Current therapies for treating pancreatic ductal adenocarcinoma (PDAC) are largely ineffective, with the desmoplastic environment established within these tumors being considered a central issue. We established a 3D spheroid co-culture in vitro model using a PDAC cell line (either PANC-1 or Capan-2), combined with stellate cells freshly isolated from pancreatic tumors (PSC) or hepatic lesions (HSC), and human type I collagen to analyze the efficiency of the chemotherapeutic gemcitabine (GEM) as well as two novel drug candidates derived from natural products: pseudopterosin (PsA-D) and O-methyltylophorinidine (TYLO). Traditional 2D in vitro testing of these agents for cytotoxicity on PANC-1 demonstrated IC₅₀ values of 4.6 (±0.47) nM, 34.02 (±1.35) µM, and 1.99 (±0.13) µM for Tylo, PsA-D, and GEM, respectively; these values were comparable for Capan-2: 5.58 (±1.74) nM, 33.94 (±1.02) µM, and 0.41 (±0.06) µM for Tylo, PsA-D, and GEM, respectively. Importantly, by assessing the extent of viable cells within 3D co-culture spheroids of PANC-1 with PSC or HSC, we could demonstrate a significant lack of efficacy for GEM, while TYLO remained active and PsA-D showed slightly reduced efficacy: GEM in PANC-1/PSC (IC₅₀ = >100 µM) or PANC-1/HSC (IC₅₀ = >100 µM) spheroids, TYLO in PANC-1/PSC (IC₅₀ = 3.57 ± 1.30 nM) or PANC-1/HSC (IC₅₀ = 6.39 ± 2.28 nM) spheroids, and to PsA-D in PANC-1/PSC (IC₅₀ = 54.42 ± 12.79 µM) or PANC-1/HSC (IC₅₀ = 51.75 ± 0.60 µM). Microscopic 3D rendering supported these cytotoxicity outcomes, showing little or no morphological spheroid structure change during this period of rapid cell death. Our results support the use of this 3D spheroid co-culture in vitro model having a desmoplastic microenvironment for the identification of possible novel chemotherapeutic drug candidates for PDAC, such as TYLO and PsA-D.

Esophageal surgery is deemed one of the most complex visceral operations. There is a well-documented correlation between higher caseload and better outcomes, with hospitals that perform more surgeries experiencing significantly lower mortality rates. The approach to caseload per year varies across different countries within Europe. Germany increased the minimum annual required caseload of complex esophageal surgeries from 10 to 26 starting in 2023. Furthermore, the new regulations present challenges for surgical training and staff recruitment, risking the further fragmentation of training programs. Enhanced regional cooperation is proposed as a solution to ensure comprehensive training. This review explores the benefits of robotic-assisted minimally invasive esophagectomy (RAMIE) in improving surgical precision and patient outcomes and aims to evaluate how the caseload per year influences the quality of patient care and the efficacy of surgical training, especially with the integration of advanced robotic techniques.

Background/Objectives: Pelvic exenteration (PE) might be a curative option for patients with advanced pelvic malignancies. Due to its significant morbidity and mortality rates, PE necessitates meticulous patient selection, and a comprehensive understanding of disease spread. This study outlines the experience at a single tertiary referral center and investigates prognostic factors influencing survival post-PE, thereby guiding clinical decision-making processes. Methods: Patients undergoing PE for advanced pelvic gynecological malignancies between 01/2016 and 12/2023 were retrospectively analyzed using a prospectively managed database. Eligibility for PE was determined through individualized tumor board evaluations based on CT/MRI imaging, excluding patients with distant metastases. Baseline demographic and clinical characteristics, operative details, complication rates, and histopathological findings were assessed using univariate and multivariate regression analyses. Disease-free (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. Poor outcome prognostic factors were identified, outlining an optimal candidate profile for PE. Results: A total of 70 patients were included. The median age was 54.5 years. Forty-three patients (61.4%) presented with recurrent disease and the majority were diagnosed with cervical cancer (n = 48, 68.6%). Total PE was performed in 40 patients (57.1%), with complete tumor resection achieved in 68.6% of patients (n = 48). Sixteen patients (22.8%) experienced grade IV/V complications. Median DFS and OS were 8.2 and 16.4 months, respectively. Multivariate analysis identified R1 resection status and para-aortic lymph node involvement as independent negative prognostic factors. Conclusions: PE is a viable option for selected patients with advanced primary and recurrent pelvic gynecological malignancies. When complete tumor resection is feasible, patients may derive benefit from PE, although the risk of severe perioperative complications must be carefully evaluated.

