International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus.

BACKGROUND: Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. METHODS: The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. RESULTS: In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (≥T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (≥T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. CONCLUSIONS: The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Cost Comparison of Treatment Alternatives for Pleural Effusion and Ascites from a Payer Perspective: Are There Cost Savings from Indwelling Catheters?

Background: The presence of pleural effusions and ascites in patients is often considered a marker of illness severity and a poor prognostic indicator. This study aims to compare inpatient and outpatient costs of alternative invasive treatments for ascites and pleural effusions. Methods: The retrospective single-institution study included inpatient cases treated for pleural effusion (J90 and J91) or ascites (R18) at the University Hospital Cologne (UHC) in Germany between January 01, 2020, and December 31, 2021. Costs for punctures and indwelling catheter systems (ICSs) as well as pleurodesis were analyzed in different comparator treatment pathways. Real-world data from the UHC tertiary care center were based on diagnosis-related group fees from 2020 to 2021. A simulation of outpatient expenses was carried out to compare inpatient and outpatient costs for each pathway from a payer perspective. Results: A total of 4323 cases (3396 pleural effusions and 1302 ascites) were analyzed. For ascites, inpatient implantation with home care drainage was found to be the most expensive option, with total costs of €1,918.58 per procedure, whereas outpatient puncture was the least expensive option at €60.02. For pleural effusions, the most expensive treatment pathway was pleurodesis at €8,867.84 compared with the least costly option of outpatient puncture resulting in total costs per procedure of €70.03. A break-even analysis showed that outpatient puncture remains the most inexpensive treatment option, and the ICS comprises a cost-saving potential. Longevity of several months with the use of ICSs results in both enhanced quality of life for patients and increased cost savings.

Health Economic Aspects of Platelet Concentrates: Comparing Cost and Reimbursement of Pathogen Inactivated and Conventional Platelet Concentrates in a German Comprehensive Cancer Center.

INTRODUCTION: Pathogen inactivation (PI) utilizing amotosalen and UVA light (INTERCEPT® Blood System) is a well-established method for the production of safer platelet concentrates (PCs). While many studies describe clinical and logistical benefits of PI, the implications and potential challenges from a hospital management perspective have not yet been analyzed - health economic analyses considering reimbursement of PI are lacking. The objective of this analysis was to examine the real-life inpatient treatment costs from a hospital perspective and to assess the economic impact of PI-PC versus conventional PC (CONV-PC) administration in Germany. METHODS: Real-life cost data for inpatient cancer cases from 2020 of the University Hospital Cologne were identified by operating and procedure codes. The German diagnosis-related groups, extra fees, case mix index (CMI), length of stay (LOS), and average resource consumption of PC were evaluated from a micro-management perspective. The potential economic impact of implementing PI-treated PCs was modeled retrospectively. RESULTS: In total, 951 inpatient cases were analyzed (CMI [median 4.7-9.9], LOS [median 26 days], number of cases in intensive care units [38%]). The median DRG fee was between EUR 13,800 and EUR 26,400. According to our model, the use of PI-PC compared to CONV-PC would result in savings between EUR 184 and EUR 306 per case. CONCLUSION: From a hospital management perspective, oncological cases requiring PC transfusion are associated with a high CMI (reimbursement per DRG flat fee) and moderate costs with sufficient add-on payment for PI on a case level. Investment and process costs for PI implementation can be analyzed for site-specific scenarios.

Outpatient care concept and potential inpatient cost savings associated with the administration of dalbavancin - A real-world data and retrospective cost analysis.

BACKGROUND: The treatment of acute bacterial skin and skin structure infections (ABSSSI) usually involves intravenous (i.v.) antibiotics requiring hospitalisation and increasing hospital costs. Since 2014, dalbavancin is approved for ABSSSIs treatment. However, evidence of its health economic impact on the German healthcare system is still limited. METHODS: Diagnosis-related groups (DRG) based cost analysis was used to evaluate real-world data (RWD) from a German tertiary care center. All patients treated with i.v. antibiotics in the Department of Dermatology and Venereology at the University Hospital of Cologne were included to detect potential cost savings from a payer perspective. Thus, for the inpatient care German diagnosis-related groups (G-DRG) tariffs, length of stay (LOS), main- and secondary DRG-diagnoses and for the outpatient setting 'Einheitlicher Bewertungsmaßstab' (EBM) codes were evaluated. RESULTS: This retrospective study identified 480 inpatient cases treated for ABSSSI between January 2016 until December 2020. Complete cost data were available for 433 cases and the detection of long-hospital-stay patients based on surcharges for exceeding the upper limit LOS led to 125 cases (29%) including 67 females (54%) and 58 males (46%) with an overall mean age of 63.6 years; all treated for International Classification of Diseases (ICD -10th revision) code A46 'erysipelas'. A sub-analysis focussed on DRG J64B with a total of 92 cases exceeding the upper limit LOS by a median of 3 days resulted in a median surcharge of €636 (mean value €749; SD €589; IQR €459-€785) per case. In comparison, we calculated outpatient treatment costs of approximately €55 per case. Thus, further treatment of these patients in an outpatient setting before exceeding the upper limit LOS might result in a cost-saving potential of approximately €581 per case. CONCLUSION: Dalbavancin appears a cost-efficient option to reduce inpatient treatment costs by transitioning to an outpatient setting of patients with ABSSSI potentially exceeding the upper limit LOS.

