The Role of Suprapubic Superficial Fascial System Reconstruction During Repair of Adult-Acquired Buried Penis.

BACKGROUND: Adult-Acquired Buried Penis is a disorder associated with systemic obesity that confers increased risks of malignancy, sexual dysfunction, urinary abnormalities, and psychological distress. Surgical correction improves patient-reported functional and psychological outcomes and often requires collaboration between plastic and urologic surgeons. To improve postoperative cosmetic outcomes and decrease wound complications following adult-acquired buried penis repair, we performed an anatomic and histologic study of the superficial fascial layers providing support to the external male genitalia and describe our approach for fascial reconstruction. METHODS: We characterized the superficial fascial anatomy in three patients undergoing adult-acquired buried penis repair, including two patients with Wisconsin Type II disease and one patient with Wisconsin Type IV disease. Gross specimens were sent from two patients histologic analysis using H&E and elastin-specific stains to characterize the identity of the superficial fibrofatty tissue. RESULTS: In all three patients, the fundiform ligament overlying the suspensory ligament was identified, isolated, and transected for removal with the suprapubic specimen. We found that reapproximation of this ligament following transection at the time of escutcheonectomy provided significant lift to the penis and genitals via improved support of dartos fascia. Histologic analysis of the superficial fibrofatty tissue located beneath the dermis revealed histologic similarities with the superficial fascial system described previously in abdominal and breast tissue. CONCLUSIONS: Reapproximation of the fundiform ligament and superficial fascial tissue following suprapubic/lower abdominal fat pad removal during adult-acquired buried penis may improve postoperative cosmesis by reducing strain on the dermal closure. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma.

SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied clinicopathologic features of 7 cases of locally advanced ccRCC with single SETD2 mutation, and compared to 7 cases of locally advanced ccRCC with single BAP1 mutation. SETD2-mutated ccRCC showed high-grade transformation, comprising of enlarged tumor cells with voluminous clear cytoplasm, enlarged irregular nuclei with prominent nucleoli, eosinophilic cytoplasmic granules, arranged in various architectural patterns such as large nested, tubular, tubulopapillary and solid. 71 % (5 of 7 cases) of SETD2-mutated ccRCC showed a rhabdoid morphology. SETD2-mutated ccRCC have striking propensity for invasive growth; all cases have vascular invasion and perirenal (extracapsular) adipose tissue invasion. After nephrectomy, distant metastasis was found in 67 % (4 of 7 cases) of patients with SETD2-mutated ccRCC. The most common metastatic site was the lung (3 cases), followed by precaval lymph nodes (1 case). BAP1-mutated ccRCC also showed a similar high-grade morphology, with rhabdoid and/or sarcomatoid features. Their high-grade features mostly overlapped with those of SETD2-mutated ccRCC, which makes difficult to predict the presence of BAP1 or SETD2 mutation solely from morphology. These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.

Utility of cytopathologic diagnosis of adult solid renal lesions: An academic Institution's 10-year experience.

BACKGROUND: Fine needle aspiration (FNA) and/or needle core biopsy (NCB) are increasingly used for managing patients with renal lesions, especially small renal masses (SRMs). One of the treatment options for SMRs is active surveillance. Hence, accurate diagnosis of renal lesions is critical for treatment planning. The aim of this study is to investigate the utility of FNA and/or NCB in the diagnosis of adult renal lesions at our institute. MATERIALS AND METHODS: Laboratory information system was queried over a period of 10 years (2011-2020) to identify cases of FNA and/or NCB with touch preparation (TP) of adult renal masses. Patient demographics, cytopathologic diagnoses, ancillary tests and follow-up surgical resection data were reviewed and correlated. RESULTS: A total 138 cases from 138 patients (male = 80, female = 58) were identified. Sixty-one (44.20%) cases had FNA and NCB, 48 (34.78%) had NCB only and 29 (21.01%) had FNA only. 118 (85.50%) cases had definitive diagnoses and 13 (9.42%) had indeterminant diagnoses and seven cases were non-diagnostic (5.07%). Most common benign and malignant diagnoses were oncocytoma and clear cell renal cell carcinoma (CCRCC). 41/138 (29.71%) cases had follow-up resection. There were no false positive or false negative cases. Subtyping was feasible in majority cases with only 3/138 (2.17%) misclassified cases. CONCLUSIONS: Majority of renal masses (85.50%) had definitive cytology diagnoses. Only three had misclassification. FNA and/or NCB are useful methods in diagnosing and subclassifying adult renal masses and showed high accuracy (91.89%) when compared to surgical resections.

