Iron oxide nanoparticle-based hyperthermia is an emerging field in cancer treatment. The hyperthermia is primarily achieved by two differing methods: magnetic fluid hyperthermia and photothermal therapy. In magnetic fluid hyperthermia, the iron oxide nanoparticles are heated by an alternating magnetic field through Brownian and Néel relaxation. In photothermal therapy, the hyperthermia is mainly generated by absorption of light, thereby converting electromagnetic waves into thermal energy. By use of iron oxide nanoparticles, this effect can be enhanced. Both methods are promising tools in cancer treatment and are, therefore, also explored for gastrointestinal malignancies. Here, we provide an extensive literature research on both therapy options for the most common gastrointestinal malignancies (esophageal, gastric and colorectal cancer, colorectal liver metastases, hepatocellular carcinoma, cholangiocellular carcinoma and pancreatic cancer). As many of these rank in the top ten of cancer-related deaths, novel treatment strategies are urgently needed. This review describes the efforts undertaken in vitro and in vivo.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a meager prognosis due to its chemotherapy resistance. A new treatment method may be magnetic fluid hyperthermia (MFH). Magnetoliposomes (ML), consisting of superparamagnetic iron oxide nanoparticles (SPION) stabilized with a phospholipid-bilayer, are exposed to an alternating magnetic field (AMF) to generate heat. To optimize this therapy, we investigated the effects of MFH on human PDAC cell lines and 3D organoid cultures. Material and Methods: ML cytotoxicity was tested on Mia PaCa-2 and PANC-1 cells and on PDAC 3D organoid cultures, generated from resected tissue of patients. The MFH was achieved by AMF application with an amplitude of 40– 47 kA/m and a frequency of 270 kHz. The MFH effect on the cell viability of the cell lines and the organoid cultures was investigated at two different time points. Clonogenic assays evaluated the impairment of colony formation. Altering ML set-ups addressed differences arising from intra- vs extracellular ML locations. Results: Mia PaCa-2 and PANC-1 cells showed no cytotoxic effects at ML concentrations up to 300 μg(Fe)/mL and 225 μg(Fe)/mL, respectively. ML at a concentration of 225 μg(Fe)/mL were also non-toxic for PDAC organoid cultures. MFH treatment using exclusively extracellular ML presented the highest impact on cell viability. Clonogenic assays demonstrated remarkable impairment as long-term outcome in MFH-treated PDAC cell lines. Additionally, we successfully treated PDAC organoids with extracellular ML-derived MFH, resulting in notably reduced cell viabilities 2h and 24 h post treatment. Still, PDAC organoids seem to partly recover from MFH after 24 h as opposed to conventional 2D-cultures. Conclusion: Treatment with MFH strongly diminished pancreatic cancer cell viability in vitro, making it a promising treatment strategy. As organoids resemble the more advanced in vivo conditions better than conventional 2D cell lines, our organoid model holds great potential for further investigations.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its consequences represent a growing global health burden that urgently requires physiologically relevant in vitro models beyond conventional 2D culture systems. In this study, we report the successful establishment of 45 patient-derived liver organoid lines. These organoids were generated from healthy, steatotic and cirrhotic tissues collected from 207 liver surgeries at RWTH University Hospital Aachen, with an initiation success rate of 82%. The organoids were propagated for at least six passages using an optimized protocol. Multiplex immunofluorescence analysis revealed highly proliferative structures with approximately 40% Ki-67-positive cells expressing hepatocyte (Albumin and HNF4α) and cholangiocyte (CK19) markers. Intermittent LGR5 staining suggested the presence of liver progenitor cell features. Quantitative PCR results confirmed variable HNF4α expression, indicating inter-patient heterogeneity in differentiation status. Time-lapse imaging combined with mathematical modeling uncovered a biphasic growth dynamic with an initial linear expansion in the first 15 h, followed by exponential growth (doubling time ≈ 20.6 h) between 30 and 72 h. Overall, our workflow produced genetically and phenotypically stable liver organoids that recapitulate essential features of various hepatic conditions. This provides a solid foundation for disease modeling, potential drug testing, and quantitative systems biology.

