Enhancing Prostate Tumor Biobanking Reliability with Improved Sampling Technique and Histological Characterization.

Acquiring fresh and well-characterized tumor tissue samples is critical for conducting high-quality "omics" studies. However, it can be particularly challenging in the context of prostate cancer (PC) due to the unique nature of this organ and the high heterogeneity associated with this tumor. On the other hand, histopathologically characterizing samples before their storage without causing significant tissue alterations is also an intriguing challenge. In this context, we present a new method for acquiring, mapping, characterizing, and micro-dissecting resected prostate tissue based on anatomopathological criteria. Unlike previously published protocols, this method reduces the time required for histopathological analysis of the prostate specimen without compromising its structure, which is crucial for assessing surgical margins. Furthermore, it enables the delineation and micro-macro dissection of fresh prostate tissue samples, with a focus on histological tumor areas defined by pathological criteria such as Gleason score, precursor lesions (high-grade prostatic intraepithelial neoplasia - PIN), and inflammatory lesions (prostatitis). These samples are then stored in a Biobank for subsequent research analyses.

Bladder cancer patients have increased NETosis and impaired DNaseI-mediated NET degradation that can be therapeutically restored in vitro.

Background: Neutrophils, key players of the immune system, also promote tumor development through the formation of neutrophil extracellular traps (NETs) in a process called NETosis. NETs are extracellular networks of DNA, histones and cytoplasmic and granular proteins (calprotectin, myeloperoxidase, elastase, etc.) released by neutrophils upon activation. NETs regulate tumor growth while promoting angiogenesis and invasiveness, and tumor cells also stimulate NETosis. Although NETosis seems to be increased in cancer patients, an increase of NETs in plasma may also be mediated by an impaired degradation by plasma DNaseI, as evidenced in several immunological disorders like lupus nephritis. However, this has never been evidenced in bladder cancer (BC) patients. Herein, we aimed to evaluate the occurrence of increased NETosis in plasma and tumor tissue of BC patients, to ascertain whether it is mediated by a reduced DNaseI activity and degradation, and to in vitro explore novel therapeutic interventions. Methods: We recruited 71 BC patients from whom we obtained a plasma sample before surgery and a formalin-fixed paraffin embedded tumor tissue sample, and 64 age- and sex-matched healthy controls from whom we obtained a plasma sample. We measured NETs markers (cell-free fDNA, calprotectin, nucleosomes and neutrophil elastase) and the DNaseI activity in plasma with specific assays. We also measured NETs markers in BC tissue by immunofluorescence. Finally, we evaluated the ability of BC and control plasma to degrade in vitro-generated NETs, and evaluated the performance of the approved recombinant human DNaseI (rhDNaseI, Dornase alfa, Pulmozyme®, Roche) to restore the NET-degradation ability of plasma. In vitro experiments were performed in triplicate. Statistical analysis was conducted with Graphpad (v.8.0.1). Results: NETosis occurs in BC tissue, more profusely in the muscle-invasive subtype (P<0.01), that with the worst prognosis. Compared to controls, BC patients had increased NETosis and a reduced DNaseI activity in plasma (P<0.0001), which leads to an impairment to degrade NETs (P<0.0001). Remarkably, this can be therapeutically restored with rhDNaseI to the level of healthy controls. Conclusion: To the best of our knowledge, this is the first report demonstrating that BC patients have an increased NETosis systemically and in the tumor microenvironment, in part caused by an impaired DNaseI-mediated NET degradation. Remarkably, this defect can be therapeutically restored in vitro with the approved Dornase alfa, thus Pulmozyme® could become a potential therapeutic tool to locally reduce BC progression.

Cold loop polypectomy perforation of a tiny colon polyp.

We report the case of a 61-year-old woman having corticoid treatment with corticosteroids for polyarthralgia, who underwent a post-polypectomy surveillance colonoscopy, identifying a 5-mm diameter, flat-elevated polyp in the proximal transverse colon (Paris 0-IIa).

Evaluation of the optical criteria for sessile serrated lesions of the colon: A prospective study on a colorectal cancer screening population.