Acute psilocybin enhances cognitive flexibility in rats.

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.

Molecular Characterization of Malignant Renal Epithelioid Angiomyolipoma: A Review of Two Cases.

OBJECTIVES: Epithelioid angiomyolipoma (EAML, perivascular epithelioid cell tumor) is an uncommon primary renal tumor that may recur or metastasize, although there remain limited data for prediction of these outcomes. Here, we report two cases of renal EAML with molecular testing, adding to the existing literature of potential alterations associated with malignant behavior. METHODS: Tumors diagnosed as malignant renal EAML were identified, and clinical data, radiology, histology, immunohistochemistry, and molecular testing results were reviewed. RESULTS: Two cases of malignant renal EAML were identified, both of which demonstrated TSC2 and TP53 mutations. In ATRX, one had a mutation and the other had a variant of uncertain significance. In addition, one patient had a synchronous classic angiomyolipoma that lacked TP53 and ATRX alterations. CONCLUSIONS: These findings highlight the molecular landscape of malignant renal EAML and expand on the existing literature suggesting a role for TP53 and ATRX alterations in malignant progression of these tumors. The presence of synchronous benign and malignant tumors within the same patient offers a unique opportunity to directly compare the molecular alterations, further supporting the association with aggressive behavior.

Acute psilocybin enhances cognitive flexibility in rats.

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.

Pure post-pubertal yolk sac tumor of the testis: An extremely rare and aggressive entity.

CONTEXT: Pure post-pubertal yolk sac tumors (YSTs) are an extremely rare type of malignant germ cell tumor (GCT) that account for <1 % of testicular GCTs. Clinically, they are more aggressive compared to the more common pre-pubertal counterpart. The aim of this study is to analyze the clinical presentation, ancillary tests and clinical outcomes in addition to presenting a spectrum of histomorphological features, in a case series along with a literature review. DESIGN: A retrospective review of 4 cases of pure post-pubertal YST of the testis was performed. Data collected for each patient included demographics, clinical presentation, serum markers, radiology and pathologic findings, treatment, and clinical outcomes. RESULTS: All patients presented with a testicular mass with or without associated pain and elevated serum alpha-feto protein. Mean age at presentation was 36 years (range 25-68 years). Two patients presented with metastatic disease at the time of diagnosis. Histologic patterns and features are as follows: germ cell neoplasia in-situ (n = 4), reticular/microcystic, solid, glandular, papillary, endometrioid, cystic, necrosis and angiolymphatic invasion (n = 3). Fluorescent in-situ hybridization test performed on Case 2, showed presence of isochromosome 12p and next generation sequencing showed gains of 12p. Case 1, 2 and 4 showed metastatic disease on follow-up. CONCLUSIONS: Diagnosis of pure post-pubertal YST remains challenging due to the variety of morphologic patterns often present in these tumors. Extensive sampling along with use of ancillary tests is the key for diagnosis. In this study, 75 % of cases had metastatic disease at or after the diagnosis confirming the aggressive nature of this rare entity.

Extramammary paget disease of the penoscrotal region.

Extramammary Paget disease is an uncommon slow growing intraepithelial malignant neoplasm. It can be classified into primary and secondary subtypes, with secondary subtype associated with underlying malignancy. Extramammary Paget disease of the penoscrotal region is extremely rare with very limited literature available describing its clinicopathologic characteristics. We present 6 cases of penoscrotal EMPD diagnosed at our academic medical center over a 20 year period. These included 5 cases of scrotal EMPD and 1 case of penile EMPD. The mean age at diagnosis was 68.6 yrs. (Range 61-78 years), One case of scrotal EMPD had history of renal cell carcinoma and prostatic adenocarcinoma, while one other case presented as recurrent EMPD with initial disease in the left groin. EMPD in the glans penis was associated with a history of urothelial carcinoma in the ureter with pagetoid spread. 3 cases had no progression of the disease till recent follow up, 2 were lost to follow up while 1 case rapidly deteriorated resulting in death. This case had bone metastatic and associated peritoneal carcinomatosis. Thus, Extramammary Paget disease of the penoscrotal area is extremely rare, can be primary or associated with visceral malignancies and usually tends to present at an older age. Peritoneal spread and distant metastasis are associated with rapid progression of the disease.

