Selina Bhattarai - Academia.edu (original) (raw)

Papers by Selina Bhattarai

European Journal of Surgical Oncology, 2021

OBJECTIVES To analyse the safety, technical feasibility, long-term renal function and oncological... more OBJECTIVES To analyse the safety, technical feasibility, long-term renal function and oncological outcome of multimodal technologies in image-guided ablation (IGA) for renal cancer in Von-Hippel-Lindau (VHL) patients, and to evaluate factors that may influence the outcome. METHODS Retrospective analysis of a prospective database of VHL patients who underwent IGA at a specialist centre. Patient's demographics, treatment energy, peri-operative outcome and oncological outcomes were recorded. Statistical analysis was performed to determine factors associated with complication and renal function reduction. The overall, 5 and 10-year cancer specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates were presented with Kaplan-Meier Curves. RESULTS From 2004 to 2021, 17 VHL patients (age 21-68.2) with a mean (±SD) RCC size of 2.06 ± 0.92 cm received IGA. Median (IQR) RCCs per patient was 3 (2-4) over the course of follow up. Fifty-four RCCs were treated using radiofrequency ablation (n = 11), cryoablation (n = 38) and irreversible electroporation (n = 8) in 50 sessions. Primary and overall technical success rate were 94.4% (51/54) and 98% (53/54). One CD-III complication with proximal ureteric injury. Five patients in seven treatment sessions experienced a >25% reduction of eGFR immediately post-IGA. All patients have preservation of renal function at a median follow-up of 79 (51-134) months. The 5 and 10-year CS, LRF and MF survival rates are 100%, 97.8% and 100%. Whilst, the 5 and 10-year overall survival rate are100% and 90%. CONCLUSION Multimodal IGA of de novo RCC for VHL patients is safe and has provided long term preservation of renal function and robust oncological durability.

OBJECTIVE: To test the hypothesis that the baseline clinico-pathological features of the men with... more OBJECTIVE: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409). PATIENTS AND METHODS: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models. RESULTS: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had ba...

Canadian Urological Association Journal, 2007

A 51-year-old man presented with a 2-year history of painless lump in the left hemiscrotum. Scrot... more A 51-year-old man presented with a 2-year history of painless lump in the left hemiscrotum. Scrotal examination demonstrated a 3-cm, firm-to-hard mass attached to the left spermatic cord. Scrotal ultrasound scan revealed a heterogeneous mass separate from the left testis and epididymis. An orchidectomy was recommended to the patient; however, he declined surgery and underwent excision biopsy of the lesion with preservation of the left testis. Histology suggested a leiomyosarcoma of the spermatic cord and positive margins. Following a normal staging CT scan, the patient was referred to the regional sarcoma clinic. He was treated with an orchidectomy. Microscopic examinations showed fibrosis in the spermatic cord and negative margins. The patient has been followed up for 12 months with CT scans and shows no signs of recurrence.

Modern Pathology, 2021

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypic... more Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19–80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Radiology Case Reports, 2020

A 69-year-old lady with 2 renal cell carcinomas, one sited at the upper pole of her solitary righ... more A 69-year-old lady with 2 renal cell carcinomas, one sited at the upper pole of her solitary right kidney, underwent percutaneous image-guided cryoablation and developed urinothorax as a complication. This was diagnosed from pleural fluid analysis and radiology imaging with computed tomography (CT). Management included image-guided chest drain and retrograde ureteric stent insertion to divert the urine from entering the pleural cavity. CT images demonstrated a fistula between the site of renal puncture and the pleural cavity, indicating that the cryoprobes traversed the diaphragm during the procedure. This case highlights urinothorax as an unusual complication of cryoablation of renal cell carcinoma. Prompt diagnosis by interventional radiologists is crucial to avert from this potentially life-threatening complication.

Radiology Case Reports, 2021

Clinical Oncology, 2016

ProtecT study group see acknowledgements Clinical Oncology: Original article 3215 words, 2 tables... more ProtecT study group see acknowledgements Clinical Oncology: Original article 3215 words, 2 tables, 3 figures, 39 references

BJU international, Jan 14, 2016

To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Can... more To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-...

BJU international, Jan 20, 2015

Penile preserving surgery is increasingly offered to men with localised penile cancer and surgica... more Penile preserving surgery is increasingly offered to men with localised penile cancer and surgical margins of less than 10 mm appear to offer excellent oncological control. Invasion of the tunica albuginea (TA) and the urethra are important factors in determining the feasibility of such surgery. We assessed the accuracy of magnetic resonance imaging (MRI) in predicting the invasion of the tunica albuginea and the urethra during the primary staging of penile Cancer. One hundred and four consecutive patients with clinical T1-T3 penile cancer had a penile MRI as a part of local staging protocol. An artificial erection was induced by injecting alprostadil (prostaglandin E1). Four men with poor quality MRI images were excluded from the study. The preoperative MRI was compared to final histology to assess its accuracy in predicting the invasion of the tunica albuginea and urethral invasion. Data of one hunded patients who underwent penile MRI prior to definitive surgery for invasive penil...

