Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.

Introduction: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. Methods: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. Results: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). Conclusion: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette-Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.

Jackstone in the Kidney: An Unusual Calculus.

Jackstones are stones in the urinary tract that have the characteristic appearance resembling six-pointed toy jacks. They are nearly always reported to occur in the urinary bladder, and the occurrence in less capacious renal pelvis is unusual. We report a solitary, typical jackstone in the renal pelvis without significant outflow obstruction that was successfully treated with retrograde intrarenal surgery followed by extracorporeal shockwave lithotripsy. This highlights the complex pathophysiological mechanisms in stone formation which needs to be further studied. It is important to recognize the characteristic shape of the renal calculi on the radiological investigation in the diagnosis of the jackstones.

Clinicopathological patterns and outcomes of urothelial bladder malignancies in Sri Lankan patients.

INTRODUCTION: Studies on bladder cancer in Sri Lanka have shown varying results in relation to clinicopathological characteristics and data on outcomes is limited. This study was aimed to describe the clinicopathological characteristics and outcomes of histologically confirmed urothelial bladder malignancies and to compare with previous studies. METHODS: A retrospective analysis of prospectively collected data of 314 newly diagnosed primary bladder malignancies between January-2007 and January-2017, was performed. After excluding the non-urothelial cancers, 289(92%) urothelial cancers (males=245, 84.8%, mean age = 65.4±SD10.9 years) were analysed. Data on clinical presentation, cystoscopic findings, histopathology and outcomes were studied. RESULTS: The majority (87.9%, n=254) presented with haematuria with a median duration of symptoms of 1 month. Non-muscle invasive cancers were seen among 64.4% (pTa:n=87(30.1%),pT1:n=99(34.3%)). The pT1 high grade (pT1-HG) tumours were seen in 17.5%. Muscle invasive bladder cancer (MIBC) were seen in 35.6%(n=103). The majority were high grade tumours (n=156,54%). Urothelial MIBC were significantly associated with solid tumours (p<0.001), high grade (p<0.001) and size>3cm (p<0.001). Comparison with previous studies showed a decline in the proportion of MIBC while the pT1-HG tumours are on the rise. Of those followed up, 52.5% developed recurrences with a median duration of 4 months (interquartile range (IQR): 3-12 months). Eighteen (9%) progressed to a higher stage with a median duration of 17 months (IQR:3.75-41.75). CONCLUSIONS: Urothelial cancer in the study population was 92%. Higher proportion of MIBC, high grade tumours and pT1-HG tumours were noted. The recurrence rate was high. Future studies should focus on the causative factors for this trend.

Bladder cancer in women: a Sri Lankan study

Introduction: Bladder cancer (BC) is the ninth commonest cancer globally, and ranks 19th among women. The literature on BC in women is sparse, and the knowledge on the variations of tumour characteristics in South Asian female BC is limited. The objective of this study was to describe the clinicopathological characteristics of BC in women and compare them with male BC. Methods: A retrospective analysis of all female patients with histopathologically proven newly diagnosed primary BC from January 2007 to January 2017 was done at the Urology Unit, National Hospital of Sri Lanka, and the findings were compared with men with BC during the same period. Results: There were 314 patients with primary BC, of which 55(17.5%) were women, with a male:female ratio of 4.7:1. Only 70.9% of women had haematuria at presentation. Forty-four women (80%) had urothelial bladder cancers(UBC). The mean age of women with UBC was 67±SD13.2 years, and for non-urothelial bladder cancers(NUBC) was 62.5±SD 12.7 years. NUBC in women accounted for a disproportionately higher percentage in comparison to men (20% vs.5.4%, p<0.001). Of the UBCs, muscle invasive BC accounted for 45.5% (20/44) in women as opposed to 33.5% (82/245) in men. Women had a significantly higher proportion of solid tumours (40%vs.22.8%,p=0.008) compared to men. Conclusion: Primary BC in women has a significantly higher proportion of NUBC and muscle invasive UBC, which are more aggressive cancers, compared to men. Furthermore, the lack of haematuria in >25%, and higher incidental diagnosis, with inherently thinner bladder wall, makes primary BC in women more likely to present late, in a more advanced state.

Testicular adrenal rest tumour in an adult patient with congenital adrenal hyperplasia: a case report and review of literature.

Late presentations of testicular adrenal rest tumours (TART) are rarely seen in males with congenital adrenal hyperplasia, and are often misdiagnosed as primary testicular germ cell tumours. We report a case of bilateral TART in an adult patient with congenital adrenal hyperplasia who had defaulted treatment. He presented with a gradually increasing swelling of the left testis and genital examination revealed a large hard indurated swelling of both epididymes more prominent on the left side. As imaging was inconclusive, a biopsy was performed which showed features in favour of TART rather than Leydig cell neoplasm and he had good response to steroids. Histopathological evaluation is helpful in cases where there is a strong need for excluding a malignancy. Optimal steroid replacement is the treatment of choice and leads to regression of the lesion in the majority.

Retrocaval ureter associated with cryptorchidism: A case report and review of literature.

We report an incidentally diagnosed retrocaval ureter in a 14-year-old boy, while evaluating for right-sided hydronephrosis associated with cryptorchidism. Therefore, we suggest that any significant right-sided hydronephrosis associated with cryptorchidism may require investigations to exclude this rare anomaly.

Complete necrosis of graft ureter following renal transplant in a patient with primary antiphospholipid syndrome: A case report.

Complete necrosis of the graft ureter is a rare but serious complication following kidney transplant. In a patient with antiphospholipid syndrome, a combination of factors such as arterial thromboembolism, hematoma formation, and surgical collateral damage can cause ischemia of the graft ureter. Preoperative optimization of disease activity and coagulation with meticulous preservation of ureteric perfusion may help in prevention.

Partial cystectomy for a primary locally advanced leiomyosarcoma of the bladder: a case report and review of the literature.

Partial cystectomy with wide local excision may be considered a suitable option for selective cases of locally advanced bladder leiomyosarcoma without evidence of distant metastasis; thereby preserving the functional outcome and quality of life. A negative margin, complete tumor resection, and frequent follow-up in such patients are mandatory.

Aggressive squamous cell carcinoma of the bladder associated with a history of large bladder stone - a case report.

History of large bladder stones suggests a long-standing chronic irritation of the bladder, a known risk factor for squamous cell carcinoma. Therefore, in such patients, we suggest random biopsies to detect presence of dysplasia or malignancy and a follow-up cystoscopy for early detection of a possible tumor.

Jack stone in the bladder: case report of a rare entity.

BACKGROUND: Jackstone is a bladder stone that has a similar appearance to toy jacks. However review of the English language medical literature revealed only a few previous reports of jackstone calculus. CASE PRESENTATION: We report a case in which a large jackstone calculus was incidentally detected during the evaluation of 67 year old male presenting with lower urinary tract symptoms. X-Ray kidney, ureter, bladder showed a large irregular shaped radio-opaque shadow in the pelvic region. He underwent cystolitholapaxy and transurethral resection of the prostate. CONCLUSION: It is important to recognize the characteristic shape of the urinary bladder calculi in the diagnosis of the jack stones and to treat the primary cause of calculi formation.