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Compared to other malignancies, there is a lack of easy-to-evaluate biomarkers for gastric cancer, which is associated with an adverse clinical outcome in many cases. Here, we present Stroma AReactive Invasion Front Areas (SARIFA) as a new histological prognostic marker. We defined SARIFA as the direct contact between a cluster of tumor glands/cells comprising at least five tumor cells and inconspicuous surrounding adipose tissue at the invasion front. A total of 480 adenocarcinomas of the stomach and the gastroesophageal junction from two different collections were classified according to SARIFA. To understand the potential underlying mechanisms, a transcriptome analysis was conducted using digital spatial profiling (DSP). It was found that 20% of the tumors were SARIFA-positive. Kappa values between the three pathologists were good in both collections: 0.74 and 0.78. Patients who presented SARIFA-positive tumors had a significantly lower overall survival in Collections A (median: 20.0 versus 44.0 months; p = 0.014, n = 160) and B (median: 15.0 versus 41.0 months; p < 0.0001, n = 320). SARIFA positivity emerged as a negative independent prognostic factor for overall survival (HR 1.638, 95% CI 1.153-2.326, p = 0.006). Using DSP, the most upregulated genes in SARIFA-positive cases were those associated with triglyceride catabolism and endogenous sterols. COL15A1, FABP2, and FABP4 were differentially expressed in positive cases. At the protein level, the expression of proteins related to lipid metabolism was confirmed. SARIFA combines low inter-observer variability, minimal effort, and high prognostic relevance, and is therefore an extremely promising biomarker related to tumor-promoting adipocytes in gastric cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p &lt, 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (&lt, 1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

Introduction: In the last century, there have been major changes within the population structure in Germany. The aim of this study was to determine the impact of a changing population structure on identification of familial prostate cancer (PCa), and to investigate how many and which types of other cancers have occurred in patients and their first-degree relatives. Materials and Methods: A total of 19,540 patients were evaluated in a prospectively collected PCa family database and divided into four birth cohorts: 1925–1934 (cohort A), 1935–1944 (cohort B), 1945–1954 (cohort C), and 1955–1964 (cohort D). Other primary cancers and cancers of first-degree relatives were evaluated. Results: The percentage of PCa patients with ≥2 sons declined (A: 28.9% to D: 21.6%). The percentage of patients whose fathers lived for ≥65 years increased (B: 64.2% to D: 73.0%). Malignancies of the skin, the urinary tract, and the lymphoid/hematopoietic tissue were more common in patients with a positive first-degree PCa family history and their first-degree relatives. Additionally, first-degree relatives reported more often neoplasms of respiratory/intrathoracic organs and the female breast. Conclusions: A small family size, an early deceased father, and a high number of sporadic cases complicate the identification of familial PCa patients. Thus, a detailed family history should also include unaffected first-degree relatives to avoid any misclassification. Findings of other primary cancers in patients and their relatives warrant further investigation.

Das Internet bietet zahlreiche Informationen uber das Prostatakarzinom (PCa). Inwieweit PCa-Langzeituberlebende das Internet nutzen, den gefundenen Informationen vertrauen und von welchen Parametern dies abhangig ist, wurde in vorliegender Studie untersucht. Auf Basis der nationalen Datenbank „Familiares Prostatakarzinom“ wurden Langzeituberlebende 2017 hinsichtlich ihrer Internetnutzung befragt und die Assoziation zu soziodemographischen (Befragungsalter, Kinder, Partnerschaft, Schulbildung) und krankheitsbezogenen Parametern (Zeit seit Diagnose, PCa-Familienanamnese, Progress) mittels multipler logistischer Regression analysiert. In die Analyse gingen 4636 PCa-Langzeituberlebende (Alter: M = 76,9 ± 6,6 Jahre) mit einem durchschnittlichen Follow-up von 14,0 Jahren ein. 62,1 % der PCa-Langzeituberlebenden nutzten das Internet. Unter den Nichtnutzern hatten 23,5 % starke Bedenken, bei den Nutzern nur 2,8 %. 47,2 % der Nutzer suchten nach PCa-Informationen, davon gaben 18,0 % Schwierigkeiten an. Mehr als die Halfte fand die Informationen zum PCa unpassend. Niedrigeres Alter, kurzere Zeit seit Diagnose, Progress und haufigere Internetnutzung waren mit PCa-bezogener Informationssuche assoziiert. Nur ein Drittel vertraute den Informationen voll. Dieses Vertrauen war mit einem hohen Alter, hoherer Schulbildung und haufiger Informationssuche assoziiert. Viele gaben an, v. a. ihrem Urologen zu vertrauen. Zwei Drittel der PCa-Langzeituberlebenden nutzt das Internet. Bei der PCa-Informationssuche bestehen Schwierigkeiten, passende und vertrauenswurdige Informationen zu finden. Urologen sollten daher mit Internetangeboten vertraut sein, um Patienten beraten und internetbezogene Informationen empfehlen zu konnen.

