Florian Gebauer

Background: The optimal interventional approach for necrotizing pancreatitis remains debated. We performed a systematic review with network meta‐analysis and proportional meta‐analysis to compare endoscopic trans‐gastric necrosectomy (EN), minimally invasive surgical necrosectomy (MIN), and open necrosectomy (ON). Methods: Databases were searched from inception through March 2026. Eligible studies included randomized and observational comparative studies enrolling adults with necrotizing pancreatitis requiring necrosectomy and comparing ON, MIN, and/or EN. Nine binary outcomes were assessed in a frequentist random‐effects network meta‐analysis. Separate proportional meta‐analysis of single‐arm studies pooled mortality, clinical success, complications, and need for additional surgery. Risk of bias was assessed using RoB 2 and ROBINS‐I, and confidence in network estimates was assessed using CINeMA. Results: Thirty‐three studies were included. Nine comparative studies were included in the network meta‐analysis, and 24 single‐arm studies were analyzed separately. EN was associated with lower mortality, fewer complications, less new‐onset multiple organ failure, less exocrine insufficiency, fewer new ICU admissions, and better overall treatment ranking than ON. EN also outperformed MIN for complications and new‐onset multiple organ failure, whereas MIN was superior to ON for multiple organ failure, exocrine insufficiency, incisional hernia, and ICU admission. Bleeding, re‐intervention, and new‐onset diabetes did not differ significantly across techniques. In single‐arm pooling, EN and MIN showed comparable mortality, clinical success, complications, and need for additional surgery. Conclusions: Endoscopic necrosectomy appears to offer the most favorable overall profile for necrotizing pancreatitis, whereas minimally invasive surgical approaches also improve several outcomes compared with open necrosectomy. Open surgery should likely remain reserved for selected rescue situations.

Background: Obesity poses technical challenges in adrenalectomy. Robotic adrenalectomy (RA) offers advantages over laparoscopic adrenalectomy (LA), but evidence in obese patients remains limited. Methods: A meta‐analysis of comparative studies through 2025 assessed perioperative outcomes of RA versus LA, with subgroup analyses by body habitus (obese vs. non‐obese) and surgical approach (lateral transabdominal [LT] vs. posterior retroperitoneal [PR]). Primary outcomes included operative time (OT), blood loss (EBL), hospital stay (LOHS), complications, conversion, and mortality. Study quality was evaluated using the Newcastle–Ottawa Scale, and certainty was assessed using the GRADE approach. Results: Eight studies (1107 patients) were included. RA was associated with reduced EBL ( p < 0.001) and shorter LOHS ( p < 0.001), with no other significant differences. Subgroup analysis showed shorter LOHS in non‐obese LA patients ( p = 0.03). PR showed a shorter LOHS ( p = 0.001) compared with LT. Conclusions: RA provides perioperative benefits, particularly reduced blood loss and shorter hospital stay, without compromising safety.

Das Pankreaskarzinom zählt weltweit zu den tödlichsten Krebsarten. Aufgrund der schlechten Prognose liegt die Mortalität nahezu auf dem Niveau der Inzidenz, mit einer 5-Jahres-Überlebensrate von nur 11%. Seit 2023 steht mit NALIRIFOX eine neue Erstlinientherapie zur Verfügung, die gegenüber GEM-NABP einen Überlebensvorteil zeigt und laut aktueller Netzwerk-Metaanalyse ein günstigeres Nebenwirkungsprofil als das etablierte FOLFIRINOX aufweist. Im Zuge gesundheitspolitischer Bestrebungen zur Verlagerung stationärer Leistungen in den ambulanten Bereich – zunehmend auch in der Onkologie – gewinnen insbesondere jene Therapien an Bedeutung, deren Toxizitätsprofil eine ambulante Durchführung ermöglicht. Auf Grundlage dreier typisierter Versorgungsszenarien (ambulant, Hospitalisierung im Verlauf, primär stationär) wurden die ökonomischen Effekte der geringeren Toxizität modellhaft analysiert. Für eine hypothetische Kohorte von 100 Patient:innen ergeben sich Einsparpotenziale von 22.076,17 € im ambulanten Setting, 24.578,69 € bei hospitalisierungsbedingten Komplikationen und über 98.000 € im stationären Bereich infolge verlängerter Verweildauer. NALIRIFOX kann somit nicht nur wirtschaftliche Vorteile bieten, sondern auch die Lebensqualität durch reduzierte Nebenwirkungen verbessern. Die Ergebnisse unterstreichen die Relevanz eines gezielten Nebenwirkungsmanagements sowie den Bedarf an validierenden Untersuchungen mit Routinedaten.

