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Introduction: The follow-up findings of patients who underwent prostate biopsy for prostate image reporting and data system (PIRADS) 4 or 5 multiparametric magnetic resonance imaging (mpMRI) findings and had benign histology were retrospectively reviewed., Methods: There were 190 biopsy-naive patients. Patients with at least 12 months of follow-up between 2012 and 2023 were evaluated. All MRIs were interpreted by two very experienced uroradiologists. Of the patients, 125 had either cognitive or software fusion MR-targeted biopsies with 4 + 8/10 cores. The remaining 65 patients had in-bore biopsies with 4-5 cores. Prostate-specific antigen (PSA) levels below 4 ng/mL were defined as PSA regression following biopsy. PIRADS 1-3 lesions on new MRI images were classified as MRI regression., Results: Median patient age and PSA were 62 (39-82) years and six (0.4-33) ng/mL, respectively, at the initial work-up. During a median follow-up period of 44 months, 37 (19.4%) patients were lost to follow-up. Of the remaining 153 patients, 82 (53.6%) had persistently high PSA. Among them, 72 (87.8%) had repeat mpMRI within 6-24 months which showed regressive findings (PIRADS 1-3) in 53 patients (73.6%) and PIRADS 4-5 index lesion persistence in 19 cases (26.4%). The latter group was recommended to have rebiopsy. Of these 19 patients, 16 underwent MRI-targeted rebiopsy. Prostate cancer was diagnosed in six (37.5%) patients and of these four (25%) were clinically significant (>Grade Group 1). Totally, clinically significant prostate cancer was detected in 4/153 (2.6%) patients followed up., Conclusion: Patients should be warned against the relative relaxing effect of a negative biopsy after identification of PIRADS 4-5 index lesion. While PSA decrease was observed in many patients during follow-up, persistent MRI findings were present in nearly a quarter of patients with persistently high PSA. A rebiopsy is warranted in these patients, with significant prostate cancer diagnosed in a quarter of patients with rebiopsy., (© 2024 Wiley Periodicals LLC.)

A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of these were also investigated with next-generation sequencing with a 174 genes panel. The patients were 5 males and 3 females, with a mean age of 64.6. All tumors were intrahepatic except for one perihilar that protruded into soft tissues. The mean size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern that closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules, and occurring in the background of adenofibromatous lesions. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures, one had areas transitioning to intraductal tubulopapillary neoplasm, and 3 cases harbored more conventional small-duct CCA foci. In those 3 cases, both the tubulocystic and conventional CCA components were investigated by next-generation sequencing separately, and they shared the molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A , BAP1 , and PBRM1 , and the actionable FGFR2-MCU fusion gene. In the limited follow-up, all but one were alive and free of disease after surgical resection. In conclusion, we described a distinct entity of CCA with specific histo-molecular features, for which we propose the designation of tubulocystic carcinoma of bile ducts., Competing Interests: Conflicts of Interest and Source of Funding: A.S.: consulting and speaker bureau from: MSD, Incyte, Medica s.r.l., NTP. C.L.: consulting and speaker bureau from: MSD, Medica s.r.l., NTP. For the remaining authors, none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma)., Competing Interests: Conflicts of Interest and Source of Funding: O.B. has been supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the performance of computed tomography (CT) in the local staging of colon cancer in different segments, with emphasis on parameters that have been found to be significant for rectal cancer, namely, extramural venous invasion (EMVI) and tumor deposits (TDs)., Methods: CT and pathology data from 137 patients were independently reviewed by radiology and pathology teams. The performance of CT in categorizing a given patient into good, versus poor prognostic groups was assessed for each segment, as well as the presence of lymph nodes (LNs), TDs and EMVIs. Discordant cases were re-evaluated to determine potential sources of error. Elastic stain was applied for EMVI discordance., Results: The T staging accuracy was 80.2%. For T stage stratification, CT performed slightly better in the left colon, and the lowest accuracy was in the transverse colon. Under-staging was more common (in 12.4%), and most of the mis-staged cases were in sigmoid colon. According to the first comprehensive correlative analysis, the sensitivity, specificity, and accuracy of CT for detecting TDs were found to be 57.9%, 92.4%, 87.6%, respectively. These figures were 44.7%, 72.7%, and 63.5% for LN, and 58.5%, 82.1% and 73% for EMVI. The detection rate was better for multifocal EMVI. The detection rate was also comparable (although substantially underestimated) for LNs, with the half of the LNs missed by CT being < 5 mm. Four patients that were classified as TD by CT, disclosed to be LNs by pathology. Correlative analysis led to refinement of the pathology criteria, with subsequent modifications of the initial reports in 13 (9.5%) patients., Conclusion: Overall, CT performed well in the evaluation of colon cancer, as did TD and EMVI. It is advisable to include these parameters in CT-based staging. Radiologists should be aware of the pitfalls that occur more commonly in different segments., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction and Objectives: To investigate the additive role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) independent from multiparametric magnetic resonance imaging (mpMRI) and clinical-pathological parameters to predict pathological upgrading in patients with ISUP grade group (GG) 1 prostate cancer (PCa) at prostate biopsy., Materials and Methods: A total of 41 patients who underwent robotic radical prostatectomy (RP) for GG1 disease at prostate biopsy with preoperative PSMA PET/CT and mpMRI images available for central review were included in the study. Univariate and multivariate logistic regression analyses were performed to determine the independent predictors of pathological upgrading (GG ≥ 2)., Results: Final RP pathology revealed upgrading in 26 patients (65.9%); to GG 2 disease in 25 cases and GG 4 disease in one case. International Society of Urological Pathology (ISUP) upgrading rates for prostate imaging-reporting and data system (PIRADS)-5, PIRADS-4, and PIRADS ≤ 3 lesions were 78%, 74%, and 38%, respectively. Fourteen out of 15 (93.3%) patients with an SUVmax ≥ 5.6 and all patients with an SUVmax ≥ 6.5 (n = 10) had pathological upgrading. The upgrading rate in patients with SUV < 5.6 was 46.2% (12/26). Intraprostatic SUVmax ≥ 5.6 was found as the only independent predictor of pathological upgrading in multivariate analysis., Conclusion: High prostatic PSMA uptake was found to be a very reliable predictor of pathological upgrading, but low PSMA uptake cannot exclude pathological upgrading. Intraprostatic PSMA uptake along with previously known mpMRI and biopsy-related parameters should be considered when making a treatment decision in patients with GG1 PCa at prostate biopsy., (© 2023 Wiley Periodicals LLC.)

