Verbesserung der Ergebnisse nach Pankreas- und Leberresektionen

Es wird erwartet, dass das duktale Adenokarzinom des Pankreas bis 2030 zu den führenden Ursachen malignombedingter Mortalität zählt. Trotz intensiver Bemühungen ist das Survival bis heute nicht zufriedenstellend. Daher sind neue Ansätze zur Verbesserung des Überlebens dieser Patienten notwendig. Weiterhin ist die Major-Morbidität nach resezierenden Eingriffen des Pankreas, insbesondere bei Patienten mit Pankreaskarzinom, weiterhin hoch und erreicht bis zu 20% [33]. Die Arbeiten dieses Habilitationsprojektes sollen daher das Survival von Patienten nach Resektion von Pankreaskarzinomen verbessern sowie Morbidität und Mortalität nach Pankreaseingriffen senken. In diesem Zusammenhang untersucht dieses Habiliationsprojekts inwieweit durch Veränderungen der prä- und postoperativen Therapie das Outcome von Patienten mit Pankreaskarzinom verbessert werden kann. Präoperativ wird aktuell versucht, mit neoadjuvanten Chemotherapiekonzepten vormals irresektablen Patienten mit grenzwertig resektablen und lokal fortgeschrittenen Befunden eine kurative Entfernung ihres Tumors zu ermöglichen Hier zeigen die multizentrischen Daten dieses Habilitationsprojektes, dass eine präoperative Chemotherapie mit FOLFIRINOX mit einer Resektionsrate von 76.3% und complete response rate von 10.7% verbunden ist. Diese Daten sind insbesondere vor dem Hintergrund ermutigend, dass Patienten mit lokal fortgeschrittenen Befunden vor der Einführung neoadjuvanter Therapiekonzepte einer palliativen Behandlung zugeführt wurden. Zusätzlich scheinen diese präoperativen Therapieschemata auch bei gut selektionierten älteren Patienten mit zu jüngeren vergleichbaren Ergebnissen anwendbar zu sein. Für die postoperative Therapie zeigt dieses Projekt, dass eine Besiedelung des Gallenganges mit K. pneumoniae eine adjuvante Therapie mit Gemcitabine ineffektiv macht und K. pneumoniae-negative Patienten dagegen einen deutlichen Survival-Benefit durch adjuvantes Gemcitabine erfahren. Diese Daten sind in Einklang mit den Ergebnissen anderer Gruppen, die auf experimenteller Ebene zeigen konnten, dass K. pneumoniae wie andere Gammaproteobakterien die Cytidindeaminase exprimiert, ein Enzym, das Gemcitabine abbaut. Neben dem Einfluss des Mikrobioms auf das postoperative Patientenoutcome lässt sich die postoperative Rekonvaleszenz auch durch Modulation der Patientenerwartung an ihre Verweildauer verbessern. Als Teil dieses Habilitationsprojekts wurde im Rahmen einer prospektiven Studie untersucht, inwieweit die präoperative Suggestion einer kürzeren Verweildauer zu einer schnelleren postoperativen Rekonvaleszenz führt. Hier zeigte sich, dass Patienten, denen präoperativ eine kürzere Verweildauer genannt wurde, signifikant schneller objektive Entlasskriterien erreichten. Über die Zeit scheinen diese und andere graduellen Veränderungen das postoperative Survival nach Pankreaseingriffen zu verbessern. So konnte eine diesem Habilitationsprojekt zugehörige Meta-Regression zeigen, dass das postoperative Survival sich unabhängig von der Art der gegebenen Chemotherapie in den randomisiert-prospektiven Studien zur adjuvanten Chemotherapie über die Zeit verbesserte. Dies kann zum einen durch Optimierungen des operativen Eingriffs selbst, aber auch durch Verbesserungen perioperativer, chirurgischer Therapiestrategien interpretiert werde

The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation

Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic

ChatGPT's Gastrointestinal Tumor Board Tango: A limping dance partner?