Malignant germ cell tumors in men aged 50 years and over are associated with adverse pathologic features and higher stage at presentation.

BACKGROUND: Germ cell tumors (GCT) are the most common malignancy in men in the third and fourth decades of life. The occurrence of malignant GCT in men aged 50 years or over is rare, and their histopathologic characteristics and outcome is insufficiently characterized in the medical literature. Hence, we report the histopathologic features and clinical outcome of malignant GCTs in men aged ≥50 years at our institution. DESIGN: We performed a retrospective search of our database from 2005 to 2021 to identify men aged 50 years or older with malignant GCT. Cases of spermatocytic tumor were excluded. Clinical and histopathologic features of the tumors were reviewed. RESULTS: Forty-seven cases were identified, showing a sharp decline in incidence over the age of 65. Thirty-nine (83 %) tumors were testicular while eight (17 %) were non-testicular in presentation. Cases included 26 (55 %) seminomas, 15 (32 %) non-seminoma/mixed malignant GCT, and 5 (11 %) regressed testicular germ cell tumors. The most common component in mixed malignant GCTs was embryonal carcinoma (77 %), followed by seminoma and yolk sac tumor (62 % each). Germ cell neoplasia in situ (GCNIS) accompanied 57 % of the cases. Aggressive pathologic features, including lymphovascular invasion, retroperitoneal/lymph node involvement and higher stage at presentation, were identified in a significant proportion of cases (36/47, 77 %). Clinical follow up showed six patients (14 %) died of disease-related causes. CONCLUSION: Our findings expand and corroborate the previously reported data on malignant GCT in older men. Unique characteristics include tendency for higher stage at presentation with adverse pathologic features and more aggressive clinical course.

The osteoclast-type giant cell rich carcinoma of urinary bladder: A case series.

BACKGROUND: Osteoclast-type giant cell-rich carcinomas (OGCRCs) of urinary bladder are extremely rare, aggressive tumors that are often diagnosed as undifferentiated carcinomas. The morphology overlaps with other giant cell-rich benign and malignant bladder lesions. Little is known about the pathogenesis and clinical management of this aggressive variant. The aim of this study was to review clinico-pathologic features, and survival characteristics in a series of OGCRCs. MATERIALS AND METHODS: Five cases of OGCRCs of bladder were retrospectively reviewed. Clinical presentation, histomorphology, ancillary tests, treatment and follow-up data were retrieved and analyzed. RESULTS: All patients were adult males (age range 63-86 years) and presented with painless gross hematuria. All cases showed biphasic morphology with polygonal to epithelioid to spindle mononuclear cells (MCs) and scattered multinucleated osteoclast-like giant cells (OGCs). Background urothelium showed urothelial carcinoma in-situ (CIS) (4/5) and/or invasive urothelial carcinoma (UC) (2/5) and invasive high-grade papillary urothelial carcinoma (PUC) (2/5). MCs showed focal expression of at least one epithelial marker and focal/diffuse expression of urothelial markers. OGCs were positive only for histiocytic markers. Oncomine test showed presence of p53 mutation (p.R282W) in case 3. Pathologic stage was T1 (n = 3), T2b (n = 1) and T3a (n = 1). 2/5 patients died of disease within 3 years of diagnosis. CONCLUSIONS: OGCRC is an extremely rare and potentially aggressive malignant neoplasm of bladder. Most cases have associated conventional in-situ or invasive UC supporting undifferentiated or de-differentiated nature of this neoplasm. Surgery should be considered given the potential for aggressive behavior. However optimal treatment for OGCRCs remains unknown.

Clinicopathologic and molecular spectrum of testicular sex cord-stromal tumors not amenable to specific histopathologic subclassification.

