Coordinated Increased Expression of Cyclooxygenase2 and Nuclear Factor κB Is a Steady Feature of Urinary Bladder Carcinogenesis

Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-κB immunohistochemical expression in a large series of normal epithelium and bladder carcinomas. Methods. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas). Results. COX-2 expression is increased in the cytoplasm of bladder cells, during loss of cell differentiation (rs = 0.61, P-value < .001) and in muscle invasive carcinomas (P-value < .001). A strong positive association between tumor grade and nuclear expression of NFκB has been established. A positive correlation between COX-2 and nuclear NFκB immunoreactivity was observed. Conclusions. The possible coordinated upregulation of NFκB and COX-2, during bladder carcinogenesis, indicates that agents inhibitors of these two molecules may represent a possible new treatment strategy, by virtue of their role in bladder carcinogenesis

Rapture of renal angiomyolipoma during pregnancy: a case report

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Morphological expression - cross talk - of estrogen receptors (ERβ) and NFkB, during carcinogenesis of transitional cell epithelium of urinary bladder: Potential chemopreventing strategies

Backround: Bladder cancer is the forth most common malignancy among men in the Western World following prostate, lung and colon cancer. Epidemiological and molecular data support the possible role of ERβ and NFκB between the two collateral processes providing evidence for target specific chemopreventive strategies. ERβ promotes cellular differentiation and restriction of inflammation. Nuclear receptor coregulators provide a great level of sophistication in the dynamic process of transcriptional regulation. The transcriptional coactivator p300 is a ubiquitous nuclear protein and transcriptional cofactor with intrinsic acetyltransferase activity. NCoR is a protein that contain distinct functional domains responsible for interaction with NRs and activation of HDAC proteins ultimately resulting in targeted repression of transcription COX-2 an enzyme often induced in neoplasmatic conditions perpetuates the chronic inflammatory state in the epithelium and its microenvironment by means of prostaglandin synthesis. Materials and Methods: In our retrospective study we included 111 consecutive patients (74 males and 37 females) aged 23-90 years (mean 70±10) diagnosed with TCC of the bladder by either biopsies transurethral resection of bladder tumor or radical cystectomies between 2000 and 2002 from the Urological Department of Urology of University Hospital of Patras. Greece None of the patients had received any preoperative intravesical therapy. Bladder tumors were graded and staged according to the World Health Organization (WHO) grading. Paraffin section immunohistochemistry was utilized and relative expression was estimated in intracellular compartments, intraepithelial layers and histologic categories NFκΒ (p65 subunit) demonstrated mixed subcellular presence COX-2 cytoplasmic whereas ERβ, p300 and NCoR staining patterns were nuclear NFκB and COX-2 were constantly upregulated as tumorigenesis progressed. Results: NFκB, COX-2 and p300 expression correlated positively with progression of carcinogenesis suggesting a potential involvement in bladder tumorigenesis. On the contrary ERβ and NCoR were severely diminished in cancer compared to normal epithelium and they were affected by tumor Grade. Conclusions: The inhibition of ERβ in combination with the antiapoptotic properties of NFκB may contribute to the pathogenesis of TCC. Selective ERβ and NCoR agonist and agents inhibitors of NFκB, COX-2 and p300 may represent a possible new treatment strategy by virtue of their role in bladder carcinogenesis.Στόχος: Μορφολογική εκτίμηση της λειτουργικής διαντίδρασης των ERβ και του NFκB κατά την καρκινογένεση στο μεταβατικό επιθήλιο της ουροδόχου κύστης με πιθανή εφαρμογή στη χημειοπρόληψη. Μεθοδολογία: Κατά την παρούσα εργασία μελετήθηκε η μεμονωμένη όσο και η συνδυαστική έκφραση των πέντε παραπάνω μορίων στο φυσιολογικό επιθήλιο και στα καρκινώματα διαφόρων Grade σε ιστικά δείγματα από 140 ασθενείς που υποβλήθηκαν σε διαγνωστική βιοψία διουρηθρική εκτομή νεοπλάσματος κύστεως η ριζική κυστεκτομή. Η μέθοδος που εφαρμόστηκε ήταν η ανοσοϊστοχημεία σε τομές παραφίνης. Αποτελέσματα: Ο παράγοντας NFκB (υπομονάδα p65) εμφάνισε μεικτή υποκυττάρια εντόπιση. Στην παρούσα ανοσοϊστοχημική μελέτη το επίπεδο της έκφρασης του NFκB στον πυρήνα των καρκινικών κυττάρων παρουσίαζε μια στατιστικά σημαντική συνολική αύξηση στα τρία επίπεδα διαφοροποίησης των καρκινωμάτων. Ο πυρηνικός υποδοχέας ERβ που εντοπίζεται στο πυρήνα των καλώς διαφοροποιημένων καρκινικών κυττάρων είναι στατιστικά σημαντικά αυξημένος σε σχέση με λιγότερο διαφοροποιημένα νεοπλασματικά κύτταρα. Στην εξέλιξη της καρκινογένεσης η COX-2 επάγεται σταθερά με διαδοχικές αυξήσεις που συνοδεύουν όλα τα στάδια της προοδευτικής αποδιαφοροποίησης των κυττάρων. Η πυρηνική έκφραση του p300 αυξάνεται σταδιακά καθώς τα καρκινώματα αποκτούν χαρακτήρες αποδιαφοροποίησης συσχέτιση στατιστικώς σημαντική. Η πυρηνική έκφραση του NCoR ελαττώνεται σταδιακά καθώς τα καρκινώματα αποκτούν χαρακτήρες αποδιαφοροποίησης συσχέτιση στατιστικώς σημαντική σύμφωνα με τα ευρήματα της παρούσας μελέτης. Συμπεράσματα: Συνολικά η χρήση αγωνιστών των ERβ και NCoR με παράλληλη αναστολή των NFκB COX-2 και NCoR θα είχε πιθανότατα ευνοϊκό αποτέλεσμα στην αναστροφή της καρκινογένεσης στην ουροδόχο κύστη. Ειδικές παράμετροι του χημειοπροληπτικού σχήματος θα ήταν ωφέλιμο να τροποποιούνται υστέρα από εξατομικευμένη αξιολόγηση του δικτύου των πέντε παραγόντων

Burned-out testicular tumor with retroperitoneal lymph node metastasis: a case report

Abstract Introduction A burned-out seminoma of the testis is an exceptionally rare clinical entity, with few reports found in the literature. Case presentation A case of burned-out tumor of the testis in a 31-year-old man is reported. The tumor presented as a retroperitoneal mass with histological characteristic of a seminoma. The testes on clinical examination were normal, and a suspicious lesion in the scrotum was only identified after ultrasound. Incision of the abdominal mass was decided, followed by orchectomy. Histological examination of the testis revealed a suspicious lesion with characteristics of spontaneous regression of germ cell tumors. Conclusion We describe one of very few cases worldwide, where spontaneous regression of a primary testicular tumor occurred after demonstration of retroperitoneal lymph node metastasis, a phenomenon known as burned-out seminoma, which is hard to recognize and incompletely characterized by physicians.</p

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research