Purpose: In this retrospective study, we aimed to determine the safe surgical limit for excision of pterygium tissue. Therefore, we aimed to prevent excessive or incomplete normal conjunctival tissue excision during surgery in the coming years., Methods: Autografted pterygium surgery was performed between January 2015 and April 2016, and the excised pterygium tissue was examined histopathologically. The files of 44 patients, who had not previously undergone any ocular surgery, who did not have an inflammatory disease and who continued to be checked for at least 1 year, were retrospectively examined. The distance (P-DSEM) from the excised pterygium tissue to the surgical excision margin was measured by a pathologist. Postoperative recurrence rates were evaluated according to this value. In this way, the clean surgical margin was determined., Results: The mean age of the participants was 44.77 ± 12.70, and the mean follow-up time was 55.61 ± 16.38 months. Recurrence developed in 5 out of 44 patients (11.4%). The average recurrence duration was 51 ± 13.87 days. Distance to the average surgical margin was 3.88 ± 0.91 mm. The surgical distances of 5 patients with recurrence were 2, 2.5, 2, 3, and 3 mm, respectively. It was determined that recurrence was less as the distance (P-DSEM) from the tissue to the surgical excision margin increased (p = 0.001)., Conclusions: We found that the recurrence rate in pterygium surgery was linked to the clean surgical margin. When planning pterygium surgery, we believe that determining the amount of tissue to be excised before surgery will reduce recurrence rates., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