Purpose: Pain and reduced quality of life (QoL) are major subjects of interest after surgery for hemorrhoids. The aim of this study was to find predictive parameters for postoperative pain and QoL after hemorrhoidectomy. Methods: This is a follow-up analysis of data derived from a multicenter randomized controlled trial including 770 patients, which examines the usefulness of tamponade after hemorrhoidectomy. Different pre-, intra-, and postoperative parameters were correlated with pain level assessed by NRS and QoL by the EuroQuol. Results: At univariate analysis, relevant (NRS > 5/10 pts.) early pain within 48 h after surgery was associated with young age (≤ 40 years, p = 0.0072), use of a tamponade (p < 0.0001), relevant preoperative pain (p = 0.0017), pudendal block (p < 0.0001), and duration of surgery (p = 0.0149). At multivariate analysis, not using a pudendal block (OR 2.64), younger age (OR 1.55), use of a tamponade (OR 1.70), and relevant preoperative pain (OR 1.56) were significantly associated with relevant early postoperative pain. Relevant pain on day 7 was significantly associated only with relevant early pain (OR 3.13, p < 0.001). QoL overall remained at the same level. However, n = 229 (33%) patients presented an improvement of QoL and n = 245 (36%) an aggravation. Improvement was associated with a reduction of pain levels after surgery (p < 0.0001) and analgesia with opioids (p < 0.0001). Conclusion: Early relevant pain affects younger patients but can be prevented by avoiding tamponades and using a pudendal block. Relevant pain after 1 week is associated only with early pain. Relief in preexisting pain and opioids improve QoL. Trial registration: DRKS00011590 12 April 2017.

