Background: Even though numerous novel lymph node (LN) classification schemes exist, an extensive comparison of their performance in patients with resected pancreatic ductal adenocarcinoma (PDAC) has not yet been performed. Method: We investigated the prognostic performance and discriminative ability of 25 different LN ratio (LNR) and 27 log odds of metastatic LN (LODDS) classifications by means of Cox regression and C-statistic in 319 patients with resected PDAC. Regression models were adjusted for age, sex, T category, grading, localization, presence of metastatic disease, positivity of resection margins, and neoadjuvant therapy. Results: Both LNR or LODDS as continuous variables were associated with advanced tumor stage, distant metastasis, positive resection margins, and PDAC of the head or corpus. Two distinct LN classifications, one LODDS and one LNR, were found to be superior to the N category in the complete patient collective. However, only the LODDS classification exhibited statistically significant, gradually increasing HRs of their subcategories and at the same time significantly higher discriminative potential in the subgroups of patients with PDAC of the head or corpus and in patients with tumor free resection margins or M0 status, respectively. On this basis, we built a clinically helpful nomogram to estimate the prognosis of patients after radically resected PDAC. Conclusion: One LNR and one LODDS classification scheme were found to out-perform the N category in terms of both prognostic performance and discriminative ability, in distinct patient subgroups, with reference to OS in patients with resected PDAC.

Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients with Stage III radically resected CRC.

Background Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations. Methods Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models. Results A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p < 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73–1.86, p < 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91–2.37, p < 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76–1.95, p < 0.001). Conclusions The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.

Background Gastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor site, stage and differentiation. However, systematic data on the epidemiology of GI-NET, especially in terms of geographic distributions are missing. Methods We used the Oncology Dynamics database (IQVIA) to identify a total of 1354 patients with GI-NET from four European countries (Germany, France, Spain, UK) and compared them with regard to major patient and tumor related characteristics including patients’ age, sex, tumor stage, tumor grading and differentiation. Results Out of the analyzed 1354 NET patients, 535 were found in the UK (39.5%), 289 in Germany (21.3%), 283 in Spain (20.9%) and 247 in France (18.2%). More patients were male than female (53.8% vs. 46.2%) with no significant differences between the analyzed countries. In contrast, the age distribution varied between the different countries, with the highest number of patients identified in the age groups of 61–70 years (31.0%) and 71–80 years (30.7%). The vast majority of patients showed a tumor origin in the small intestine, in German patients NET of the large intestine were slightly overrepresented and NET of the stomach underrepresented compared to all other countries. More than 80% of patients had stage IV disease at the time of diagnosis. Regarding tumor histology, most tumors showed a G2 tumor; interestingly, a G3 grading was found in 40.9% of patients in Germany (Ki-67 > 20%). Conclusion The distribution of important patient- and tumor-specific characteristics of neuroendocrine tumors shows regional differences in four major European countries. These data may help to better understand the specific epidemiology of GI-NET in Europe.

Background: Cancer represents one of the leading causes of death worldwide. Besides genetic risk factors and non-communicable diseases, chronic infections including Epstein–Barr virus (EBV) infection have been identified as promotors of cancer. In the present manuscript, we evaluated the association between infectious mononucleosis, the clinical manifestation of EBV infection, and cancer development in a real-word cohort of outpatients in Germany. Methods: We used the Disease Analyzer database (IQVIA) and matched a total of 12,095 patients with infectious mononucleosis to a cohort of individuals without infectious mononucleosis based on age, sex, index year, and annual patient consultation frequency between 2000 and 2018. Results: Patients diagnosed with infectious mononucleosis had a cancer incidence of 5.3 cases per 1000 person years versus 4.4 cases per 1000 person years for patients without infectious mononucleosis. In multivariable regression models, infectious mononucleosis showed a trend towards a higher incidence of cancer in general in the age group > 50 years (incidence rate ratio (IRR): 1.32; 95% CI: 1.04–1.67) and among men (IRR: 1.36; 95% CI: 1.07–1.72). Infectious mononucleosis was significantly associated with an increased incidence of tumors of the hematopoietic and lymphoid tissues (IRR: 1.75; 95% CI: 1.22–2.50) and showed a strong trend towards an association with prostate cancer (IRR: 3.09; 95% CI: 1.23–7.76). Conclusion: Infectious mononucleosis is associated with an increased incidence of certain cancer types. The present data from a large real-world cohort support the evidence on a role of EBV in the development of different malignancies and could trigger research efforts to further elucidate its precise involvement in the carcinogenic process.

