Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis.

OBJECTIVE: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). METHODS: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. RESULTS: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. CONCLUSION: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN.

Adjuvant immune checkpoint inhibitors for urothelial carcinoma: systematic review and Meta-analysis.

PURPOSE: To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery. METHODS: This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling. RESULTS: Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively. CONCLUSION: Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Prostate cancer mortality rates in low- and favorable intermediate-risk active surveillance patients: a population-based competing risks analysis.

PURPOSE: To determine prostate cancer (PCa) and other-cause mortality rates in low- and favorable intermediate-risk (FIR) active surveillance (AS) patients. METHODS: The SEER Prostate with Watchful Waiting database was used to identify men diagnosed with NCCN low or FIR PCa, between 2010 and 2015, managed with AS. FIR patients were subdivided into three subgroups, based on their intermediate risk factor: grade group two (GG2), PSA 10-20 ng/ml or cT2b-c disease. Cumulative incidence function curves with other-cause mortality as the competing risk were utilized. Predictors of PCa mortality were assessed using multivariable regression analysis with semi-parametric proportional hazards modeling. RESULTS: Among 70,871 patients, 48,127 (67.9%) had low and 22,744 (32.1%) had FIR disease. Median patient age was 64.0 years, and median PSA was 5.70 ng/ml. Median follow-up was 49.0 months. There were 166 (0.2%) PCa and 3,176 (4.48%) other-cause mortalities. The 5-year mortality rates in the low and FIR cohorts overall were 0.29% and 0.28%, respectively (p = 0.64). Within the FIR cohort, the corresponding rates were highest in the PSA 10-20 ng/ml subgroup at 0.73%, followed by 0.32% for GG2 FIR and 0.052% for cT2b-c FIR disease (p < 0.001). Older age at diagnosis (sHR 2.38, p = 0.006), Medicaid insurance (sHR: 2.58, p < 0.001), low socioeconomic (sHR 1.39, p = 0.032), and non-married statuses (sHR: 2.58, p < 0.001) were associated with increased PCa mortality. CONCLUSION: Intermediate-term PCa mortality rates in FIR PCa patients are non-significantly different to those with low-risk PCa. However, there is significant within-group heterogeneity, with PCa mortality rates significantly higher in the PSA 10-20 subgroup.

Suspension of Oncology Randomized Clinical Trials during the COVID-19 Pandemic: A Cross-Sectional Evaluation of COVID-Related Suspensions.

We conducted a cross-sectional analysis of ClinicalTrials.gov-registered oncology randomized controlled trials between September 2019 and December 2021 to identify predictors of trial suspensions. The dataset included 1,183 oncology trials, of which 384 (32.5%) were suspended. COVID-19 accounted for 47 (12.2%) suspensions. Trials that were single center- or US-based had higher odds of COVID-19 (ORs: 3.85 and 2.48, 95% CIs: 1.60-11.50 and 1.28-4.93, respectively) or any-reason suspensions (ORs: 2.33 and 2.04, 95% CIs: 1.46-3.45 and 1.40-2.76, respectively). Phase two (OR 1.27), three (OR 6.45) and four trials (OR 11.5) had increased odds of COVID-19 suspensions, compared to phase one trials.

Transparency of racial participation reporting in randomized controlled trials of minimally invasive surgical techniques.

