Explore the vast range of titles available.

Background Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination. Methods EGFR overexpression (EGFR over ) was tracked in 1039 primary tumours, circulating tumour cells from 39 d’Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices. Results EGFR over was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFR over correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFR over was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness. Conclusions EGFR over is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.

Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative “Achilles heel” of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.

Background/Objectives: Since 2020, Germany has replaced its annual cytological screening for cervical cancer in women aged 35 and older with a combination screening program. This updated protocol, conducted every three years, includes both a cervical Pap smear and an HPV (human papillomavirus) test. In addition, the 2020 update of the German Cervical Cancer Screening Program mandates a more timely follow-up for certain abnormal findings compared to the previous approach. Methods: Results of cytologic, colposcopic, and histologic examinations between 2018 and 2021 were retrospectively retrieved from the electronic patient records of the Institute of Pathology Saarbrücken Rastpfuhl in order to present relevant findings within the years 2018–2019 and 2020–2021. The present study included all women who received appropriate follow-up based on the corresponding underlying screening modality. Results: Our reporting considered data from 30,715 women in 2018/19 (prior screening modality group) and 25,924 women in 2020/21 (updated screening modality group). In 2018/19, a total of 93 histological examinations were performed, compared to 237 in 2020/21. In 2018/19, 52 cases of CIN III and 12 cases of CIN II were identified, while in 2020/21, 78 cases of CIN III and 31 cases of CIN II were detected. In contrast, while women with negative cytological findings in 2018/19 were typically not referred for further colposcopic or histological evaluation, the updated program enabled earlier detection and treatment of cases with diagnosed high-grade dysplasia based solely on a positive HPV test. Notably, 31 women who were diagnosed at an earlier stage based solely on a positive HPV test initially presented with a cytological Pap I result (negative for intraepithelial lesion or malignancy; NILM). Conclusions: Additional HPV co-testing within the updated German cervical cancer screening program resulted not only in high rates of high-grade dysplasia detection but also a rise in the number of colposcopic procedures. While negative follow-up HPV findings regularly showed remission of the original finding, incidence of high-grade dysplasia was usually linked to a positive HPV test.

Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

See PDF.] a An estimated 22-mm colorectal lesion across a proximal colon fold. b After submucosal injection, pseudo-depressed areas emerged, and the lesion was classified as an LSL-NG/PD, Paris IIa+IIc. c, d Distorted vessel structure and amorphous surface pattern were appreciated on linked colour (LCI) and blue laser imaging (BLI), respectively, raising concern of potentially advanced neoplasia (tentatively classified as analogous to a NICE type 3 lesion). e Ex vivo demonstration of the additional working channel (AWC) device (Ovesco Endoscopy, Tübingen, Germany) attached to the scope’s shaft (valve) (c) and tip (AWC) (d). [...]the tightly snared lesion is then resected en bloc by routine electrocautery settings as in standard EMR procedures, e.g., EndoCutQ, effect 2, duration 4, interval 3 (Fig. 2c). See PDF.] a An anchor through the AWC lifts up the lesion into a 25-mm snare in a modified “grasp-and-snare” fashion. b Coordinated mobilization and pushing back using the anchor prior to full and tight snare closure to avoid muscularis propria entrapment/perforation (“push-back” technique), followed by electrosurgical resection using standard EMR settings (c). d Evaluation of the resection site excluding deep mural injury/perforation.

Beyond the previously detected small sessile lesion, the full lesion extent was, at the time, visualized after ineffective submucosal indigo carmine injection related to exuberant postsurgical fibrosis and acetic acid spraying, albeit as yet with low-level evidence, highlighting the serrated lesion and its borders [5, 6]. Notwithstanding that recent data indicate feasibility of simple EMR in appendiceal lesions involving <50 % of the circumference with an identifiable proximal extension, the presented clinical report is unique in terms of status post-appendectomy as well as a carpet-like, utterly flat extension of an estimated 15-mm serrated lesion occupying the whole appendix rest [7]. See PDF.] a A “cecal mucus sign” was identified during screening colonoscopy. b, cAfter extensive washings, no clear-cut mucosal abnormality was identified by white light and image-enhanced endoscopy – note argon plasma coagulation (APC) sites due to cecal angiodysplasias. d Only after forceps manipulation, a submerged lesion was unmasked, pathologically confirmed as a sessile serrated adenoma/polyp (SSA/P) without dysplasia. e Beyond previously detected small sessile parts, the full lesion extent was visualized after acetic acid spraying and underwater endoscopy, revealing a carpet-like involvement with a diffusely velvety appearance. f Endoscopic piecemeal resection was achieved by cold snare resection and cap-assisted aspiration mucosectomy.

