haryana State. The prominent areas of reclaimed sodic soil soils were located in the old alluvial plain which covered Panipat (12.32%), Karnal (6.01%), and Jind (5.9%) districts. Based on pH, ECe, and ESP values, these were classified as slight (Sso1, 8.75%), moderate (Sso2, 24.73%), and strong (Sso3, 18.20%) sodic soils, respectively. Significant salinity-inflictions (emerging areas) were identified at low-lying, poorly drained, irrigated soils in south and central Haryana that cover Jhajjar (13.99%), Sirsa (11.06%), Hisar (10.15%), Rohtak (8.73%), Bhiwani (6.43%), Palwal (4.31%), and Rewari (3.01%) districts. Slight (Ssa1, 16.82%), and moderate (Ssa2, 22.13%), categories are dominant soils, respectively. Among the landforms, significant areas (28.24%) were identified in the old alluvial plain with sand dunes (OAPSD), aeo-fluvial plain (AFP, 8.6%), and fluvio-aeolian plain (FAP, 6.0%), respectively. Dominant areas of reclaimed soils (14.4%) were identified in OAPSD. The soil analysis data indicated that these soil are moderate to strongly sodic (pH 8.7-11.0) and saline (ECe 4-26 dS m-1). The reclaimed sodic soils showed prominent improvement in soil pH and sodicity levels (pH 8.3-9.2) at 0-15 cm depth and are commonly located in the Ghaggar and Yamuna river plains. Poor quality groundwater with high Residual Sodium Carbonate (RSC) was dominant at selected locations under the arid and semiarid climate. The database can also be used as a reference database for further monitoring of soil salinity status particularly in the irrigated regions. Currently, it is also used as a primary database for harmonization, monitoring, and reconciling of similar soils of the world under the Global Soil Partnership projects.

Metabolic evaluation of first-time uncomplicated renal stone formers: A prospective study.

Background: Nephrolithiasis is a global health problem. The recurrence rate after the first stone clearance is approximately 50% at 5 years. Metabolic abnormalities are an important factor responsible for stone recurrence. Our prevalidated study aimed to evaluate metabolic abnormalities associated with first-time uncomplicated renal stone formers (FTURSF). Materials and methods: In this prospective, exploratory, time-bound, descriptive study, 30 first-time renal stone formers were evaluated for metabolic abnormalities. High-risk stone formers were excluded from the study. Data were collected in a predefined proforma, transferred to an Excel sheet, and analyzed using the Statistical Package for Social Sciences 20 and Epi Info 7. Fisher exact test, Mann-Whitney U test, paired t test, and Pearson correlation coefficient were used for statistical analyses. Results: The mean age of the participants was 35.57 ± 11.07 years, with a male-to-female ratio of 1.72. The most common abnormality was a 24-hour urine volume of <2.5 L in 73.33% of the participants. One or more metabolic abnormalities were detected in 76.67% of the participants. Other common metabolic abnormalities detected were hypocitraturia (60%), hypercalciuria (16.67%), hyperoxaluria (13.33%), and hyperuricosuria (3.33%). Parathyroid adenoma was detected in one participant (3.33%). Conclusions: Our study documented significant metabolic abnormalities in FTURSF. Therefore, a simplified metabolic evaluation protocol should be adopted while evaluating FTURSF. Detection of an underlying metabolic abnormality would enable the early institution of preventive measures to reduce stone recurrence and related complications.

Urodynamics in the evaluation of lower urinary tract symptoms in young adult men: A systematic review.

Introduction: This review aims to systematically evaluate the available evidence on the different urodynamic diagnoses of lower urinary tract symptoms (LUTS) in young adult men aged 18-50 years and to summarize the various urodynamic parameters based on these diagnoses. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement and the search was performed in PubMed, Embase, and Cochrane library from inception till September 2021. A total of 295 records were identified using a combination of keywords such as LUTS, urodynamics (UDS), and young males. The review was registered in PROSPERO (CRD42021214045). Results: All the ten studies, which were included in this analysis, categorised the patients into either of the four primary diagnoses after the UDS - primary bladder neck obstruction (PBNO), dysfunctional voiding, detrusor underactivity (DU), or detrusor overactivity. Five of these studies used the conventional UDS, and in the other five a video UDS was performed. The most common abnormality on the conventional UDS was DU with a pooled estimate of 0.24 (95% confidence interval [CI] - 0.104-0.463, I2-95.35, (τ2-1.07). The most common abnormality on the video UDS was PBNO with a pooled estimate of 0.49 (95% CI - 0.413-0.580, I2-66.59, 2-0.09). The point estimates of various UDS parameters were also recorded. Conclusion: A urodynamic diagnosis was possible in 79% and 98% of the young men who underwent a conventional UDS or a video UDS, respectively. However, the men subjected to the conventional UDS and the video UDS had significant differences in their primary urodynamic diagnostic label. These results will help to plan future trials for the evaluation and management of LUTS in young men.