A subset of testicular sex cord-stromal tumors (SCST), which includes neoplasms with mixed histology, cannot be classified into a specific histologic subtype. This study evaluated the clinicopathologic, immunophenotypic and molecular features of 26 SCST not amenable to specific classification by expert uropathologists. Median age at diagnosis was 43 years and median tumor size was 2.4 cm. Follow-up information was available for 18 (69%) patients, with evidence of an aggressive clinical course in 6 patients (4 alive with disease, 2 dead of disease 3 months and 6 months after orchiectomy). Microscopically, SCST not amenable to specific classification demonstrated monophasic epithelioid (9/26, 35%), monophasic spindle cell (5/26, 19%), and biphasic or mixed histology (12/26, 46%). One or more aggressive histopathologic features were seen in 11 cases. DNA sequencing was successful in 22 tumors. Pathogenic CTNNB1 and APC alterations were seen in 7 (33%) and 2 (10%) cases, respectively, with additional variants (e.g., CDKN2A, RB1, TP53, BRCA2) being identified in individual cases. Combined evaluation of morphology, sequencing data and beta-catenin immunohistochemistry resulted in reclassification of 6 (23%) tumors as Sertoli cell tumor, not otherwise specified. This was supported by comparing the methylation profiles of a subset of these tumors and those of typical Sertoli cell tumors. Additionally, a subset of 5 neoplasms (19%) with spindle cell or biphasic histology and SMA expression was characterized by hyperdiploid genomes with recurrent chromosomal gains and absence of driver mutations, possibly representing a distinct tumor type. The SCST that remained not amenable to specific histologic classification (15/26, 58%) were enriched for aggressive histologic features and malignant clinical behavior. In conclusion, this study demonstrated that a subset of testicular SCST that were originally not amenable to specific classification could be reclassified by combined evaluation of morphology, immunohistochemistry and molecular data.

Malignant juxtaglomerular cell tumor.

Juxtaglomerular cell tumors (JGCTs) are rare, typically benign neoplasms; only rare cases are clinically or histologically malignant. We herein report the histologic, immunophenotypic, and molecular features of a clinically unsuspected, diagnostically challenging case of malignant JGCT in a 23-year-old man. The diagnosis is confirmed with electron microscopy. The case is notable for its marked mitotic activity, which has not been previously reported in JGCTs, and novel finding of GATA3 immunohistochemical positivity.

Prostatic malakoplakia: clinicopathological assessment of a multi-institutional series of 49 patients.

Prostatic malakoplakia (MP) is rare, with only case reports and small series (< five patients) available in the literature. In this study we analysed an international multi-institutional series of 49 patients with prostatic MP to more clearly define its clinicopathological features. The median age was 67 years and the median serum prostate-specific antigen (PSA) was 7.5 ng/ml. MP was clinically manifest in most cases (28 of 45 patients with data available, 62%). Of 43 patients with detailed clinical history available, 21 (49%) had concurrent or metachronous malignancies (including prostate cancer). Diabetes or insulin resistance was present in 11 patients (26%). Additionally, three patients had a history of solid organ transplantation and one had HIV. Of note, six of 34 patients (18%) without concurrent prostate cancer had an abnormal digital rectal examination and/or lesions on magnetic resonance imaging (MRI) with prostate imaging reporting and data system (PIRADS) scores 4-5. The initial diagnosis was made on core biopsies (25 of 49, 51%), transurethal resection specimens (12 of 49, 24%), radical prostatectomies (10 of 49, 20%), Holmium-laser enucleation (one of 49, 2%) and cystoprostatectomy (one of 49, 2%). Tissue involvement was more commonly diffuse or multifocal (40 of 49, 82%). Von Kossa and periodic acid-Schiff stains were positive in 35 of 38 (92%) and 26 of 27 lesions (96%), respectively. Of note, two cases were received in consultation by the authors with a preliminary diagnosis of mesenchymal tumour/tumour of the specialised prostatic stroma. The present study suggests that prostatic MP is often associated with clinical findings that may mimic those of prostate cancer in a subset of patients. Moreover, MP may be found incidentally in patients with concurrent prostate cancer.

Fluorescent in-situ hybridization test performed on cell blocks is useful for establishing germ cell origin of metastatic tumors with unusual clinical presentation.