Background and study aims We aimed to describe the presence and combination of Hazewinkel's optical diagnosis (OD) criteria for sessile serrated lesions (SSL), determining which lesion characteristics increase the probability of a correct OD, with a focus on diminutive lesions. Patients and methods This was a prospective study describing the presence of Hazewinkel's OD criteria for SSL in lesions found in consecutive CRC screening colonoscopies. The presence of each OD criterion and their diagnostic combinations in SSL, related to the lesion's NBI International Colorectal Endoscopic (NICE) classification category, size, and location, were described. The presence of two or more optical criteria was considered diagnostic of SSL. The OD was compared to pathology as the gold standard. Results Seventy-nine SSLs (5.6 %) were diagnosed. Cloud-like appearance was the most prevalent OD criterion (35, 44.3 %). OD criteria were more frequently identified in NICE type 1, ≥ 10 mm, and proximal lesions. Only 26 SLLs fulfilled the OD criteria (sensitivity 32.9 %, 95 % CI 29.1 %-36.7 %). The sensitivity for diminutive SSL was 14.7 %, (95 % CI 11.9 %-17.6 %). Eighty-five lesions were optically diagnosed as SSL. However, only in 26 SSL was this the definitive diagnosis (positive predictive value 30.6 %, 95 % CI 26.9 %-34.3 %). Size > 5 mm and proximal location increased the probability of a correct diagnosis. The overall accuracy of the optical criteria was 92.0 % (95 % CI, 89.8 %-94.2 %). Conclusions The Hazewinkel's optical criteria are not reliable for a positive diagnosis of SSL, particularly for diminutive lesions.

Tumor Budding: Prognostic Value in Muscle-invasive Bladder Cancer.

OBJETIVES: To assess if "tumor budding" (TB) behaves as a poor prognostic factor in muscle-invasive bladder carcinoma (MIBC). TB is the presence of tumor cells isolated or in small groups of fewer than 5 cells located at the tumor invasion front. MATERIAL AND METHODS: Retrospective study of 106 patients with MIBC who underwent radical cystectomy. A cytokeratin AE1/AE3 immunostaining was applied to identify and quantify TB by the "hot-spot" method. The variables evaluated were: age, gender, Tumour, Node, Metastasis Classification (TNM) stage, associated Carcinoma in situ, differentiation degree, tumor size, tumor location, lymphatic, venous or perineural invasion, p53, Ki67, molecular subtype (basal/luminal) and chemotherapy. Main variables were overall and cancer-specific survival. RESULTS: The mean follow-up time was 47 ± 46.45 months. The mean TB count was 32.3 ± 25.9 "buds." The ROC curve established 14 "buds" as the cut-off point: the median survival rate for the "low-grade TB" group (≤14 "buds") was 69.5 months, and for the "high-grade TB" group (>14 "buds") was 18.5 months (P= .003). In the multivariate analysis, independent predictive variables regarding mortality were: age, TB, and TNM stage. Patients with more than 14 "buds" had 2.27 times more risk of mortality, 95%CI:1.19-4.34, P = .013. In addition, the risk of mortality rises progressively as the number of "buds" increases, at a rate of 2% per "bud." CONCLUSION: According to our results, TB becomes an independent predictor factor for cancer-specific mortality in MIBC, with a cut-off point of 14 "buds."

Immunohistochemical expression of Ki-67, Cyclin D1, p16INK4a, and Survivin as a predictive tool for recurrence and progression-free survival in papillary urothelial bladder cancer pTa / pT1 G2 (WHO 1973).

OBJECTIVES: To investigate the expression of several immunohistochemical (IHC) markers and their predictive ability for the recurrence-free and progression-free survival of papillary urothelial bladder cancer (UBC) pTa/pT1 G2 (WHO 1973) compared to classical anatomo-clinical variables using a multidimensional analysis. MATERIALS AND METHODS: A population-based cohort of 213 primary stage UBC (pTa/pT1) G2 (WHO 1973) was evaluated by classic anatomopathological variables and characterized by immunohistochemistry (23 IHC markers, representative of different oncogenic pathways). The most important variables as a predictor of recurrence-free and progression-free survival were selected using multidimensional statistical models, such as random survival forests and least absolute shrinkage and selection operator (. Recurrence and progression-free survival of the previously selected variables were also calculated. RESULTS: Mean follow-up was 58 ± 33.5 months. Recurrence and progression rates were 54.5% (n = 116) and 17,4% (n = 37), respectively. The most influential variables in the low recurrence-free survival were in order: number of resected tumors, high expression of Ki67 (>10%), Cyclin D1 (>10%), and low cytoplasmic staining of p16INK4a. Regarding low progression-free survival, the most important variables were Ki67 (>15%), multicentric tumor arrangement and Survivin nuclear expression (>20%). Kaplan-Meier and cox-regression model analyses showed that the variables selected by multidimensional models were able to discriminate the clinical outcome. CONCLUSIONS: Ki67 index is the most useful IHC marker, since it can improve the prediction of both recurrence and progression-free survival in papillary UBC pTa/pT1 G2 (WHO 1973). There are other markers, whose utility is specific to recurrence-free survival, such as Cyclin D1 and p16INK4a or in progression-free survival, such as Survivin.