Interruption of BCG Therapy for NMIBC During COVID-19 Crisis, Dilemma in Its Continuation: a Review of Available Evidence and Suggested Management Strategies.

The COVID-19 disease, caused by SARS-CoV-2 virus, has been one of the worst pandemics ever to hit the human mankind. Undoubtedly the start of the second wave of COVID-19 has literally ripped apart the hearts of millions of people. Cancer patients have been left of the beaten track to their fate, with no access to treatments. Intravesical BCG instillation is the standard of care for patients with non-muscle invasive bladder cancer (NMIBC). Several patients were in the middle of their treatment regimen when this pandemic struck. As slowly the word is recuperating from concussion effect of this pandemic and routine health services are being restored, uro-oncologist will face a unique scenario with respect to intravesical BCG therapy i.e., whether to restart the course of BCG therapy or to continue course from where it was interrupted. There are no studies in literature to directly answer this peculiar question and to resolve this dilemma. So, we in this review article propose to explore the literature for the most appropriate therapeutic regimen for these patients with interruption of intravesical BCG therapy. We plan to divide the patients with interruption to BCG therapy into the following three groups:Group 1: Patients who had interruption during the induction period.Group 2: Patients who completed the induction course but maintenance course could not be started.Group 3: Patients who had interruption during maintenance phase of BCG therapy. We will compile the recent recommendations by NCCN, AUA, and EAU for the administration of intravesical BCG in non-muscle invasive bladder cancer. We herein want to review the literature to propose the most appropriate strategy, its safety profile for these subsets of patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01742-8.

Soil degradations in the IGP of central Haryana, India-a spatial assessment for reclamation and management.

Natural and anthropogenic processes are primary drivers for soil degradations in the Gangetic plain of India. Indian Remote Sensing (IRS) data was used to assess soil degradations and study spatial changes comparing with the legacy datasets. Based on the nature, extent, and degrees of limitations, these soils were evaluated to suggest suitable reclamation and management options. Typical strong signature (white tones) from a barren highly salinized soil (P3, P6, P9, P11, and P15) and higher energy absorption (blue-black tones) from a permanent waterlogged surface (P13, P14, P10) in the irrigated areas have favored delineation of salt-affected, strong, and permanent waterlogged areas. Moderate and slightly salt-affected soils (P1, P2, P4, P5, P7, P8, and P12) and the areas with high water table depths (P13 and P14) have shown mixed spectral signatures for associations of soil, water, and crops and were mapped using ground truth and soil chemical analysis data. Irrigation with poor quality ground water (RSC: 1.2 to 12.3 me L-1) has prompted developing salinity and sodicity in P2, P5, and P11, while irrigation in poorly drained areas caused appearance of waterlogging (WTD < 1.5 m) and salinization (P3, P5, P7, P9, P13, P14). The gypsum application and sub-surface drainage (SSD) techniques have enhanced soil reclamation by (i) neutralizing CO32 - and HCO3 - in P12 (pH 9.2, ESP 24) and (ii) controlling soil salinity (EC 3.0 dS m-1) and waterlogging (WTD > 1.5 m) in P14. Soils with CaCO3 layers at shallow depth in P3 (0.7-4.2%), P6 (1.2-7.1%), P9 (8-16%), P11 (4-15%), and P13 (0.9-9.4%) were managed using forest plantations. Ground water with high SAR in T1 to T7 can be applied for agriculture using mixing or cyclic mode. Water with high RSC in T4, T5, T7, T8, T9, and T10 needs treatment with gypsum. A significant area (~ 24.87%) of salt-affected soils was reclaimed since 1971. Prominent changes (3.27 to 17.71%) were shown in Panipat and Karnal districts. Small areas of brick kiln (P11), industrial effluent (P10), riverine sand, partially stabilized dunes, and mining have appeared due to anthropogenic activities.