Over the last century, the narrative of cervical cancer history has become intricately tied to virus research, particularly the human papillomavirus (HPV) since the 1970s. The unequivocal proof of HPV’s causal role in cervical cancer has placed its detection at the heart of early screening programs across numerous countries. From a historical perspective, sexually transmitted genital warts have been already documented in ancient Latin literature; the remarkable symptoms and clinical descriptions of progressed cervical cancer can be traced back to Hippocrates and classical Greece. However, in the new era of medicine, it was not until the diagnostic–pathological accomplishments of Aurel Babeş and George Nicolas Papanicolaou, as well as the surgical accomplishments of Ernst Wertheim and Joe Vincent Meigs, that the prognosis and prevention of cervical carcinoma were significantly improved. Future developments will likely include extended primary prevention efforts consisting of better global access to vaccination programs as well as adapted methods for screening for precursor lesions, like the use of self-sampling HPV-tests. Furthermore, they may also advantageously involve additional novel diagnostic methods that could allow for both an unbiased approach to tissue diagnostics and the use of artificial-intelligence-based tools to support decision making.

Background Histopathological evaluation of prostatectomy specimens is crucial to decision-making and prediction of patient outcomes in prostate cancer (PCa). Topographical information regarding PCa extension and positive surgical margins (PSM) is essential for clinical routines, quality assessment, and research. However, local hospital information systems (HIS) often do not support the documentation of such information. Therefore, we investigated the feasibility of integrating a cMDX-based pathology report including topographical information into the clinical routine with the aims of obtaining data, performing analysis and generating heat maps in a timely manner, while avoiding data redundancy. Methods We analyzed the workflow of the histopathological evaluation documentation process. We then developed a concept for a pathology report based on a cMDX data model facilitating the topographical documentation of PCa and PSM; the cMDX SSIS is implemented within the HIS of University Hospital Muenster. We then generated a heat map of PCa extension and PSM using the data. Data quality was assessed by measuring the data completeness of reports for all cases, as well as the source-to-database error. We also conducted a prospective study to compare our proposed method with recent retrospective and paper-based studies according to the time required for data analysis. Results We identified 30 input fields that were applied to the cMDX-based data model and the electronic report was integrated into the clinical workflow. Between 2010 and 2011, a total of 259 reports were generated with 100% data completeness and a source-to-database error of 10.3 per 10,000 fields. These reports were directly reused for data analysis, and a heat map based on the data was generated. PCa was mostly localized in the peripheral zone of the prostate. The mean relative tumor volume was 16.6%. The most PSM were localized in the apical region of the prostate. In the retrospective study, 1623 paper-based reports were transferred to cMDX reports; this process took 15 ± 2 minutes per report. In a paper-based study, the analysis data preparation required 45 ± 5 minutes per report. Conclusions cMDX SSIS can be integrated into the local HIS and provides clinical routine data and timely heat maps for quality assessment and research purposes.

Background The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. Methods The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. Results The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. \"cMDX\" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. Conclusions cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.

Endothelin (ET)-1 and its receptors ET-A and ET-B, referred to commonly as the endothelin axis, have been identified in various human cancers, especially gynecologic tumors, such as breast cancer or ovarian cancer, but also including urologic tumor entities. They play a key role in tumor growth and progression by influencing critical cancer pathways, such as apoptosis, angiogenesis and proliferation. In prostate cancer, overexpression of the ET-A receptor increases with tumor progression, and clinical trials with selective ET-A receptor antagonists, such as atrasentan (ABT-627), have shown promising early results. In preclinical models of bladder cancer, overexpression of the ET axis has been demonstrated and ET-targeting agents are under investigation. This paper reviews the role of the ET axis in human cancers and focuses on preclinical and clinical studies in urologic tumor entities to further define the role of ET-targeting agents as targeted molecular therapy.