BACKGROUND: Enrolment of racial/ethnic minorities in randomized controlled trials (RCTs) has historically been poor, despite efforts at improving access to RCTs. Under-representation of racial/ethnic minorities limits the external validity and generalizability of trials. Our objective was to determine to what extent are published RCTs of minimally invasive surgical techniques reporting the racial composition of their study cohorts and to describe the racial composition of patients enrolled in these trials, where data were available. METHODS: EMBASE (OvidSP®), MEDLINE (OvidSP®), and Cochrane (Wiley®) databases were systematically searched from inception to December 22, 2017 to identify all RCTs comparing minimally invasive and classical surgical techniques. The Mann-Kendall trend test was used to evaluate reporting trends over the study period. Predictors of racial reporting were evaluated using logistic regression analyses. RESULTS: Our search strategy yielded 9,321 references of which 496 RCTs met our inclusion/exclusion criteria. Racial information was reported in 20 (4.03%) studies. There was no significant improvement in racial reporting over the study period (p for trend = 0.31). Of the 17 different patient populations accounting for the 20 RCTs, 14 (82.4%) originated from the USA. Multicenter RCTs had significantly increased likelihood of reporting racial composition of the patient cohort (odds ratio 5.10, p = 0.025). White/Caucasian patients accounted for 84.5% of the pooled patient population, with Black/African American, Asian and Latin/Hispanic patients accounting for 7.9%, 1.2%, and 2.1%, respectively. CONCLUSIONS: Among RCTs assessing minimally invasive surgical techniques over the past 30 years, data on included patients' race is poorly reported. In addition to important efforts to improve access to clinical trials for racial and ethnic minorities, efforts aimed at improving reporting and transparency of surgical RCTs are sorely needed.

Formulation of Suppositories of Alum Produced from Bauxite Waste in Ghana for the Treatment of Hemorrhoid.

The study sought to formulate and evaluate suppositories using a locally produced brand of alum (Aw) obtained from bauxite waste generated at Awaso bauxite mine in the Western-North region of Ghana, for use in the treatment of hemorrhoids. The suppositories were formulated using shea butter modified, respectively, with amounts of beeswax and theobroma oil. In another development, theobroma oil was modified with different concentrations of beeswax. Drug-base interactions were investigated using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The suppositories were prepared using the hot melt and trituration methods. Quality control checks were carried out on the formulations. The evaluated parameters included physical characteristics (texture, presence or absence of entrapped air, and contraction holes), weight uniformity, disintegration time, drug content, and in vitro release profile of the alum from the formulated suppositories. An in vivo analysis was carried out on the most suitable formulation to ascertain its efficacy on inflamed tissues using croton oil-induced rectal inflammation in a rat model. A critical examination of the ATR-FTIR spectra revealed no drug-base interactions. The suppository formulations passed all Pharmacopoeia stated tests. The in vivo study revealed the use of suppositories ameliorated the croton oil-induced hemorrhoid in the rectoanal region of the rats.

Cancer diagnosis and risk of suicide after accounting for prediagnosis psychiatric care: A matched-cohort study of patients with incident solid-organ malignancies.

BACKGROUND: Previous studies have demonstrated an association between a diagnosis of cancer and the risk of suicide; however, they failed to account for psychiatric care before a cancer diagnosis, which may confound this relationship. The objective of this study was to assess the effect of a cancer diagnosis on the risk of suicide, accounting for prediagnosis psychiatric care utilization. METHODS: All adult residents of Ontario, Canada who were diagnosed with cancer (1 of prostate, breast, colorectal, melanoma, lung, bladder, endometrial, thyroid, kidney, or oral cancer) between 1997 and 2014 were identified. Noncancer controls were matched 4:1 based on sociodemographics, including a psychiatric utilization gradient (PUG) score (with 0 indicating none; 1, outpatient; 2, emergency department; and 3, hospital admission). A marginal, cause-specific hazard model was used to assess the effect of cancer on the risk of suicidal death. RESULTS: Among 676,470 patients with cancer and 2,152,682 matched noncancer controls, there were 8.2 and 11.4 suicides per 1000 person-years of follow-up, respectively. Patients with cancer had an overall higher risk of suicidal death compared with matched patients without cancer (hazard ratio, 1.34; 95% CI, 1.22-1.48). This effect was pronounced in the first 50 months after cancer diagnosis (hazard ratio, 1.60; 95% CI, 1.42-1.81); patients with cancer did not demonstrate an increased risk thereafter. Among individuals with a PUG score 0 or 1, those with cancer were significantly more likely to die of suicide compared with controls. There was no difference in suicide risk between patients with cancer and controls for those who had a PUG score of 2 or 3. CONCLUSIONS: A cancer diagnosis is associated with increased risk of death from suicide compared with the general population even after accounting for precancer diagnosis psychiatric care utilization. The specific factors underlying the observed associations remain to be elucidated.