Small contracted bladders posing bigger problems: Etiology, presentation, and management and a short review of literature.

The purpose of this study was to assess various etiologies, diagnosis and management. This rare entity is a neglected condition which should always be under clinical suspicion by broad speciality of practitioners for early treatment. Retrospective data collected from 2018 to 2021 in the All India Institute of Medical Sciences Rishikesh was used. All patients diagnosed with the small contracted bladder in the given period were included. The primary outcome of the study was to find out the common causes, early tests used for diagnosis and management done in the patients of small contracted bladder attending this tertiary care centre. Between 2018 and 2021, a total of 12 patients were diagnosed to have small capacity bladder (SCB). The most common symptom was frequency (75%). On cystoscopy, 33.33% (n = 4) had less than 50 ml and 66.66% (n = 8) had 50-100 ml bladder capacity respectively. 37.5% (n = 3) were diagnosed by urine AFB culture, 62.5% (n = 5) were diagnosed by urine for PCR, 62.5% (n = 5) were diagnosed by radiological investigations. Eight patients (66.66%) underwent surgical treatment in cases diagnosed as tuberculosis like augmentation cystoplasty and supra-trigonal cystectomy. Other rare causes found were eosinophilic cystitis, radiation induced contracture and BCG induced contracture. Small capacity bladder is an unusual condition, with still dilemma on the definition of small capacity and only few literature mentioning the causes, diagnosis and treatment. Even though tuberculosis is a common cause of SCB, still rare causes should always be kept in mind for relieving patient symptoms at the earliest.

Efficacy and Safety of Percutaneous Nephrolithotomy in Patients with Chronic Kidney Disease: Outcomes from a Tertiary Care Center.

Background: The management of renal stone disease in the presence of chronic kidney disease (CKD) is a challenging scenario, both in terms of surgical safety and perioperative outcomes. The aim of the present study is to study the efficacy, safety, and outcomes of percutaneous nephrolithotomy (PCNL) in patients with CKD. Materials and Methods: A prospective study was conducted including adult patients with renal stone disease and a creatinine clearance of <90 mL/min (Stage 2 CKD or more) who underwent PCNL. Pre- and postoperative serum creatinine and glomerular filtration rates (GFRs) were compared. Patients were divided into CKD Stages 1 to 5 having creatinine clearance >90 mL/min, 60 to 90 mL/min, 30 to 60 mL/min, 15 to 30 mL/min, and <15 mL/min, respectively. Based on up migration or down migration of CKD stages, patients were classified as improved, deteriorated, or stable. Perioperative complications and outcomes were also compared. Results: A total of 185 patients with CKD Stage ≤2 underwent PCNL. The mean age of the patients was 43.24 ± 14.32 years. The mean preoperative estimated glomerular filtration rate (eGFR) was 62.88 ± 23.42 mL/min/1.73 m2. Preoperative CKD stage distribution was as follows: Stage 2 to 121 (65.4%), Stage 3 to 34 (18.4%), Stage 4 to 24 (13%), and Stage 5 to 6 (3.2%). On last follow-up of patients, the mean creatinine was 1.07 ± 0.65 mg/dL and the mean eGFR was 82.75 ± 31.22 mL/min/1.73 m2. The median change in creatinine and mean change in GFR were 0.23 (0.16-0.27) g/dL and 19.87 ± 19.77 mL/min/1.73 m2, respectively. Improvement in kidney function with a stage down migration was seen in 115 cases (62.2%), slight improvement with no change in stage in 69 cases (37.3%), and deterioration of CKD stage was present in one case (0.5%). Conclusion: PCNL is associated with favorable functional outcomes in CKD patients including severe CKD (Stages 4 and 5). Improvement or stabilization of CKD stage was seen in 99.5% of patients post-PCNL.

'Pee'BuSt Trial: A single-centre prospective randomized study comparing functional and anatomic outcomes after augmentation urethroplasty with penile skin graft versus buccal mucosa graft for anterior urethral stricture disease.