Does VO2peak Provide a Prognostic Value in Esophagectomy and Gastrectomy for Post-operative Outcomes?

BACKGROUND/AIM: Esophagectomy and gastrectomy are procedures with considerable physical burden and intense post-operative care of which the patient's physical condition seems to be a relevant predictor. The gold standard of the cardiorespiratory fitness is the peak oxygen consumption (VO2peak). This pilot study examined the prognostic value of VO2peak on post-surgery outcomes in esophageal and gastric cancer patients. PATIENTS AND METHODS: In this prospective cross-sectional study, patients scheduled for esophagectomy or gastrectomy were examined 24 h before the surgery regarding their VO2peak. The post-operative complications according to Clavien-Dindo grade IIIb/IV/V, Intensive-Care-Unit days, and overall hospital stay were documented following surgery. In a subset, body weight changes from surgery until hospital discharge and first aftercare visit were recorded. RESULTS: The functional capacity was significantly reduced in 34/35 of the included patients compared to matched norm-values (p<0.01). The only significant correlation was found between VO2peak values and body weight change from surgery to the first aftercare visit. A subgroup comparison of patients with a VO2peak <17 ml/min/kg and ≥17 ml/min/kg suggested small, non-significant differences in post-surgery outcomes and significant differences in the body weight change from surgery to hospital discharge, favoring the higher-VO2peak subgroup. CONCLUSION: The impaired functional capacity following esophagectomy or gastrectomy may strengthen the rational for exercise programs during neoadjuvant and pre-surgery phases. The prognostic value of VO2peak on post-operative outcomes remains uncertain due to noticeable descriptive differences, but no significant correlations, potentially limited by the smallsized population. Nonetheless, a correlation between VO2peak and body weight change post-surgery was observed and indicates a potential prognostic value of VO2peak.

Last Resort Antibiotics Costs and Reimbursement Analysis of Real-Life ICU Patients with Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Germany.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) cause serious infections and aggravate disease progression. Last resort antibiotics are effective against MDR-GNB and are reimbursed by flat rates based on German diagnosis-related groups (G-DRG). From a hospital management perspective, this analysis compared hospital reimbursement for last resort antibiotics with their acquisition costs to outline potential funding gaps. Retrospective analyses based on medical charts and real-life reimbursement data included patients with pneumonia due to MDR-GNB treated in intensive care units (ICU) of a German tertiary care hospital (University Hospital Cologne) between January 2017 and December 2020. Drug-associated hospital reimbursement of G-DRG was compared with drug acquisition costs based on preliminarily approved last resort antibiotics (cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-cilastatin-relebactam) according to label. Funding gaps were determined for the treatment of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and mixed infections, respectively. Most of the 31 patients were infected with Enterobacterales (n = 15; 48.4%) and P. aeruginosa (n = 13; 41.9%). Drug-associated G-DRG reimbursement varied from 44.50 EUR (mixed infection of P. aeruginosa and Enterobacterales) to 2265.27 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales). Drug acquisition costs ranged from 3284.40 EUR in ceftazidime-avibactam (minimum duration) to 15,827.01 EUR for imipenem-cilastatin-relebactam (maximum duration). Underfunding was found for all MDR-GNB, reaching from 1019.13 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales) to 14,591.24 EUR (Enterobacterales). This analysis revealed the underfunding of last resort antibiotics in German hospital treatment. Insufficient reimbursement implies less research in this field, leading to a more frequent use of inappropriate antibiotics. The cycle closes as this contributes to the development of multi-drug resistant bacteria.

Validation of 2-mm tissue microarray technology in gastric cancer. Agreement of 2-mm TMAs and full sections for Glut-1 and Hif-1 alpha.

BACKGROUND/AIM: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue. MATERIALS AND METHODS: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment. RESULTS: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides. CONCLUSION: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.

[Drug treatment of cystic fibrosis - cost patterns and savings potential for outpatient treatment]. / Medikamentöse Behandlung von Mukoviszidose - Kostenstruktur und Einsparpotenzial der ambulanten Behandlung.

BACKGROUND AND PURPOSE: Drug treatment of cystic fibrosis (CF) is associated with significant costs. To help ensure sustainable care, this study assesses the costs associated with outpatient treatment of adult CF patients in Germany. It identifies main cost drivers, evaluates the potential for cost savings from "aut idem" substitution and presents a projection of lifelong medication costs. METHODS: The analysis is based on a complete set of prescriptions for adult CF patients from the outpatient clinic of the university hospital of Frankfurt am Main during 2007 (n = 124 patients). Annual treatment costs were calculated on the basis of the "Rote Liste", while the potential for cost savings from "aut idem" drug substitution was obtained through ABDATA Pharma Data Service. RESULTS: The annual outpatient drug costs for an adult patient with CF averages € 17,219 (n = 124), which increases to € 21,782 if i.v. therapies are included. With an average life expectancy at birth of 39.7 years, total lifetime drug treatment costs amount to € 824,159 (reference year 2007, inflation rate 2.7%, 3% discount rate). "Aut idem" substitution with cheaper drugs could reduce pharmaceutical expenditures by 4.1%. CONCLUSION: Our results confirm the costly nature of drug treatment for CF patients, both on an annual and in particular on a lifelong basis. At the same time, the potential for cost savings through "aut idem" substitution with cheaper drugs remains limited. The added transparency around a small set of costdriving drugs, which is offered in this study, represents a solid contribution to assess treatment choices and financing options to help secure adequate yet sustainable care for CF patients.