Pathological upgrading and upstaging at radical prostatectomy in Jamaican men with low-risk prostate cancer.

Several studies suggest race-based health disparities in men with low-risk prostate cancer (PCa), with African American males having poorer oncological outcomes. We sought to determine the prevalence and predictors of pathological upgrading and upstaging in Jamaican men with low-risk PCa treated with radical prostatectomy (RP). Data on 141 men who met the National Comprehensive Cancer Network criteria for low-risk PCa and underwent RP at a single institution were reviewed. All men had a transrectal ultrasound-guided biopsy. Pre-operative clinical and final pathological data were obtained. Data were summarised as means and standard deviations or percentages as appropriate. Bivariate analyses such as independent samples t-tests and chi-square tables were conducted and logistic regression models were estimated to predict upgrading (>Gleason 6) and upstaging (p ≥ T3). The mean age was 59.5 ± 7.8 years with mean prostate specific antigen (PSA) of 6.6 ± 2 ng/mL. A total of 48.3% of men were upgraded and 11.4% were upstaged. Bivariate analyses indicated that PSA (p = 0.008) and percentage positive cores (p = 0.002) were associated with upgrading. PSA (p = 0.042) and percentage positive cores (p = 0.003) were significantly associated with upstaging. The odds of upgrading increased with increased PSA levels (OR 1.40, 95% CI 1.05-1.87, p = 0.021) or increased percentage positive cores (OR 8.27, 95% CI 2.19-31.16, p = 0.002). The odds of upstaging increased with increased PSA levels (OR 1.4, 95% CI 1.01-1.96, p = 0.046) and with increased percentages positive cores (OR 11.4; 95% CI 2.06-63.09, p = 0.005). Jamaican men with low-risk PCa are at high risk of pathological upgrading and upstaging at RP. These findings should be taken into consideration when discussing treatment options with these patients.

Incidental detection of germline variants of potential clinical significance by massively parallel sequencing in haematological malignancies.

Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance (TP53, RUNX1, GATA2 and WT1 in all contexts and CBL, KRAS and NRAS in the setting of juvenile myelomonocytic leukaemia) were analysed. A variant allele fraction threshold of ≥33.09% for considering germline origin of variants within cancer samples was established. The detection rate of incidental, pathogenic germline variants was 0.42%. Patient education and confirmatory germline sample testing of GVPCSs in appropriate circumstances are recommended.

PathOS: a decision support system for reporting high throughput sequencing of cancers in clinical diagnostic laboratories.

BACKGROUND: The increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout. These capabilities must be packaged in software that integrates the disparate components into a useable system. RESULTS: To meet these needs, we developed a web-based application, PathOS, which takes variant data from a patient sample through to a clinical report. PathOS has been used operationally in the Peter MacCallum Cancer Centre for two years for the analysis, curation and reporting of genetic tests for cancer patients, as well as the curation of large-scale research studies. PathOS has also been deployed in cloud environments allowing multiple institutions to use separate, secure and customisable instances of the system. Increasingly, the bottleneck of variant curation is limiting the adoption of clinical sequencing for molecular diagnostics. PathOS is focused on providing clinical variant curators and pathology laboratories with a decision support system needed for personalised medicine. While the genesis of PathOS has been within cancer molecular diagnostics, the system is applicable to NGS clinical reporting generally. CONCLUSIONS: The widespread availability of genomic sequencers has highlighted the limited availability of software to support clinical decision-making in molecular pathology. PathOS is a system that has been developed and refined in a hospital laboratory context to meet the needs of clinical diagnostics. The software is available as a set of Docker images and source code at https://github.com/PapenfussLab/PathOS .

Epididymo-orchitis causing testicular infarction: a serious complication of a common disorder.

One of the most common differentials for the acute scrotum is an epididymo-orchitis (EO), which can mimic the presentation of testicular torsion. We present a case of a 37-year-old man presented to the Emergency department with a 3-day history of progressive left testicular pain. A Doppler ultrasound was done which revealed increased flow to the left testicle with no evidence of testicular torsion and he was discharged. He was re-admitted with worsening pain and a repeat scan showed that the penile arterial diastolic flow had reversed, indicating testicular infarction. This was confirmed at exploration and an orchidectomy was performed. EO causing severe complications is an uncommon manifestation of a common disorder. Features suggesting a lack of response to antibiotics include sepsis, pronounced scrotal oedema, severe testicular pain and scrotal wall inflammation. The presence of a positive urine culture has also been highlighted as a poor prognostic factor.

Appearance of a colovesical fistula at cystoscopy.

Colovesical fistulae typically present with pneumaturia and/or fecaluria. Diverticulitis, inflammatory bowel disease, and malignancies of the colon are the commonest causes. The fistulous tract and adjacent organs are best demonstrated by contrast-enhanced CT scan with rectal contrast or MRI. Biopsy at cystoscopy/colonoscopy is necessary for complete evaluation and treatment planning.

A delayed foreskin-sparing approach to the management of penile fractures in uncircumcised Jamaican men.

INTRODUCTION: The traditional surgical approach to penile fracture is to perform a circumferential subcoronal degloving incision emergently to repair the injury. This approach necessitates circumcision to avoid foreskin complications. We present four men who had a delayed foreskin-sparing approach and discuss its advantages. PRESENTATION OF CASE: Four of five uncircumcised patients who had suspected penile fractures secondary to coital injury, and without suspicion of concomitant urethral injury, had a delayed exploration, seven days after injury, utilizing an incision directly over the palpable haematoma, at the location of the tunical defect, thereby resulting in foreskin preservation. Two of 5 patients had repair under general anaesthesia, one under local anaesthesia and surgery was cancelled in another because upon reassessment at seven days he had normal erections and a normal penile examination. At follow up, all men had good functional and cosmetic outcomes. DISCUSSION: Uncircumcised patients with penile fractures, without suspicion of urethral injury, may undergo a delayed repair without prophylactic circumcision since there is minimal risk of foreskin complications. Delayed repair decreases the incidence of negative explorations by fostering a conservative approach in mimicking conditions such as superficial vein lacerations. It also enables the use of local anaesthesia in an elective ambulatory setting. CONCLUSION: Delayed repair of penile fractures results in foreskin preservation, facilitates elective ambulatory care under local anaesthesia and decreases the incidence of negative surgical explorations.