Introduction: Multidisciplinary tumor boards (MTBs) are the standard for oncologic decision-making but require substantial time and personnel resources. Large language models (LLMs) may support MTBs by generating structured, guideline-based recommendations. We evaluated concordance between MTB decisions and LLM recommendations in newly diagnosed cholangiocellular adenocarcinoma (CCA) and hepatocellular carcinoma (HCC). Method: In this retrospective single-center study, MTB protocols from 2022–2023 were screened. After exclusions, 50 CCA and 50 HCC cases were analyzed. Institutional MTB recommendations were compared with outputs from ChatGPT and Claude using identical structured clinical summaries available at the time of MTB presentation. Agreement was assessed using Cohen’s kappa, and correlation using Spearman’s rank coefficient. Results: For CCA, exact concordance between MTB and ChatGPT was 80%, with substantial agreement (k = 0.688) and strong correlation (r = 0.725; both p < 0.001). Concordance with Claude was at 56%. For HCC, concordance between MTB and ChatGPT was 66%, with substantial agreement (k = 0.604) and moderate correlation (r = 0.484; both p < 0.001). Concordance with Claude was only 38%, with fair agreement (k = 0.314, p < 0.001) and weak correlation (r = 0.086, p = 0.551). Conclusions: LLM-derived recommendations varied markedly by model. ChatGPT demonstrated substantial concordance, whereas Claude showed limited agreement. MTBs appeared more individualized, while LLM outputs were more guideline-oriented. These findings highlight the potential role of LLMs as supportive tools for structured clinical reasoning and guideline adherence. Prospective multicenter studies should evaluate real-time LLM integration into MTB workflows, efficiency, decision quality, and patient outcomes safely.

Introduction: Necrotizing pancreatitis (NP), a severe form of acute pancreatitis (AP), is linked to lower survival rates. Treatment strategies have shifted towards less invasive, step-up approaches, favoring minimally invasive procedures. In this study, we report on the potential of combining the minimally invasive surgical approach with endoscopic necrosectomy as a novel treatment strategy, termed serial percutaneous endoscopic necrosectomy (SPEN), for patients with therapy-refractory NP. Material and Methods: A cohort of 19 patients suffering from therapy-refractory NP, defined as persistent necroses after drainage treatment and subsequent video-assisted retroperitoneal debridement (VARD), was treated with SPEN upon failure of the above stated. In contrast to surgery, SPEN does not require general anesthesia or an operating theater. The results were compared with the current data on alternative treatments. Results: The investigated cohort consisted of severely ill patients as most patients experienced organ failure as well as severe disease progression in need of intensive-care unit admission. SPEN was performed 4.3 ± 3.8 times, ranging from 1 to 14 procedures per individual. According to the current Clavien–Dindo classification, only “mild” and no major SPEN procedure-associated complications can be observed. Conclusion: In this report, we present our experience with a novel treatment approach combining surgery and endoscopic interventions for the treatment of NP. While sparing resources, SPEN was shown to be safe and effective. Favorable implications are implied owing to the combination of the best of two worlds: surgery, with its capacity for extensive necrosectomy and endoscopic necrosectomy, which is valued for its applicability as a flexible, low-grade invasive but effective tool that may be dynamically employed depending on individual disease progression.

Background: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT), representing a curative treatment option for selected patients. A remaining clinical challenge is the recurrence of HCC after transplantation, impacting long-term graft and patient survival. The impact of different bridging therapies (BTs) such as transarterial chemoembolization (TACE), local ablation or liver resection on recurrence rates remains unclear. We assessed post-transplant HCC recurrence and survival focusing on the role of pre-transplant bridging therapies. Methods: Adult recipients undergoing LT for HCC at Hannover Medical School from January 2007 to September 2022 were retrospectively analyzed (n = 185). Recurrence was defined as confirmed intra or extrahepatic HCC after LT. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier estimation and log-rank testing; multivariable Cox proportional hazards regression was used to identify independent factors influencing OS. Results: Pre-transplant BT was administered in 85.4% of patients, consisting of only TACE, (n = 20; 10.8%), local ablation, (n = 32; 17.3%), liver resection (n = 27; 14.6%) or a multimodal approach (n = 50; 27%). Post-transplant HCC recurrence rate was 9.2% with a median time to recurrence of 845 days (range 126–3978 days). Patients with post-transplant HCC recurrence had a significantly higher prevalence of viral hepatitis (70.6% vs. 57.1%; p = 0.01), higher pre-transplant AFP peak levels (37.5 vs. 10 ng/mL; p = 0.03), larger tumor sizes (median 3.95 cm vs. 2.6 cm; p = 0.03) and more poorly differentiated tumors (G3; 25.0% vs. 5.3%, p = 0.04). Kaplan–Meier analysis showed significant overall differences in OS and RFS among bridging therapy groups (p = 0.03). In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE (p = 0.035). Last measured pre-transplant AFP < 15 ng/mL was a significant predictor of both improved OS (p = 0.006) and RFS (p = 0.008), whereas peak AFP did not reach significance after correction. Multivariable Cox regression revealed HCC recurrence, high recipient BMI and low LabMELD as independently associated with reduced OS after LT. Median OS after HCC recurrence was 13 months. Conclusions: Our monocentric retrospective data indicate that post-transplant HCC recurrence is uncommon but remains a challenge regarding life expectancy and is influenced by pre-transplant bridging therapy. In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE. Last measured pre-transplant AFP < 15 ng/mL was associated with both improved OS and RFS, suggesting that treatment response may also represent a prognostically relevant factor. Further prospective validation of contemporary locoregional and systemic bridging approaches, especially in the context of tumor biology and treatment response, is warranted.