"Eosinophilic cholecystitis" has been an elusive concept. Around 1050 consecutive cholecystectomies with chronic (CC, n = 895), subacute (SAC, n = 100), and acute cholecystitis (AC, n = 55) were reviewed for eosinophilic infiltration. Eosinophilic hot spots (>40 eosinophils/HPF) were seen in 63% of SAC and 35% of AC (vs. 6% of CC, p < 0.001). Eosinophils were mostly encountered in areas of wall thickening, revealing edema with early collagenization and young tissue-culture-type fibroblasts. However, in ten chronic cholecystitis patients (<1%), prominent eosinophilia with eosinophil-rich foci (>100 eosinophils/HPF) was noted. These ten cases, classified as "eosinophilic cholecystitis", were analyzed further: The patients were relatively young (mean age = 43 years), with a 9:1 female:male ratio. None had blood eosinophilia/eosinophilia syndromes. Although one had ulcerative colitis, others did not have any autoimmune diseases. The mean gallbladder wall thickness was 3.5 mm (vs. 4.2 mm in ordinary CC). In conclusion, eosinophils are a part of especially subacute injuries in the gallbladder. They are typically condensed in the areas of healing and appear to signify a distinctive state of injury in which there are erosions leading to slow/sustained exposure of the mural tissues to the bile contents that induce chemical injury/recruit eosinophils. Eosinophilic cholecystitis is a very uncommon occurrence and appears to be an exaggerated response in allergic patients who are prone to recruit eosinophils in reaction to injury.

Adenosine deaminase (ADA) deficiency is one of the most prevalent forms of severe combined immunodeficiency and results in the accumulation of toxic substrates which creates a systemic metabolic disease. It predisposes patients to the development of malignancies, most commonly lymphoma. We report an 8-month-old infant with ADA deficient severe combined immunodeficiency who developed progressive liver dysfunction and hepatocellular carcinoma after successful hematopoietic stem cell transplantation. This is the first case report of an ADA-deficient patient who presented with hepatocellular carcinoma and gives an insight into the complex etiology that can lie behind liver dysfunction in these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectıvely. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements ın stagıng and oncologıc outcomes may also be seen ın intermediate- and high-risk patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up-regulated phosphoproteins are associated with protein synthesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, minocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment., Competing Interests: Conflict of Interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as "hepatobiliary cystadenoma." II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as "cystadenoma/carcinoma." Defined by OTS, MCNs (the true "hepatobiliary cystadenoma/carcinoma") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term "cystadenoma/cystadenocarcinoma" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The cost-effectiveness and low rate of inadequate sampling with the use of rapid on-site evaluation (ROSE) along with endobronchial ultrasonography (EBUS) is well established. Our aim in this study was to evaluate the correlation of ROSE during EBUS and final cytologic diagnosis and also to see if ROSE might predict the subtype of lung cancer., Patients and Methods: All consecutive subjects who attended our clinic between January 2016 and January 2019 for the evaluation of pathologic mediastinal and/or hilar lymph nodes (LNs)/mass using EBUS were enrolled into our prospective study. ROSE was performed in the same operating room with EBUS. ROSE results during EBUS were recorded. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ROSE compared with the final cytologic diagnosis were evaluated., Results: We enrolled 684 LN/mass lesions belonging to 328 patients into this study. When we compared ROSE results and final cytologic diagnosis, these procedures agreed on 91.6% of the LNs (P<0.001). The sensitivity of ROSE and final cytologic diagnosis for granulomatous inflammation was 72.5%, and for lung cancer, it was 89.2% (P<0.001). The sensitivity of ROSE for the adenocarcinoma subtype of lung cancer was 67.7%, and it was 70% for small cell lung cancer., Conclusion: ROSE may help to recognize non-small cell lung cancer during EBUS, especially the adenocarcinoma subtype of lung cancer, which will help ensure having sufficient material for molecular analysis., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were <=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases <=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Objective: To determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations., Material and Method: Fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed., Results: Five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p > 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease., Conclusion: This is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response.

Clear cell renal cell carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified four putatively secreted biomarker candidates, namely, PLOD2, FERMT3, SPARC, and SIRPα, as highly expressed proteins that are not affected by intratumor and intertumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of patients with ccRCC, making it a promising marker for the detection of the disease in body fluids. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared with cluster 2 tumors. Moreover, among the most significant clustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC. IMPLICATIONS: Our in-depth quantitative proteomics analysis of ccRCC tissues identifies the putatively secreted protein SPARC as a promising urine biomarker and reveals two molecular tumor phenotypes., (©2021 American Association for Cancer Research.)

Background: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function., Methods: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning., Results: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05)., Conclusion: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels., (© 2021. The Author(s).)