PURPOSE: To assess the surgical outcomes of augmentation urethroplasty (AU) using penile skin graft (PSG) compared to buccal mucosa graft (BMG) in anterior urethral stricture disease. METHOD: Between January 2018 and January 2019, 100 patients with anterior urethral stricture planned for AU were randomized into PSG or BMG arms (CTRI/2018/07/015028). Anatomic and functional variables were compared pre-operatively and post-operatively. Primary outcome was success rate at 18 months and it was defined if any of the three criteria were met, i.e. either maximum urinary flow (Qmax) > 15 ml/s or urethral calibration of 16 French or ability to traverse the repair with 17 French cystoscope. Secondary outcomes were functional parameters such as International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), and Urethral Stricture Surgery-Patient Related Outcome Measure (USS-PROM). RESULTS: Pre-operative variables were comparable between both the arms. Median duration of follow-up was 22 months (18-24 months). At 18 months, the success rates of AU with PSG and BMG were comparable (89% v/s 91%; p = 0.70, 95% CI-0.33 to 5.21). The improvements in Qmax (p = 0.06), IPSS (p = 0.43) and USS-PROM (p = 0.49) were comparable between the two arms. There was no statistically significant difference in the IIEF-Erectile domain (p = 0.07), IIEF-Orgasmic domain (p = 0.11) and MSHQ-EJD (p = 0.20) following AU at 18 months. Clavien-Dindo grade I complications were 12.7% in PSG and 16.7% in BMG. CONCLUSION: This study provides level 1 evidence of no statistical significant difference in outcomes of AU using BMG or PSG.

A Clinicopathological Correlation of Bladder Cancer in Young and Old Patients: Our Experience and Review of Literature.

To compare the clinical, cystoscopic, and pathological characteristics of bladder cancer in patients younger than 40 years of age and those of patients older than 40 years of age. We conducted a prospective observational study at our department from September 2019 to February 2021 to compare the clinico-pathological characteristics of young and old patients with biopsy proven bladder cancer after a transurethral resection of bladder tumour. The patients were managed according to standard guidelines. Two hundred sixty-eight patients of bladder cancer were included in the analysis. Out of these, 58 patients were < 40 years of age and 210 were > 40 years. The mean age of two groups were 31.43 ± 6.30 vs 59.08 ± 9.87 years. With respect to tumour grade, 36.2% (versus 17.6%) of young patients had low grade tumour, and 58.6% had high-grade tumour (versus 82.4%). In the young population, 63.8% patients had NMIBC (versus 61.9%) and 36.2% had MIBC (versus 38.1%). Even in the NMIBC group, a large majority of young patients had high-risk disease (51.4%). The incidence of bladder cancer is on the rise in the northern belt of India, especially in the younger age group. High exposure to smoke and heavy metals in drinking water/occupation are the major risk factors. Majority of young patients aged < 40 years had a high-grade disease on presentation and a large subset had muscle invasive bladder cancer, contrary to previously reported studies.

Laser epilation of luminal hair following skin graft urethroplasty for hypospadias: the hair snare.

A 66-year-old man, who underwent urethral reconstruction using skin grafts for hypospadias five decades earlier as a 13-year-old child, presented with burning micturition and recurrent UTI. A retrograde urethrogram along with micturating cystourethrogram revealed a bulbar urethral stricture and broad neck distal penile urethral diverticulum. On a cystourethroscopic examination, a urethral diverticulum was seen just proximal to the hypospadiac external urethral meatus with 12-15 hair follicles inside the diverticulum and a 1 cm long mid-bulbar stricture. Visual internal urethrotomy for the bulbar stricture, a diverticular neck incision, laser epilation and hair follicle photocoagulation was performed using a 30 W Ho:YAG laser. The depilated hair tufts were extracted. The process was repeated again in 6 months due to recurrent symptoms. A patent urethra with a wide open diverticulum without any residual hair follicles was confirmed. No perioperative complications noted and the patient is doing well on 1 month of follow-up.

Mixed Mott-Hubbard and charge transfer nature of 4H-SrMnO3thin film on Si (100).