Einleitung Für das lokal begrenzte Ösophaguskarzinom ist die multimodale Therapie aktuell der Goldstandard. Im Gegensatz dazu ist das metastasierte Ösophaguskarzinom als palliative Erkrankung definiert. Aktuell wird diesen Patienten lediglich eine Systemtherapie empfohlen. Dennoch steigt die Evidenz für den Nutzen einer multimodalen Therapie inklusive chirurgischer Resektion für das metastasierte Ösopohaguskarzinom. Ziel dieser Studie ist es, das Follow-Up von metastasierten Patienten mit einem Ösophaguskarzinom abhängig von ihrer individuellen Therapie zu untersuchen. Methodik Wir inkludierten 235 Patienten, die an unserem Zentrum aufgrund ihrer synchronen oder metachronen Metastasierung eines Ösophaguskarzinoms therapiert wurden. Alle inkludierten Patienten haben eine Ivor-Lewis-Ösophagusresektion erhalten. Den Patienten wurde jeweils ein individuelles Therapiekonzept nach Tumorboardkonferenz empfohlen. Ergebnis Die häufigste Metastasenlokalisation war die Leber, gefolgt von Lunge, distalen Lymphknoten und dem Peritoneum. 42 Patienten (17.9%) erhielten eine alleinige Resektion der Metastasen, 37 (15.7%) eine multimodale Therapie inklusive Resektion, 78 (33.2%) eine alleinige Chemotherapie, 49 (20.9%) eine sonstige Therapie sowie 29 (12.3%) Best-supportive-Care. In Überlebensanalysen konnten wir zeigen, dass Patienten, die eine multimodale Therapie inklusive Resektion erhalten haben, ein signifikant besseres Gesamtüberleben zeigten (medianes Gesamtüberleben: 22 Monate, p<0.001). Wir definierten eine lokale Therapie (Resektion oder Radiatio) mit oder ohne Systemtherapie einer einzelnen Metastase als kurativ intendierten Therapieansatz. Hier zeigte sich in multivariaten Analysen, dass eine kurativ intendierte Therapie ein signifikanter unabhängiger Faktor für ein besseres Patientenüberleben ist (HR=0.287, 95% CI=0.160-0.517, p<0.001). Zusätzlich zeigten sich eine höhere Anzahl an Metastasen sowie eine inkomplette Resektion des Primärtumors als unabhängige Risikofaktoren für ein schlechteres Überleben. Schlussfolgerung Diese retrospektive Studie konnte zeigen, dass eine Resektion von Metastasen des Ösophaguskarzinoms im Rahmen einer multimodalen Therapie eine machbare und in ausgewählten Patienten eine Therapieoption mit dem besten Gesamtüberleben ist. Zusätzlich konnte ein kurativ intendierter Therapieansatz für das metastasierte Ösophaguskarzinom beschrieben werden. Prospektive Studien sind notwendig, um genaue Auswahlkriterien definieren zu können. Article published online: 28 August 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Introduction: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2–directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC). Material and Methods: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship. Results: Of 598 human EACs analyzed, 88% showed varying degrees of TROP2 positivity. High TROP2 positive ESO-26 and low TROP2 positive OACM5.1C showed high sensitivity to SG in contrast to negative FLO-1. In vivo, the ESO-26 tumor shows a significantly better response to SG than the TROP2-negative FLO-1 tumor. ESO-26 vital tumor cells show similar TROP2 expression on all carcinoma cells as before therapy initiation, FLO-1 is persistently negative. Discussion: Our data suggest that sacituzumab govitecan is a new therapy option in esophageal adenocarcinoma and the TROP2 expression in irinotecan-naïve EAC correlates with the extent of treatment response by sacituzumab govitecan. TROP2 is emerging as a predictive biomarker in completely TROP2-negative tumors. This should be considered in future clinical trials.

Introduction: Despite modern multimodal therapeutic regimens, the prognosis of esophageal adenocarcinoma (EAC) is still poor and there is a lack of biological markers estimating the patients’ prognosis. Fructose-1,6-biphosphatase (FBP1) is a key enzyme in gluconeogenesis and is associated with tumor initiation in several cancers. Therefore, this study aims to characterize its implication for EAC patients. Methods and materials: A total of 571 EAC patients who underwent multimodal treatment between 1999 and 2017 were analyzed for FBP1 expression using immunohistochemistry. Results: 82.5% of the EACs show FBP1 expression in the tumor albeit with different intensities categorizing specimens accordingly into score 0 (no expression), score 1 (weak expression), score 2 (moderate expression) and score 3 (strong expression) (score 1 = 25.0%, score 2 = 35.9%, score 3 = 21.5%). Intratumoral FBP1 expression was significantly associated with a better prognosis (p = 0.024). This observation was particularly relevant among patients who received primary surgery without neoadjuvant treatment (p = 0.004). In multivariate analysis, elevated FBP1 expression was an independent biomarker associated with a favorable prognosis. Discussion: Despite being associated with a favorable prognosis, the majority of patients with high FBP1 expression also require individualized therapy options to ensure long-term survival. Recently, it has been shown that the presence of the FBP1 protein increases the sensitivity of pancreatic cancer cells to the bromodomain and extraterminal domain (BET) inhibitor JQ1. Conclusion: We described for the first time the prognostic and possibly therapeutic relevance of FBP1 in EAC. The efficiency of the BET inhibitor in EAC should be verified in clinical studies and special attention should be paid to the effects of neoadjuvant therapy on FBP1 expression.

Background: According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods: In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion: This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers: EudraCT 2019–002734-37; NCT04617457.