Background: To evaluate the additive role of Ga-68 PSMA PET as a primary staging tool in patients bearing prostate cancer in single PIRADS 4 or 5 index lesions., Methods: Eighty-one biopsy-naive patients with preoperative mpMRI and Ga-68 PSMA PET who underwent radical prostatectomy (RP) were evaluated retrospectively. Forty-nine patients had PIRADS 4 and 32 had PIRADS 5 index lesions. The localization, grade, and volumetric properties of dominant (DT) and non-dominant tumors (NDT) in RP were compared to the index lesions of mpMRI and Ga-68 PSMA PET., Results: The median age and PSA level were 62 (IQR; 59-69) years and 7 (IQR; 2-8) ng/ml, respectively. Ga-68 PSMA PET detected DTs in 100% of the patients including 13 patients in whom mpMR failed. In 45 patients an NDT was reported in RP. Ga-68 PSMA PET accurately detected NDT in 24 of 45 (53.3%) patients. Six patients (12.2%) in PIRADS 4 and 8 (25%) in PIRADS 5 group showed upgrading. In PIRADS 4, Ga-68 PSMA PET localized DT in all patients with upgraded tumors whereas mpMRI missed exact location in 2 of 6 (33.3%). In PIRADS 5 both mpMRI and Ga-68 PSMA PET accurately located all DTs. Overall detection rates of extracapsular extension (ECE) and seminal vesicle invasion (SVI) by mpMRI were 51.1% and 53.8%, respectively. Ga-68 PSMA PET detected ECE and SVI in 27.9% and 30.7%, respectively. When mpMRI and Ga-68 PSMA PET were used in combination detection rates of ECE and SVI increased to 65.1 and 61.5%. Ga-68 PSMA PET-detected six of ten patients with positive lymph nodes whereas mpMRI could not identify any., Conclusions: Ga-68 PSMA PET has a better diagnostic accuracy in detecting DT, NDT, upgrading, adverse pathology in patients with PIRADS 4 index lesions. However, mpMRI better predicted ECE and SVI than Ga-68 PSMA PET.

Background: Results from prospective trials have shown higher accuracy of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in detection of lymph node metastasis (LNM) compared to conventional imaging., Objective: To evaluate the accuracy of 68 Ga-PSMA-11 PET/CT for LNM detection in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND)., Design, Setting, and Participants: Between June 2014 and November 2020, 96 patients with 68 Ga-PSMA PET/CT for primary staging underwent RP and extended PLND., Outcome Measurements and Statistical Analysis: The results from 68 Ga-PSMA PET/CT were compared with histologic data from primary PLND in 96 patients. All 68 Ga-PSMA PET/CT scans were centrally reviewed., Results and Limitations: Of 96 patients, 15.6% (n = 15) harbored LNMs. The median prostate-specific antigen at 68 Ga-PSMA PET/CT was 8.0 ng/ml (interquartile range 5.5-11.7). The majority of patients had intermediate- (52.1%) or high-risk disease (41.7%). Biopsy grade group 4 and 5 was present in 22.9% and 15.6%, respectively. The 68 Ga-PSMA PET/CT scans identified eight of 15 patients (53.3%) as LN-positive (true positive). The calculated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68 Ga-PSMA PET/CT in the detection of LNM were 53.3%, 98.8%, 88.9%, 92.0%, and 91.7%, respectively. The per-patient sensitivity and specificity in the detection of LNMs larger than 2 mm were 61.5% and 98.8%, respectively. The main limitation is the retrospective design of the study., Conclusions: 68 Ga-PSMA PET/CT is accurate in lymph node staging and the results support its use for primary staging of prostate cancer., Patient Summary: We compared prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) findings with histopathology results after extended lymph node dissection and showed that it is accurate in detecting lymph node metastases. Our results support the use of PSMA PET/CT for primary staging of prostate cancer., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: The nature and clinicopathologic associations of Löwenstein-Buschke disease are unclear., Materials and Methods: 78 anal condylomatous lesions (≥2 cm) were analyzed. Cases were classified based on size as "medium-large"(2-5 cm, n=59), "large" (5-10 cm, n=13) and "giant" ( > 10 cm, n=6)., Results: Patients were predominantly males (male/female=70/8). The mean age was 38 years (range:20-66). Two distinct lining types were recognized: 1) Epidermal type, typically lacking overt koilocytotic change, with associated invasive carcinoma in 8%; 2) Mucosal type, often manifesting koilocytotic change, with associated invasive carcinoma in 21%. Three types of high-grade dysplasia were discerned: 1) Basaloid, 8/9 showing high-grade dysplasia/carcinoma in-situ but non-invasive lesions; 2) Keratinizing, innocuous-appearing, but 5/6 was associated with invasion; 3) Giant cell, showing scattered individual bizarre cells, with 3/5 showing invasive carcinoma. Overall, invasion was found in 14% of the cases. The bulbous, broad-based destructive pattern characterizing verrucous carcinomas of the upper aerodigestive tract was not observed. A statistically significant trend existed between the incidence of invasion and size: 8.5% for medium-large, 23% for large, and 50% for giant (p=0.02). There was no discernable trend in the depth of invasion relative to condyloma size., Conclusions: Our findings suggest that Löwenstein-Buschke lesions are mega versions of conventional condyloma. Being verrucoid, large and minimally invasive, they can be conceptually regarded as a form of verrucous carcinoma, but they do not display the histologic characteristics of verrucous carcinoma defined in the aerodigestive tract. They exhibit two types of linings: the mucosal type that often shows koilocytotic changes, and the epidermal type that can be difficult to recognize in biopsies. These lesions may be associated with invasive carcinoma, albeit limited in amount.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm seen in children and young adults, usually manifested by involvement of abdominal serosa. Here, we present an unusual case of primary DSRCT of kidney., Case Presentation: The patient was an 8-year-old girl with a large renal mass which was confused with primitive neuroectodermal tumor (PNET) in the needle biopsy. The tumor had a variegated histology revealing frequent pseudo-rosette formations, pseudopapillary architecture, rhabdoid, clear or pleomorphic cells in addition to typical small round cell morphology and desmoplasia. It showed immunohistochemical features of DSRCT, and EWSR1 re-arrangement., Conclusions: Proffering this diagnosis is particularly difficult for tumors of viscera because of the incognizance of the entity in these locations. Moreover, DSRCT is a great mimicker and may get easily confused with more common kidney malignancies of childhood such as Wilms tumor, PNET/EWS, rhabdoid tumor, clear cell sarcoma, and other small round cell tumors as well as renal cell carcinomas. The distinction is critical as the accurate therapeutic approach will require correct diagnosis.