In symptomatic patients with acute Coronavirus disease 2019 (COVID‐19), lymphocytopenia is one of the most prominent laboratory findings. However, to date age and gender have not been considered in assessment of COVID‐19‐related cell count alterations. In this study, the impact of COVID‐19 as well as age and gender on a large variety of lymphocyte subsets was analyzed in 33 COVID‐19 patients and compared with cell counts in 50 healthy humans. We confirm that cell counts of total lymphocytes, B, NK, cytotoxic and helper T cells are reduced in patients with severe COVID‐19, and this tendency was observed in patients with moderate COVID‐19. Decreased cell counts were also found in all subsets of these cell types, except for CD4+ and CD8+ effector memory RA+ (EMRA) and terminal effector CD8+ cells. In multivariate analysis however, we show that in addition to COVID‐19, there is an age‐dependent reduction of total, central memory (CM), and early CD8+ cell subsets, as well as naïve, CM, and regulatory CD4+ cell subsets. Remarkably, reduced naïve CD8+ cell counts could be attributed to age alone, and not to COVID‐19. By contrast, decreases in other subsets could be largely attributed to COVID‐19, and only partly to age. In addition to COVID‐19, male gender was a major factor influencing lower counts of CD3+ and CD4+ lymphocyte numbers. Our study confirms that cell counts of lymphocytes and their subsets are reduced in patients with COVID‐19, but that age and gender must be considered when interpreting the altered cell counts.

In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups for the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. We enrolled 291 colon cancer patients with pT3 and pT4 adenocarcinomas and converted one cytokeratin-stained representative tumor section per case into a binary image. Image augmentation and dropout layers were incorporated to avoid overfitting. In a validation collective (n = 128), BIg-CoMet was able to discriminate well between patients with and without metastasis (AUC: 0.842, 95% CI: 0.774–0.911). Further, the Kaplan–Meier curves of the metastasis-free survival showed a highly significant worse clinical course for the high-risk group (log-rank test: p &lt, 0.001), and we demonstrated superiority over other established risk factors. A multivariable Cox regression analysis adjusted for confounders supported the use of risk groups as a prognostic factor for the occurrence of metastasis (hazard ratio (HR): 5.4, 95% CI: 2.5–11.7, p &lt, 0.001). BIg-CoMet achieved good performance for both UICC subgroups, especially for UICC III (n = 53), with a positive predictive value of 80%. Our study demonstrates the ability to stratify colon cancer patients via a semi-guided process on images that primarily reflect tumor architecture.

Background COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. Methods During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. Results Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. Conclusions The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.

Objectives Long‐term prospective studies on procedure‐related complications after parotid surgery for benign neoplasms (BNs) are scarce. This is the first prospective study on the use of extracapsular dissection (ECD) for BNs, and it aimed to examine the incidence of postoperative complications after parotid surgery for BN. Methods We collected data obtained in a prospective study of parotidectomy for BN at a university hospital and analyzed the transient and long‐term complications. Results The incidence rates of transient facial palsy immediately and 18 months after surgery were 15.0% and 3.7%, respectively. The rates of immediate postoperative facial palsy in patients who underwent ECD, partial superficial, superficial, and total parotidectomy were 5.8%, 29.3%, 20.0%, and 44.1%, respectively. Significant risk factors for facial palsy included multiple and larger lesions as well as surgery duration and extension. Conclusions Postoperative facial palsy remains a common complication after parotidectomy for BN and is associated with the extent of parotidectomy, presence of multiple neoplasms, and operative duration. The results of this study showed that ECD could be a safe technique for avoiding facial palsy. Level of Evidence: 2.