Objectives: This study aimed to assess the consistency and replicability of treatment recommendations provided by ChatGPT 3.5 compared to gastrointestinal tumor cases presented at multidisciplinary tumor boards (MTBs). It also aimed to distinguish between general and case-specific responses and investigated the precision of ChatGPT’s recommendations in replicating exact treatment plans, particularly regarding chemotherapy regimens and follow-up protocols. Material and methods: A retrospective study was carried out on 115 cases of gastrointestinal malignancies, selected from 448 patients reviewed in MTB meetings. A senior resident fed patient data into ChatGPT 3.5 to produce treatment recommendations, which were then evaluated against the tumor board’s decisions by senior oncology fellows. Results: Among the examined cases, ChatGPT 3.5 provided general information about the malignancy without considering individual patient characteristics in 19% of cases. However, only in 81% of cases, ChatGPT generated responses that were specific to the individual clinical scenarios. In the subset of case-specific responses, 83% of recommendations exhibited overall treatment strategy concordance between ChatGPT and MTB. However, the exact treatment concordance dropped to 65%, notably lower in recommending specific chemotherapy regimens. Cases recommended for surgery showed the highest concordance rates, while those involving chemotherapy recommendations faced challenges in precision. Conclusions: ChatGPT 3.5 demonstrates potential in aligning conceptual approaches to treatment strategies with MTB guidelines. However, it falls short in accurately duplicating specific treatment plans, especially concerning chemotherapy regimens and ollow-up procedures. Ethical concerns and challenges in achieving exact replication necessitate prudence when considering ChatGPT 3.5 for direct clinical decision-making in MTBs

Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry

BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4–11] vs. 12 [10–18], 12 [8–19] or 12 [9–17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien–Dindo grade ≥ IIIa) complications (OR 0.49 [95% CI 0.25–0.96], P = 0.037), whereas—compared to exploration only—biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48–8.64], P = 0.005; 3.50 [1.39–8.81], P = 0.008; 4.96 [2.15–11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12893-022-01833-3

The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship

Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic strategies using stroma-depleting drugs have yielded disappointing results, an increasing body of research indicates the ECM may offer a variety of potential therapeutic targets. As preclinical studies of ECM-targeted drugs have shown promising effects, a number of clinical trials are currently investigating agents with the potential to advance the future treatment of PDAC. Thus, the present review seeks to give an overview of the complex relationship between the ECM and PDAC

En-bloc resection of a giant retroperitoneal lipoma: a case report and review of the literature

Background Retroperitoneal lipomas are an extremely rare condition with only 17 cases described in the literature since 1980. They can reach enormous size and cause significant abdominal symptoms. The most important differential diagnosis is the well-differentiated liposarcoma, which preoperatively often may not definitely be ruled out. Case presentation We present the case of a 73 year-old Caucasian patient with a giant retroperitoneal lipoma of 9 kg measuring 55 cm in diameter. The patient presented with abdominal pain and swelling that had been slowly progressive for the last 15 years. On computerized tomography an immense retroperitoneal tumor was revealed. Intraoperatively, the tumor did not show any signs of infiltrative growth, therefore sole tumor extirpation was performed. Conclusion Retroperitoneal lipomas are not clearly distinguishable from well-differentiated liposarcomas on imaging and even biopsies may be misleading. Moreover, abdominal symptoms, i.e. pain, obstipation and dysphagia may occur due to mechanical displacement. Therefore, surgical exploration with complete oncological resection is the therapy of choice if malignity cannot be ruled out

Quantitative Characterization of Ectopic Adrenal Gene Expression in Fetal Testes in 21-Hydroxylase Deficient Mice

Testicular adrenal rest tumors (TART) are a frequent and fertility impairing long-term complication in males with classic congenital adrenal hyperplasia. Due to lack of clear experimental data on their origin, they are hypothesized to be derived from ectopic adrenocortical cells within testicular tissue mainly growing upon stimulation by chronically elevated levels of adrenocorticotropin (ACTH). Alternatively, a more totipotent embryological origin has been discussed as the potential source of these tumors. The aim of this study was to quantify alterations of ectopic expression of adrenocortical genes (CYP11B1, CYP11B2, CYP21, MC2R) and the Leydig cell specific marker (INSL3) in testicular tissue of fetal 21-hydroxylase deficient (21OHD) mice. Timed-pregnancy studies were performed using H-2aw18 (aw18)-mice. Testes and adrenals of E15.5 and E18.5 mouse fetuses were used for real-time PCR and immunohistochemistry. Gene expression levels were analyzed for genotype-dependent alterations and compared with immunohistochemistry. While enzymes of steroidogenesis showed a significant increased expression in adrenals of 21OHD mice at both E15.5 and E18.5 compared to wild-type (WT) mice, expression levels were unaltered in testes of 21OHD mice. When compared to WT adrenals a significant increase of INSL3 expression in adrenals of 21OHD mice at E15.5 and E18.5 was detected. Cells with adrenocortical properties in mice fetal testis differ from in situ adrenocortical cells in gene expression and growth at E15.5 and E18.5. These findings suggest that the different local regulation and different local niche in adrenals and testes influence growth of aberrant adrenal cells