The impact of psychiatric utilisation prior to cancer diagnosis on survival of solid organ malignancies.

BACKGROUND: Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS: All residents of Ontario diagnosed with one of the top 10 malignancies (1997-2014) were included. The primary exposure was psychiatric utilisation gradient (PUG) score in 5 years prior to cancer: 0: none, 1: outpatient, 2: emergency department, 3: hospital admission. A multivariable, cause-specific hazard model was used to assess the effect of PUG score on cancer-specific mortality (CSM), and a Cox proportional hazard model for effect on all-cause mortality (ACM). RESULTS: A toal of 676,125 patients were included: 359,465 (53.2%) with PUG 0, 304,559 (45.0%) PUG 1, 7901 (1.2%) PUG 2, and 4200 (0.6%) PUG 3. Increasing PUG score was independently associated with worse CSM, with an effect gradient across the intensity of pre-diagnosis PU (vs PUG 0): PUG 1 h 1.05 (95% CI 1.04-1.06), PUG 2 h 1.36 (95% CI 1.30-1.42), and PUG 3 h 1.73 (95% CI 1.63-1.84). Increasing PUG score was also associated with worse ACM. CONCLUSIONS: Pre-cancer diagnosis PU is independently associated with worse CSM and ACM following diagnosis among patients with solid organ malignancies.

Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current Guidelines.

PURPOSE: Radical cystectomy is inherently associated with morbidity. We assess the timing and incidence of venous thromboembolism, review current guideline recommendations and provide evidence for considering extended venous thromboembolism prophylaxis in all patients undergoing radical cystectomy. MATERIALS AND METHODS: We searched PubMed® for available literature on radical cystectomy and venous thromboembolism, focusing on incidence and timing, evidence supporting extended venous thromboembolism prophylaxis in patients undergoing radical cystectomy or abdominal oncologic surgery, current guideline recommendations, safety considerations and direct oral anticoagulants. Search terms included "radical cystectomy," "venous thromboembolism," "prophylaxis," and "extended oral anticoagulants" and "direct oral anticoagulants" alone and in combination. Relevant articles were reviewed, including original research, reviews and clinical guidelines. References from review articles and guidelines were also assessed to develop a narrative review. RESULTS: The incidence of symptomatic venous thromboembolism in short-term followup after radical cystectomy is 3% to 11.6%, of which more than 50% of cases will occur after hospital discharge. Meta-analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis. Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively. Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration. CONCLUSIONS: Patients undergoing radical cystectomy are at high risk for venous thromboembolism after hospital discharge. There is strong evidence that extended prophylaxis significantly decreases the risk of venous thromboembolism in oncologic surgery cases. Use of extended prophylaxis after radical cystectomy has been poorly adopted, emphasizing the need for better adherence to current urology procedure specific guidelines as extended prophylaxis for radical cystectomy is the standard of care. Specific and rare circumstances may require case by case assessment.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PURPOSE: We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. MATERIALS AND METHODS: We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. RESULTS: Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. CONCLUSIONS: Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

First Report of Phomopsis Stem Canker of Sunflower (Helianthus annuus) Caused by Diaporthe gulyae in Canada.