Room temperature electronic structure of polycrystalline 4H-SrMnO3thin film grown on Si (100) substrate has been studied using resonance photo emission spectroscopy and soft x-ray absorption spectroscopy measurements. Presence of charge transfer screen Mn 3dnLfinal state along with the 3dn-1final state at the valence band edge of 4H-SrMnO3thin film confirms that the ground state is strongly mixed between Mn 3dand O 2pstates. The estimated equivalent values of on-site Coulomb interaction energy (U) and O 2pto Mn 3d- charge transfer energy (Δ) (U≈ Δ ≈ 4.8 eV) from the combination of occupied and unoccupied spectra further confirm the intermediate Mott-Hubbard and charge transfer insulator nature of 4H-SrMnO3film. Despite having similar Mn 4+ valence state in 4H-SrMnO3and cubic SrMnO3, 4H phase is observed to reveal much higher band gap ∼1.5 eV than the cubic phase (0.3 eV), which arises due to different MnO6octahedra environment.

Neoadjuvant Therapy for Cisplatin Ineligible Muscle Invasive Bladder Cancer Patients: A Review of Available Evidence.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for muscle invasive non-metastatic bladder cancer patients. While cisplatin based neoadjuvant chemotherapy has been recommended, systemic therapy in a neoadjuvant setting for cisplatin ineligible patients still needs to be addressed. Various strategies like split dosing cisplatin chemotherapy, carboplatin based chemotherapy and taxanes based chemotherapy have been tried as neoadjuvant therapy for cisplatin ineligible patients. Immunotherapy is a promising tool in this regard with a need for the development of predictive and prognostic biomarkers which can bring out the true potential of these immunotherapeutic agents.

A nationwide cross-sectional study to assess the impact of COVID-19 on surgical residency programs in India.

BACKGROUND: The COVID-19 pandemic with its plenitude of hardships has been a challenge for residents in training. Besides the fear of contracting the disease, the complete reconfiguration of hospital services has severely affected the surgical residency programs across India. The current study highlights the lacunae that have arisen in the residency programs and design appropriate solutions to reframe the remaining part of the surgical training. MATERIALS AND METHODS: The present study is an observational study based on a questionnaire survey done in November 2020 aimed at gauging the mood and perspective of residents across India pursuing surgical residency programs on how the pandemic has impacted various domains of their residency namely surgical training, clinical skills, research, academic curriculum, and mental health. The analysis was performed using an Internet-based program. RESULTS: Seventy-eight percent of residents felt that they have lost crucial months of surgical training. Impact on clinical skills was reported by 73.9% of residents. Almost half of the residents (49.1%) believed that there has been a definite increase in research activities and 81.7% believed that the academic curriculum was affected during the past 6 months. Furthermore, 86% of respondents admitted to have had a profound impact on their mental health as a result of the pandemic. CONCLUSION: Formulating reform policies in the current residency programs is paramount to train the current and future generation of surgeons. Whereas personal safety and wellness of the residents is paramount during these times, residency training via digital medical education and various other innovative ways needs to continue.

Does Miniaturization Actually Decrease Bleeding After Percutaneous Nephrolithotomy? A Single-Center Randomized Trial.

Introduction: Miniaturization of percutaneous nephrolithotomy (mPCNL) was proposed to decrease postoperative bleeding, as there is decreased parenchymal injury compared with standard percutaneous nephrolithotomy (SPCNL). Published randomized controlled trials (RCTs) evaluating bleeding after mPCNL have shown conflicting results. Hence, the evidence to say that mPCNL offers less postoperative bleeding is not robust. Materials and Methods: Prospective RCT was done by comparing mPCNL and SPCNL for treatment of renal stones of size 1 to 3 cm. Patients with active urinary tract infection, renal malformation, uncorrected coagulopathy, and raised serum creatinine (>1.5 mg/dL) were excluded. Blood loss was evaluated by measuring fall in hemoglobin and hematocrit on postoperative day 1. Postoperative pain was evaluated by visual analogue scale (VAS) score at 6, 24, and 48 hours. Results: A total of 60 patients (30 in each arm) were enrolled during the study period. All the baseline preoperative variables were comparable in both the groups. The SPCNL group had a significantly higher drop in hematocrit level as compared with mPCNL (4.6 ± 3.1% vs 3.1 ± 2.1%, p = 0.02). The mean fall in hemoglobin was higher in SPCNL as compared with mPCNL (1.61 ± 0.9 gm% vs 1.21 ± 0.7 gm%, p = 0.07), but it was not significant. Blood transfusion (BT) rate was comparable in both the groups (one patient in each group). The mPCNL group had significantly less VAS scores at 6 hours (3.27 ± 1.20 vs 4.40 ± 1.52, p = 0.002) and 24 hours (2.10 ± 0.54 vs 2.83 ± 1.05, p = 0.001) after surgery. Postoperative complications and hospital stay were comparable in both the arms. Conclusion: mPCNL is associated with less postoperative bleeding and pain than SPCNL. However, the small tract size does not prevent against the clinically significant bleeding requiring BT.