The majority of germ cell tumors (GCTs) are characterized by iso-chromosome 12p (i12p) abnormality. The aim of this study is to review the cytomorphologic features and analyze the utility of i12p fluorescent in-situ hybridization (FISH) test in diagnosing metastatic GCTs primarily evaluated by cytologic techniques in patients without prior history of GCTs. The laboratory information system was queried over a period of 10 years to search for cases where i12p FISH test was requested on cytology material. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on cell-blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, cytopathologic findings, and follow-up surgical resection data were reviewed and correlated. A total of three cases were identified, all men (age range 31-60 years). Cytologic diagnoses were favor metastatic embryonal carcinoma (Case 1, retroperitoneal fluid FNA), metastatic yolk sac tumor/YST (Case 2, lung mass FNA) and adenocarcinoma, likely representing a somatic-type malignancy (SM) arising from a preexisting GCT (Case 3, retroperitoneal mass FNA). This limited study demonstrated high sensitivity for detecting i12p abnormality by FISH test performed on cell blocks. The cytomorphology of extra-gonadal GCTs varies according to the histologic subtype. Sarcomatoid morphology of YST, SM or mixed GCTs further complicates cytology evaluation. FISH test for detection of i12p performed on cell-blocks is extremely useful in establishing germ cell origin of these metastatic GTCs with unusual cytomorphology and guides management in patients without prior history of GCTs.

Calyceal diverticula: Clinical, radiological and histopathological findings of an uncommon entity with presumed congenital origin.

Calyceal diverticula (CD) are relatively uncommon urologic conditions that generally follow an asymptomatic course and rarely require medical intervention. CD are thought to have a congenital origin due to abnormalities during the process of ureteral bud formation. Clinically and radiologically, they can mimic multiple neoplastic and non-neoplastic renal processes, with potentially relevant differences in the management of these patients. Symptoms are usually associated with the presence of stones, obstruction to the drainage of the diverticulum, large size, or secondary infection. In chronic cases, surgery might become necessary, creating an opportunity to examine the histopathological characteristics of this condition. Although these are benign in the majority of patients, some rare instances of malignancy arising from the CD have been reported. In this series, we addressed the clinical, radiological, and histopathological findings of CD.

Adenomatoid tumor of the testis: A rare case report.

Adenomatoid tumors (AT) are benign tumors commonly found in paratesticular tissues. However, intratesticular AT are rare. Clinically and radiologically, the AT of the testis imitates the malignant neoplasia of the testis. Here, we present a case of the intratesticular AT.

Absolute quantitative proteomics using the total protein approach to identify novel clinical immunohistochemical markers in renal neoplasms.

BACKGROUND: Renal neoplasms encompass a variety of malignant and benign tumors, including many with shared characteristics. The diagnosis of these renal neoplasms remains challenging with currently available tools. In this work, we demonstrate the total protein approach (TPA) based on high-resolution mass spectrometry (MS) as a tool to improve the accuracy of renal neoplasm diagnosis. METHODS: Frozen tissue biopsies of human renal tissues [clear cell renal cell carcinoma (n = 7), papillary renal cell carcinoma (n = 5), chromophobe renal cell carcinoma (n = 5), and renal oncocytoma (n = 5)] were collected for proteome analysis. Normal adjacent renal tissue (NAT, n = 5) was used as a control. Proteins were extracted and digested using trypsin, and the digested proteomes were analyzed by label-free high-resolution MS (nanoLC-ESI-HR-MS/MS). Quantitative analysis was performed by comparison between protein abundances of tumors and NAT specimens, and the label-free and standard-free TPA was used to obtain absolute protein concentrations. RESULTS: A total of 205 differentially expressed proteins with the potential to distinguish the renal neoplasms were found. Of these proteins, a TPA-based panel of 24, including known and new biomarkers, was selected as the best candidates to differentiate the neoplasms. As proof of concept, the diagnostic potential of PLIN2, TUBB3, LAMP1, and HK1 was validated using semi-quantitative immunohistochemistry with a total of 128 samples assessed on tissue micro-arrays. CONCLUSIONS: We demonstrate the utility of combining high-resolution MS and the TPA as potential new diagnostic tool in the pathology of renal neoplasms. A similar TPA approach may be implemented in any cancer study with solid biopsies.

Impact of biosolids amendment and wastewater effluent irrigation on enteric antibiotic-resistant bacteria - a greenhouse study.