Objectives: To assess the most optimal multi-parametric magnetic resonance imaging sequence (Mp-MRI) in determining pathological length of capsular contact (LCC) for the diagnosis of prostate cancer extraprostatic extension (EPE)., Methods: 105 patients with prostate cancer who underwent Mp-MRI of prostate prior to radical prostatectomy were enrolled in this retrospective study. LCC was determined from T2-weighted images (T2WI), Apparent Diffusion Coefficient (ADC) map, dynamic contrast-enhanced MRI (DCE-MRI) separately by two blinded radiologists. The LCCs in patients with and without EPE were compared with Mann Whitney-U test. The relationship between pathological LCC and the LCC that was measured from each Mp-MRI sequences were calculated by using Spearman test. The ability of all individual Mp-MRI sequences in determining pathological LCC was calculated by drawing receiver operator characteristic (ROC) curves. The diagnostic accuracy of LCC based on each MRI sequences for EPE diagnosis was also calculated with ROC curve analysis., Results: The patients with EPE had longer median LCC than patients without EPE for each Mp-MRI sequences and for both readers. In addition, the LCC showed a broader overlapping between patients with and without EPE on ADC map (reader-1, p = 0.01; reader-2, p = 0.01) when compared with T2WI (reader-1, p = 0.002; reader-2, p = 0.001) and DCE-MRI (reader-1, p = 0.001; reader-2, p = 0.001). LCC based on DCE-MRI showed the strongest correlation with pathological LCC. The area under the curve (AUC) based on LCC was higher when using the DCE-MRI (reader-1: 0.874, p = 0.030; reader-2: 0.862, p = 0.02) than when using T2WI and ADC map in predicting pathological LCC for both readers. While the LCC based on ADC map showed poor diagnostic accuracy, LCC based on T2WI and DCE-MRI had fair diagnostic accuracy for EPE diagnosis., Conclusion: The contact between prostate tumor and capsule seems to be a useful and objective parameter for evaluating the EPE of prostate cancer with Mp-MRI. More specifically, LCC based on DCE-MRI has highest correlation with pathological LCC and has better ability to predict pathological LCC when compared with other Mp-MRI sequences. However, the performance of LCC based on T2WI and DCE-MRI was similar for EPE diagnosis. It seems measurement of LCC from DCE-MRI and measurement of LCC from T2WI does not show any difference in clinical EPE assessment., (Copyright © 2019 Elsevier B.V. All rights reserved.)