During September 2012, Phomopsis stem canker was observed on sunflowers (Helianthus annuus L.) in a production field during seed filling with an average incidence of 15% in Morden, Manitoba (approximately 49°11'N and 98°09'W). The infected plants had elongated, brown-black lesions surrounding the leaf petiole, with numerous pycnidia, pith damage, and mid-stem lodging. Twenty sunflower plants were randomly sampled from the field. Isolations were made from the margins of the necrotic stems lesions by plating small pieces (5 mm) on potato dextrose agar (PDA) amended with 0.02% streptomycin sulfate. Plates were incubated at 25°C for 14 days under a 12-h photoperiod, and hyphal tips of white to grey colonies were transferred to PDA. Five isolates producing black pycnidia (occasionally with ostiolate beaks) and alpha conidia were tentatively identified as a Diaporthe sp. Alpha conidia were ellipsoidal, hyaline, and 6.5 to 8.5 × 2.5 to 3.5 µm. DNA was extracted from the mycelium of five isolates, and the ITS region was amplified and sequenced using primers ITS5 and ITS4 (4). BLASTn analysis of the 600-bp fragment (GenBank Accession Nos. KM391960 to KM391964) showed that the best match was Phomopsis sp. AJY-2011a strain T12505G (Diaporthe gulyae R.G. Shivas, S.M. Thompson & A.J. Young [3], Accession No. JF431299) from H. annuus with identities = 540/540 (100%) and gaps = 0/540 (0%). The five D. gulyae isolates were tested for pathogenicity on a sunflower confection inbred cv. HA 288 using the stem-wound method (2). Four-week-old sunflower plants (10 plants per isolate) were inoculated by wounding the stems on the second internode with a micropipette tip and placing a Diaporthe-infested mycelial plug on the wound. All plugs were attached to the wound with Parafilm. The pots were placed on the greenhouse benches at 25°C under a 16-h light/dark cycle. At 3 days after inoculation, dark brown lesions were observed on the stems extending upward from the inoculation site. Stem and leaves wilted, causing plant death 14 days after inoculation. Disease severity was calculated as a percentage of stem lesion (lesion length/stem length × 100%) at 14 days after inoculation. Significant differences (P ≤ 0.05) in disease severity were observed among D. gulyae isolates, which ranged from 34.9 to 100.0% (n = 5). Ten control plants similarly treated with sterile PDA plugs did not display symptoms. To complete Koch's postulates, D. gulyae was re-isolated from the inoculated stems, and the pathogen's identity was confirmed via sequencing of the ITS regions using primers ITS5 and ITS4 (4). The pathogen was not isolated from the control plants. D. gulyae was first reported as a pathogen on H. annuus in Australia and United States in 2011 (1,3). The pathogen was determined to be as or more aggressive than the other causal agents of Phomopsis stem canker (2,3), and its identification in both countries was circumstantially associated with increased incidence and yield loss in commercial production fields (1,3). In Canada, Phomopsis stem canker has been observed in sunflower fields over the last 10 years at low incidences, especially in years with above-normal temperatures during the sunflower growing season; however, the causal agent was not confirmed. To the best of our knowledge, this is the first report of D. gulyae causing Phomopsis stem canker on sunflowers in Canada. Since there is currently no known resistance to D. gulyae in sunflower, this newly discovered pathogen may become a threat to sunflower production in Canada. References: (1) F. Mathew et al. Phytopathology 101:S115, 2011. (2) F. Mathew et al. Phytopathology 103:S2.91, 2013. (3) S. M. Thompson et al. Persoonia 27:80, 2011. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

Wound Infection in Surgical Ward of a Tertiary Care Hospital in Dhaka City: The Identification of Organisms and Their Sensitivity Pattern.