[Tubulocystic renal cell carcinoma. A rare entity in neoplastic renal pathology]. / Carcinoma tubuloquístico. Una entidad infrecuente en la patología tumoral renal.

Tubulocystic renal carcinoma is an uncommon neoplasm. We present a case of a patient presenting with multiple renal colic. A nodular cystic lesion was an incidental sonographic finding which increased in size during subsequent follow-ups. The patient underwent radical nephrectomy and tubular renal carcinoma was diagnosed histopathologically and immunohistochemically.

Percentage of cancer in prostate biopsies as prognostic factor for staging and postoperative biochemical failure after radical prostatectomy.

OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. RESULTS: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.

[Idiopathic granulomatous orchitis: pathologic study of one case]. / Orquitis idiopática granulomatosa: estudio anatomopatológico de un caso.

OBJECTIVE: To report one case of idiopathic granulomatous orchitis, an extremely rare disease, in a 76-year-old patient. METHODS/RESULTS: The pathology department received a testicle with the clinical/radiological diagnosis of testicular tumor. The pathologic study showed absence of neoplasias and presence of morphological findings compatible with idiopathic granulomatous orchitis. CONCLUSIONS: The idiopathic granulomatous orchitis is an entity of unknown etiology, clinically or ultrasonographically not distinguishable from testicular neoplasias, the diagnosis of which is made after orchiectomy.

[Comparative study of P 53, Bcl-2, and C-erbB-2 expression in low-grade papillary bladder tumors]. / Estudio comparativo de la expresión de p53, Bcl-2 y C-erbB-2 en neoplasias papilares vesicales de bajo grado.

OBJECTIVE: To study the prognostic value of p53, bcl-2 and c-erbB-2 immunoexpression in predicting tumor relapses in low-grade papillary bladder neoplasms. METHODS: In all patients a complete transurethral resection of the lesion was performed. All the material was formalin-fixed and paraffin-embedded. At the immunohistochemical level, the following monoclonal antibodies were utilized: p53 (clone DO7), bcl-2 (clone 124) and c-erbB-2 (clone CB11). In order to predict tumor relapses during follow-up, a study of specificity, sensitivity and predictive positive value (PVP) and negative was designed. In univariate statistical studies, the following tests were utilized: Chi-square, Kaplan-Meier estimates and Cox logistic regression. RESULTS: Mean follow-up was 76.6 months (38 to 168). In recurrence prediction, p53 expression showed a high specificity (99%) as well as a high PPV (96%). Regarding bcl-2 and c-erbB-2 immunoexpression, both specificity (65% and 72%) and PPV (61% and 72%) were also high, although these percentages were lower than those obtained for p53 expression. The combined analysis of p53 and bcl-2 indicated that bcl-2 immunoexpression in non-basal cells of the urothelium could be independent of p53, although the number of cases showing this particular expression pattern is not high enough to perform an accurate statistical analysis. Otherwise, histologic grade demonstrated higher sensitivity (64%) and lower specificity (40%) than the immunohistochemical markers. In univariate studies, p53 showed an intense statistical correlation with relapse-free interval (RFI) and prediction of tumor recurrences during follow-up (p < 0.001), whereas the expression of bcl-2 (p = 0.065) was nearly correlated with RFI (p = 0.065). In contrast, expression of c-erbB-2 did not show statistical correlation (p = 0.112). CONCLUSIONS: In our study, individual and combined analysis of p53 and bcl-2 immunoexpression have demonstrated to be useful in predicting tumor recurrences and RFI in low-grade bladder lesions.