Synchronous retroperitoneal Castleman's disease with clear cell renal cell carcinoma.

Castleman's disease is a rare non-clonal lymphoproliferative disorder and known to be associated with a number of disorders such as polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome, Kaposi sarcoma, paraneoplastic pemphigus and plasma cell dyscrasias. The association of Castleman's disease with epithelial malignancy is not clear and limited to few case reports. We describe a case of synchronous Castleman's disease with renal cell carcinoma in a 53-year-old woman. She presented with right abdominal lump with feeling of heaviness. She also presented with vague discomfort in left hypochondrium for 15 years. The CT imaging of abdomen revealed two masses-one in right kidney and another in left anterior pararenal space of retroperitoneum. The patient underwent right radical nephrectomy with excision of left retroperitoneal mass. Histological examination revealed clear cell renal cell carcinoma and Castleman's disease, respectively. Role of interleukin-6 has been postulated as an important factor in association of Castleman's disease and epithelial malignancy.

IgG4-related Retroperitoneal Fibrosis: An Emerging Masquerader With a Sinister Presentation.

OBJECTIVE: Retroperitoneal fibrosis (RPF) is a rare proliferative fibro-inflammatory disease involving the soft tissues of the retroperitoneum. IgG4 related retroperitoneal fibrosis is an emerging entity which needs to be distinguished from idiopathic RPF. We describe a clinical case of IgG4 related RPF highlighting the importance of clinching this diagnosis. METHODS: A 70 year old female was referred to the outpatient department of our institute with complaints of fatigue, bilateral flank pain and loss of appetite for the past 1 month. The CT and PET scan demonstrated a uniformly enhancing bulky retroperitoneal mass causing bilateral hydroureteronephrosis. The biopsy from the mass lesion revealed IgG4 related disease. The patient was started on corticosteroids after percutaneous nephrostomy placement. RESULTS: Three months post induction of therapy, repeat PET-CT shows resolution of the mass with no FDG avid lesion. Serum IgG4 levels were reduced to normal (27 mg/dL) suggestive of response to treatment. The percutaneous nephrostomies were removed and the patient is doing well on maintenance dose of corticosteroids for her disease. CONCLUSION: The availability of serum IgG4 levels for monitoring treatment response and follow-up can curtail the repeated radiological imaging and associated contrast exposure as compared to idiopathic RPF. Secondly, the diagnosis of IgG4-related RPF shall alert the clinician to look out for extra-retroperitoneal diseases on follow up of this multi-organ disease.

Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels.

Background: Urothelial carcinoma is the most common malignancy of the bladder and is primarily considered as a disease of the elderly. Studies that address bladder tumor occurrence in young age groups are rare. Case Presentation: A 19-year-old male presented with a gross total painless hematuria. A histology after biopsy revealed a high-grade transitional cell carcinoma with lymph node metastasis. The patient succumbed to the disease on day 72 of the treatment. Here, we used whole-exome sequencing of a paired tumor-normal sample to identify the somatic mutations and the possible targets of treatment. Result: We predicted eight potential driver mutations (TP53 p.V157L, RB1 c.1498+1G>T, MED23 p.L1127P, CTNND1 p.S713C, NSD1 p.P2212A, MED17 p.G556V, DPYD p.Q814K, and SPEN p.S1078*). In addition, we predicted deleterious mutations in genes involved in the ion channels (CACNA1S p.E1581K, CACNG1 p.P71T, CACNG8 p.G404W, GRIN2B p.A1096T, KCNC1 p.G16V, KCNH4 p.E874K, KCNK9 p.R131S, P2RX7 p.A296D, and SCN8A p.R558H). Conclusions: Most likely, mutations in genes involved in ion channels may be responsible for the aggressive behavior of a tumor. Ion channels are the second largest class of drug targets, and may thus serve as a putative potential therapeutic target in advanced stage urothelial carcinoma.

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.