Regular self-examination can facilitate early detection of testicular cancer and malignancies of the breast and may ensure a curative treatment. In this analysis we explored the tendencies of medical students to perform self-examination and associated factors.As part of their urology rotation, medical students of the Technical University of Munich were surveyed via questionnaires regarding their health and sexual behavior. In all, 98.8% of the students participated and data from 473 of 477 students were included in this analysis. Data were analyzed using univariate and multivariate regression analysis.In all, 64.2% (n = 177) of the male students and 72.3% (n = 296) of the female students performed regular self-examination of the testis and breast, respectively. Students who did not communicate with their partners or friends about their sex lives were less likely to preform regular self-examination (p 0.05). Male students without sexual intercourse in the 4 weeks prior to the survey and female students who did not masturbate in the 4 weeks prior to the survey were also less likely to preform regular self-examination (p 0.05).The rate of regular self-examination is high in medical students compared to previous studies on young adults and non-medical students. This shows that knowledge about the significance of testicular cancer and breast cancer are fundamental for promoting self-examination in teenagers and young adults. A distressed sex life might hinder young adults in preforming regular self-examination. Therefore, improved education about the significance of testicular cancer and routine urological consultations for male teenagers and young men are ways to promote testicular self-examination within this age group.HINTERGRUND: Durch eine regelmäßige Selbstuntersuchung kann ein Malignom der Hoden oder Brust gegebenenfalls frühzeitig erkannt und kurativ behandelt werden. Ziel dieser Arbeit war es, das Selbstuntersuchungsverhalten von Medizinstudierenden zu untersuchen und Faktoren, die eine regelmäßige Selbstuntersuchung beeinflussen, zu identifizieren.Medizinstudierende wurden mittels Fragebogen bezüglich ihres Gesundheits- und Sexualverhaltens befragt. 98,8 % der Studierenden nahmen teil (n = 473). Die erhobenen Daten wurden mittels univariater und multivariater logistischer Regression analysiert.Es gaben 64,2 % der männlichen Studierenden (n = 177) an, regelmäßig ihre Hoden zu untersuchen und 72,2 % der weiblichen Studierenden (n = 296) gaben an, regelmäßig ihre Brust abzutasten. Studierende, die nicht mit ihrer/ihrem PartnerIn bzw. mit ihren FreundInnen über ihre Sexualität sprechen, führten seltener eine Selbstuntersuchung durch (p 0,05). Männliche Studierende, die in den letzten 4 Wochen vor Befragung keinen Geschlechtsverkehr hatten und weibliche Studierende, die im gleichen Zeitraum nicht masturbierten, führten seltener eine Selbstuntersuchung durch (p 0,05).Der Anteil an Medizinstudierenden, der eine regelmäßige Selbstuntersuchung durchführt, ist im Vergleich zu weniger medizinisch gebildeten jungen Erwachsenen hoch. Wissen über die Relevanz von Hoden- bzw. Brustkrebs scheint grundlegend für eine regelmäßige Selbstuntersuchung zu sein. Ein belastetes Sexualleben schränkt solch ein Gesundheitsverhalten möglicherweise ein. Eine Verbesserung der Aufklärung über Hodenkrebs und die urologische Anbindung von Jungen/junger Männer bieten daher die Möglichkeit, die Bereitschaft zur Selbstuntersuchung innerhalb dieser Altersgruppe zu steigern.