Reuse of wastewater effluent and biosolids in agriculture is essential to sustainable water and nutrient resource management practices. Wastewater and biosolids, however, are reportedly the recipients, reservoirs, and sources of antibiotic-resistant enteric pathogens. While decay rates of fecal bacterial indicators in soil are frequently studied, very few studies have reported on the persistence of the antibiotic-resistant sub-populations. Little is known about how multi-drug resistance phenotypes of enteric bacteria in agricultural soil change over time. In this study, germinated carrot seeds were planted in soil that received biosolids amendment and/or wastewater effluent irrigation in a greenhouse setting. We quantified total and antibiotic-resistant fecal bacterial indicators (Escherichia coli and enterococci) weekly in soil and total E. coli at harvest (day 77) on carrots. Antibiotic susceptibility of 121 E. coli and 110 enterococci collected isolates were determined. E. coli or enterococci were not recovered from the soil without biosolids amendment regardless of the irrigation water source. After biosolids amendment, soil E. coli and enterococci concentrations increased more than 3 log10 CFU/g-TS within the first week, declined slowly over time, but stayed above the detection limit (0.39 CFU/g-TS) over the entirety of the study. No statistical difference was found between effluent wastewater or water irrigation in soil total and antibiotic-resistant E. coli and enterococci concentrations or carrots E. coli levels. Soil antibiotic-resistant E. coli and enterococci decayed significantly faster than total E. coli and enterococci. Moreover, the prevalence of multi-drug resistant (resistance to three or more antibiotics) E. coli declined significantly over time, while almost all collected enterococci isolates showed multi-drug resistance phenotypes. At harvest, E. coli were present on carrots; the majority of which were resistant to ampicillin. The survival of antibiotic-resistant enteric bacteria in soil and on harvested carrots indicates there are transmission risks associated with biosolids amendment use in root crops.

An artificial intelligence algorithm for prostate cancer diagnosis in whole slide images of core needle biopsies: a blinded clinical validation and deployment study.

BACKGROUND: There is high demand to develop computer-assisted diagnostic tools to evaluate prostate core needle biopsies (CNBs), but little clinical validation and a lack of clinical deployment of such tools. We report here on a blinded clinical validation study and deployment of an artificial intelligence (AI)-based algorithm in a pathology laboratory for routine clinical use to aid prostate diagnosis. METHODS: An AI-based algorithm was developed using haematoxylin and eosin (H&E)-stained slides of prostate CNBs digitised with a Philips scanner, which were divided into training (1 357 480 image patches from 549 H&E-stained slides) and internal test (2501 H&E-stained slides) datasets. The algorithm provided slide-level scores for probability of cancer, Gleason score 7-10 (vs Gleason score 6 or atypical small acinar proliferation [ASAP]), Gleason pattern 5, and perineural invasion and calculation of cancer percentage present in CNB material. The algorithm was subsequently validated on an external dataset of 100 consecutive cases (1627 H&E-stained slides) digitised on an Aperio AT2 scanner. In addition, the AI tool was implemented in a pathology laboratory within routine clinical workflow as a second read system to review all prostate CNBs. Algorithm performance was assessed with area under the receiver operating characteristic curve (AUC), specificity, and sensitivity, as well as Pearson's correlation coefficient (Pearson's r) for cancer percentage. FINDINGS: The algorithm achieved an AUC of 0·997 (95% CI 0·995 to 0·998) for cancer detection in the internal test set and 0·991 (0·979 to 1·00) in the external validation set. The AUC for distinguishing between a low-grade (Gleason score 6 or ASAP) and high-grade (Gleason score 7-10) cancer diagnosis was 0·941 (0·905 to 0·977) and the AUC for detecting Gleason pattern 5 was 0·971 (0·943 to 0·998) in the external validation set. Cancer percentage calculated by pathologists and the algorithm showed good agreement (r=0·882, 95% CI 0·834 to 0·915; p<0·0001) with a mean bias of -4·14% (-6·36 to -1·91). The algorithm achieved an AUC of 0·957 (0·930 to 0·985) for perineural invasion. In routine practice, the algorithm was used to assess 11 429 H&E-stained slides pertaining to 941 cases leading to 90 Gleason score 7-10 alerts and 560 cancer alerts. 51 (9%) cancer alerts led to additional cuts or stains being ordered, two (4%) of which led to a third opinion request. We report on the first case of missed cancer that was detected by the algorithm. INTERPRETATION: This study reports the successful development, external clinical validation, and deployment in clinical practice of an AI-based algorithm to accurately detect, grade, and evaluate clinically relevant findings in digitised slides of prostate CNBs. FUNDING: Ibex Medical Analytics.