(1) Background: Transarterial chemoembolization (TACE) is a minimally invasive procedure, characterized by the selective occlusion of tumor-feeding hepatic arteries, via injection of an embolizing agent and an anticancer drug. It represents a standard of care for intermediate-stage hepatocellular carcinoma (HCC), and it is also increasingly performed in cholangiocarcinoma (CCA), as well as in liver metastases. Apart from the original method, based on intra-arterial infusion of a liquid drug followed by embolization, newer particle-based TACE procedures have been introduced recently. As yet, comprehensive data on current trends of TACE, as well as its in-hospital mortality in Germany, which could help to further improve outcome following TACE, are missing. (2) Methods: Based on standardized hospital discharge data, provided by the German Federal Statistical Office from 2010 to 2019, we aimed at systematically evaluating current clinical developments and in-hospital mortality related to TACE in Germany. (3) Results: A total of 49,595 individual cases undergoing TACE were identified within the observation period. The overall in-hospital mortality was 1.00% and significantly higher in females compared to males (1.12 vs. 0.93%; p < 0.001). We identified several post-interventional complications, such as liver failure (51.49%), sepsis (33.87%), renal failure (23.9%), and liver abscess (15.87%), which were associated with a significantly increased in-hospital mortality. Moreover, in-hospital mortality significantly differed between the underlying indications for TACE (HCC: 0.83%, liver metastases: 1.22%, and CCA: 1.40%), as well as between different embolization agents (liquid embolization: 0.80%, loaded microspheres: 0.92%, spherical particles: 1.54%, and non-spherical particles: 2.84%), for which we observed large geographic differences in their frequency of use. Finally, in-hospital mortality was significantly increased in centers with a low annual TACE case volume (<15 TACE/year: 2.08% vs. >275 TACE/year: 0.45%). (4) Conclusion: Our data provide a systematic overview of indications and embolization methods for TACE in Germany. We identified a variety of factors, such as post-interventional complications, the embolization method used, and the hospitals’ annual case volume, which are associated with an increased in-hospital mortality following TACE. These data might help to further reduce the mortality of this routinely performed local-ablative procedure in the future.

Purpose Gastroenteropancreatic neuroendocrine neosplasms (GEP-NEN) are biologically heterogenous tumors with an increasing incidence over the past decades. Although efforts have been made in the treatment of these tumors, survival rates in metastasized tumor stages remain frustrating. Thus, there is an urgent need to identify novel targets as alternative treatment options. In this regard, the inhibitor of apoptosis protein (IAP) family member survivin could be such an attractive target. Therefore, aim of our meta-analysis was to assess the role of survivin as a biomarker and predictor in GEP-NEN. Methods Medline, Web of Science and Scopus were screened for studies that fulfilled our selection criteria. Quality assessement of the studies was based on design, methodology, generalizability and results analysis. Meta-analyses were conducted using a random-effects model and effect size measures were expressed as pooled Hazard Ratio (HR) or Odds Ratio (OR) with 95% Confidence Interval (CI). Results Six eligible studies with 649 patients (range 77–132) assessed survivin expression in GEP-NEN by immunohistochemistry. High expression levels of nuclear survivin in GEP-NEN correlated with a shorter overall survival (HR 3.10; 95% CI 2.15–4.47; p < 0.0001). In contrast to cytoplasmic survivin (OR 1.24; CI 0.59–2.57; p = 0.57), nuclear survivin was also associated (OR 15.23; CI 3.61–64.23; p = 0.0002) with G3/poorly differentiated GEP-NEN. Conclusion Nuclear Survivin is highly expressed in more aggressive G3 GEP-NEN and correlates with a poor outcome. Survivin is therefore an interesting molecule for a targeted therapy, especially for patients with highly proliferative G3 GEP-NENs.

Background: Palliative care comprises multiprofessional, integrated, person-centered healthcare services for patients and their families facing problems related to progressive or advanced diseases and limited life expectancy. Although non-oncology patients’ needs are similar to those of tumor patients, they are often underestimated. The purpose of our study was to investigate the actual utilization of palliative care services in Germany, especially in the outpatient setting. Methods: Using the IQVIA Disease Analyzer database, a total of 14,792 outpatients from 805 primary care practices in Germany with documented palliative care and related diagnosis between 2018 and 2021 were analyzed. Proportions of different diagnoses among patients receiving outpatient palliative care were stratified by gender and different age groups. Results: The most common underlying diagnosis for outpatient palliative care was cancer (55%), followed by heart failure (16%) and dementia (8%), with age- and sex-specific differences found in the proportion of diagnoses for utilization. While the relative proportions of cancers decreased with age (87% in the 18- to 50-year-old age group versus 37% in the 80-plus age group), the proportion of palliative care related to heart failure increased in the older population (2% in the 18- to 50-year-old age group versus 25% in the 80-plus age group). Conclusions: This study provides an overview of the situation of outpatient palliative care in Germany and shows age- and gender-specific trends regarding the underlying medical diagnoses. Based on these data, palliative care should be adapted to current demographic developments.