Wound infection is one of the most important causes of morbidity and mortality worldwide. The aim of this study was to identify the organisms and their sensitivity pattern from wound infection patients attending in a tertiary care hospital in Dhaka city. This cross-sectional study was carried out in a total of 240 aseptically collected wound swab samples from wound infection suspected patients visiting Bangladesh Medical College Hospital, Dhaka, Bangladesh were analyzed from July 2017 to June 2019. Bacteriological culture of the samples, colony morphology, Gram's staining, and biochemical tests were done following standard microbiological techniques. The antimicrobial susceptibility testing was performed by modified Kirby-Bauer disc diffusion technique following clinical and laboratory standards institute guidelines. Out of 240 wound swab samples from suspected patients of wound infection, 126(52.5%) showed bacterial growth whereas 114(47.5%) were culture negative. No sample yielded more than one organism. Among 126 culture positive cases 75(59.52%) were male and 51(40.48%) were female. The higher rate of bacterial infections 26.19% was noted in the age group of 21-30 years, followed by the age group of 31-40 years, 41-50 years, 51-60 years. Among 126 culture positive cases, 74.6% were Gram negative and 25.4% were Gram positive bacteria. Out of total 126 isolates, E. coli was the most prevalent pathogen 31(24.60%) followed by Staphylococcus aureus 29(23.01%); Pseudomonas 27(21.43%); Klebsiella 18(14.29%); Enterobacter 12(9.52%); Acinetobacter 4(3.17%), while Coagulase negative Staphylococcus 3(2.38%) and Proteus 2(1.59%) were least detected isolates in wound swab. Highly effective antibiotics against Staph aureus were vancomycin 100.0%; imipenem 100.0%; linezolid 100.0% and meropenem 89.65%. Amikacin; gentamicin; netilmicin; imipenem and meropenem showed higher sensitivity in E coli, Klebsiella and Enterobacter species. Colistin was 88.88% effective against Pseudominas spp. followed by imipenem 81.48%, piperacillin-tazobactam 77.78%, meropenem 70.37% and amikacin 51.85%. Acinetobacter spp. showed 75.0% and 50.0% sensitivity to netilmicin and colistin respectively. Injectable and reserve drugs were sensitive to bacterial populations among patients of wound infections in our hospital. It is a wake-up call for clinician to treat wound infections. To prevent the increase resistance to antibiotics, it is necessary to avoid the administration of uncontrolled and unnecessary antibiotics available.

Association of extended core sampling with delayed intervention and pathologic outcomes for active surveillance patients A population-based analysis.

INTRODUCTION: Combined systematic plus targeted biopsy sampling improves detection of clinically significant prostate cancer (PCa). Our objective was to evaluate whether extended core sampling at initial biopsy in active surveillance (AS) patients is associated with subsequent AS discontinuation and pathologic outcomes. METHODS: National Comprehensive Cancer Network (NCCN) low- and favorable-intermediate-risk (FIR) AS patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database. Prostate biopsy sampling was operationalized as: standard (10-12 cores), extended (13-20 cores), or super-extended (21+ cores). Sensitivity analyses using differing cutoffs was performed. Outcomes included delayed definitive intervention (radical prostatectomy [RP]/radiotherapy) and pathologic upgrading and/or downgrading in delayed RP patients. Multivariable logistic regression modelling adjusted for sociodemographic/oncologic variables was performed. RESULTS: This cohort included 42 459 patients (low-risk: 28 411; FIR:14 048); 25-29% and 3-5% of patients underwent extended and super-extended core sampling, respectively, at diagnosis. Extended core sampling was associated with decreased odds of definitive intervention in low (odds ratio [OR] 0.89, p=0.003) and grade group 2 (GG2) FIR (OR 0.83, p=0.002) patients. Super-extended sampling was associated with decreased odds of definitive intervention in prostate-specific antigen (PSA) 10-20 FIR patients (OR 0.65, p=0.02). Super-extended sampling was associated with decreased odds of upgrading to ≥GG2 disease in low-risk (OR 0.45, p=0.032) and to ≥GG3 disease in GG2 FIR patients (OR 0.67, p=0.044). CONCLUSIONS: This population-based analysis demonstrates that extended/super-extended sampling at diagnosis is associated with significantly decreased odds of AS discontinuation and pathologic upgrading in low/FIR AS patients. This highlights the significance of extended tissue sampling at initial biopsy to appropriately risk-stratify AS patients and minimize AS discontinuation rates.

Using active surveillance for Gleason 7 (3+4) prostate cancer: A narrative review.

The interest in broadening the application of active surveillance (AS) has been increasing, encompassing patients who may not strictly adhere to the conventional criteria for low-risk prostate cancer (PCa), particularly those diagnosed with small-volume Gleason grade group 2 disease. Nonetheless, accurately identifying individuals with low intermediate-risk PCa who can safely undergo AS without facing disease progression remains a challenge.This review aims to delve into the progression of this evolving trend specifically within this cohort of men, while also examining strategies aimed at minimizing irreversible disease advancement. Additionally, we address the criteria for patient selection, recommended followup schedules, and the indicators prompting intervention.