European Radiology

Objectives To evaluate the safety and efficacy of CT-guided IRE of clinical T1a (cT1a) renal tumo... more Objectives To evaluate the safety and efficacy of CT-guided IRE of clinical T1a (cT1a) renal tumours close to vital structures and to assess factors that may influence the technical success and early oncological durability. Methods CT-guided IRE (2015–2020) was prospectively evaluated. Patients’ demographics, technical details/success, Clavien-Dindo (CD) classification of complications (I–V) and oncological outcome were collated. Statistical analysis was performed to determine variables associated with complications. The overall 2- and 3-year cancer-specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates are presented using the Kaplan-Meier curves. Results Thirty cT1a RCCs (biopsy-proven/known VHL disease) in 26 patients (age 32–81 years) were treated with IRE. The mean tumour size was 2.5 cm and the median follow-up was 37 months. The primary technical success rate was 73.3%, where 22 RCCs were completely IRE ablated. Seven residual diseases were successf...

Journal of Vascular and Interventional Radiology

British Journal of Cancer

Background Indoleamine 2,3-dioxygenase (IDO), the first step in the kynurenine pathway (KP), is u... more Background Indoleamine 2,3-dioxygenase (IDO), the first step in the kynurenine pathway (KP), is upregulated in some cancers and represents an attractive therapeutic target given its role in tumour immune evasion. However, the recent failure of an IDO inhibitor in a late phase trial raises questions about this strategy. Methods Matched renal cell carcinoma (RCC) and normal kidney tissues were subject to proteomic profiling. Tissue immunohistochemistry and gene expression data were used to validate findings. Phenotypic effects of loss/gain of expression were examined in vitro. Results Quinolate phosphoribosyltransferase (QPRT), the final and rate-limiting enzyme in the KP, was identified as being downregulated in RCC. Loss of QPRT expression led to increased potential for anchorage-independent growth. Gene expression, mass spectrometry (clear cell and chromophobe RCC) and tissue immunohistochemistry (clear cell, papillary and chromophobe), confirmed loss or decreased expression of QPR...

BJU International

To test the hypothesis that the baseline clinico-pathological features of the men with localized ... more To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409). Patients and Methods We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models. Results The findings showed that 34% of participants (n = 505) had intermediate-or high-risk PCa, and 66% (n = 973) had lowrisk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline lowand intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins. Conclusions We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa.

Urology

OBJECTIVE To examine changes in outcome by the Leibovich score using contemporary and historic co... more OBJECTIVE To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) PATIENTS AND METHODS Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. RESULTS Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate-and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). CONCLUSION Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate-and highrisk classified patients have altered. These findings are likely to have implications for all such models used in this setting. UROLOGY 136: 162−168, 2020.

International Journal of Radiation Oncology*Biology*Physics

Organ-confined muscle-invasive bladder cancer (MIBC) is treated with cystectomy or bladder preser... more Organ-confined muscle-invasive bladder cancer (MIBC) is treated with cystectomy or bladder preservation techniques, including radiotherapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome following radiotherapy but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from two major clinical trials. Methods and Materials: Samples from the BCON and BC2001 randomised controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in three UK centres. Results: Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor inter-centre scoring agreement (Kappa 0.32, 95% CI 0.17-0.47). There were no significant associations between MRE11 scores and causespecific survival (CSS) identified in BCON (n=132) and BC2001 (n=221) samples. Reoptimised staining improved agreement between scores from BCON tissue microarrays (n=116), but MRE11 expression was not prognostic for CSS. Conclusions: Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods and/or a reassessment of how DNA-damage response relates to clinical outcomes.

British journal of cancer, Jan 11, 2018

Immunohistochemistry (IHC) is often used in personalisation of cancer treatments. Analysis of lar... more Immunohistochemistry (IHC) is often used in personalisation of cancer treatments. Analysis of large data sets to uncover predictive biomarkers by specialists can be enormously time-consuming. Here we investigated crowdsourcing as a means of reliably analysing immunostained cancer samples to discover biomarkers predictive of cancer survival. We crowdsourced the analysis of bladder cancer TMA core samples through the smartphone app 'Reverse the Odds'. Scores from members of the public were pooled and compared to a gold standard set scored by appropriate specialists. We also used crowdsourced scores to assess associations with disease-specific survival. Data were collected over 721 days, with 4,744,339 classifications performed. The average time per classification was approximately 15 s, with approximately 20,000 h total non-gaming time contributed. The correlation between crowdsourced and expert H-scores (staining intensity × proportion) varied from 0.65 to 0.92 across the mar...

Journal of Clinical Urology