Purpose To assess whether a first-degree family history or a fatal family history of prostate cancer (PCa) are associated with postoperative upgrading and upstaging among men with low risk and favourable intermediate-risk (FIR) PCa and to provide guidance on clinical decision making for active surveillance (AS) in this patient population. Methods Participants in the German Familial Prostate Cancer database diagnosed from 1994 to 2019 with (1) low risk (clinical T1c–T2a, biopsy Gleason Grade Group (GGG) 1, PSA Results Among 4091 men who underwent RP, mean age at surgery was 64.4 (SD 6.7) years, 24.7% reported a family history, and 3.4% a fatal family history. Neither family history nor fatal family history were associated with upgrading or upstaging at low risk, Gleason 6 FIR, and Gleason 3 + 4 FIR PCa patients. Conclusion Results from the current study indicated no detrimental effect of family history on postoperative upgrading or upstaging. Therefore, a positive family history or fatal family history of PCa in FIR PCa patients should not be a reason to refrain from AS in men otherwise suitable.

Purpose The safety of active surveillance (AS) in favorable intermediate-risk (FIR) prostate cancer (PCa) remains uncertain. To provide guidance on clinical decision-making, we examined long-term and pathological outcomes of low-risk and intermediate-risk PCa patients after radical prostatectomy (RP). Methods The study involved 5693 patients diagnosed between 1994 and 2019 with low-risk, FIR, and unfavorable intermediate-risk (UIR) PCa (stratification according to the AUA guidelines) who underwent RP. Pathological outcomes were compared, and Kaplan–Meier analysis determined biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) at 5, 10, 15, and 20 years. Multiple Cox regression was used to simultaneously control for relevant confounders. Results Those at FIR had higher rates of upgrading and upstaging (12.8% vs. 7.2%, p p p p > 0.001) compared to patients at low risk. The 20-year BRFS was 69%, 65%, and 44% and the 20-year CSS was 98%, 95%, and 89% in low-risk, FIR, and UIR patients. On multiple Cox regression, FIR was not associated with a worse BRFS (HR 1.07, CI 0.87–1.32), UIR was associated with a worse BRFS (HR 1.49, CI 1.20–1.85). Conclusion Patients at FIR had only slightly worse pathological and long-term outcomes compared to patients at low risk, whereas the difference compared to patients at UIR was large. This emphasizes AS in these patients as a possible treatment strategy in well-counseled patients.

Background Although fear of cancer recurrence (FCR) or disease progression is among the most endorsed unmet needs and concerns of cancer survivors, research on the course of FCR in long-term survivors is scarce. The objective of this study was to assess longitudinally the prevalence and predictors of FCR in long-term prostate cancer (PCa) survivors. Methods In all, 2417 survivors from the multicenter German Familial Prostate Cancer Database completed the Fear of Progression Questionnaire-Short Form on average 7 years (T1 in 2010) after radical prostatectomy and at follow-up 9 years later (T2 in 2019). Hierarchical multivariable logistic regression was used to assess predictors of FCR at follow-up. Results The mean age at the initial assessment was 69.5 years (standard deviation, 5.9 years); 6.5% and 8.4% of patients reported clinical FCR at the initial assessment (T1) and at the follow-up (T2), respectively. In a multivariable analysis controlling for concurrent associations, longitudinal predictors of FCR 9 years later included a lower level of education (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.33-8.33), years since radical prostatectomy (OR, 1.10; 95% CI, 1.03-1.18), biochemical recurrence (OR, 1.67; 95% CI, 1.02-2.72), no current adjuvant therapy (OR, 2.38; 95% CI, 1.19-4.76), FCR (OR, 10.75; 95% CI, 6.18-18.72), and anxiety (OR, 1.35; 95% CI, 1.06-1.72). Conclusions FCR remains a burden to certain PCa survivors even many years after their diagnosis and treatment. Health care professionals should monitor for FCR and identify patients at risk to provide appropriate psychosocial care because FCR is leading to limitations in quality of life and psychological well-being.

INTRODUCTION AND OBJECTIVE:Factors such as prostatitis or benign prostate hyperplasia are known to increase PSA levels. Previous studies have found higher PSA levels after ejaculation, however, kno...