Background: According to current guidelines, preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting (ERCP/stenting) is often necessary in patients with obstructive jaundice due to pancreatic ductal adenocarcinoma (PDAC), including severe jaundice (bilirubin > 250 umol/l), pruritus, cholangitis, cholestatic liver dysfunction, renal failure, severe malnutrition, or delayed surgery for tumors requiring neoadjuvant chemotherapy. We aimed to investigate the impact of preoperative ERCP/stenting on postoperative and long-term outcomes following pancreaticoduodenectomy (PD) for PDAC. Methods: Clinicopathological data of patients who underwent partial/total PD for PDAC between 2012 and 2019 in two hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We compared patients treated with preoperative ERCP/stenting with those directly undergoing surgery according to postoperative morbidity, postoperative mortality, overall survival (OS) and disease-free survival (DFS). Results: During the study period, 192 patients underwent partial/total PD for PDAC. ERCP/stenting was performed in 105 patients, and 87 patients underwent resection without prior intervention. Postoperative 90-day overall morbidity rate (71% vs. 56%, p = 0.029) and superficial surgical site infection (SSI) rate (39% vs. 17%, p < 0.001) were significantly worse following preoperative ERCP/stenting. Major postoperative morbidity rate (18% vs. 21%, p = 0.650), organ/space SSI rate (7% vs. 14%, p = 0.100), and 90-day postoperative mortality rate (4% vs. 2%, p = 0.549) did not significantly differ between the two groups. After excluding 44 patients for whom the indication for ERCP/stenting was not consistent with current guidelines, ERCP/stenting was associated with a higher superficial SSI rate (36% vs. 17%, p = 0.009) and shorter length of stay (12 vs. 16 days, p = 0.004). Median OS (ERCP/stenting: 18 months vs. no ERCP/stenting: 23 months, p = 0.490) and median DFS (ERCP/stenting: 14 months vs. no ERCP/stenting: 18 months, p = 0.645) were independent from the utilization of ERCP/stenting. Conclusions: Preoperative ERCP/stenting in patients with PDAC can be performed without increasing organ/space SSI, major perioperative morbidity, and mortality rates and without worsening oncologic outcomes. However, it is associated with higher superficial SSI rates. If ERCP/stenting is not performed routinely but according to current guidelines, it is also associated with a shorter length of hospital stay. Further refinement of the indications for preoperative ERCP/stenting may reduce superficial SSI rates.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with no precise method for early detection. Circulating tumor cells (CTCs) expressing the dynamic polarity of the cytoskeletal membrane protein, ezrin, have been proposed to play a crucial role in tumor progression and metastasis. This study investigated the diagnostic and prognostic potential of polarized circulating tumor cells (p-CTCs) in HCC patients. CTCs were isolated from the peripheral blood of 20 HCC patients and 18 patients with nonmalignant liver disease (NMLD) via an OncoQuick^® kit and immunostained with Ezrin-Alexa Fluor 488^®, CD146-PE, and CD45-APC. A fluorescence microscopy was then performed for analysis. The HCC group exhibited significantly higher levels of p-CTCs, with median values of 0.56 p-CTCs/mL, compared to 0.02 p-CTCs/mL (p = 0.03) in the NMLD group. CTCs were detected in 95% of the HCC patients, with a sensitivity of 95% and specificity of 89%. p-CTCs were present in 75% of the HCC patients, with a sensitivity of 75% and a specificity of 94%. Higher p-CTC counts were associated with the significantly longer overall survival in HCC patients (p = 0.05). These findings suggest that p-CTCs could serve as valuable diagnostic and prognostic markers for HCC. The incorporation of p-CTCs into diagnostic strategies could enhance therapeutic decision-making and improve patient outcomes.

Robotic surgery has expanded minimally invasive options but introduces specific vulnerabilities during intraoperative emergencies. The physical separation of the surgeon from the patient, restricted access due to docking, and dependence on complex technology can delay life‑saving interventions if teams are not prepared. This review summarizes current evidence and expert practice on emergency management along the perioperative pathway in robotic surgery, focusing on a structured, systems‑based salvage strategy. Key domains include preoperative planning, classification of recoverable and non‑recoverable errors, and standardized protocols for rapid undocking, conversion, hemorrhage control, and resuscitation. Particular emphasis is placed on human factors, including visible name tags, closed‑loop communication, and structured briefings to strengthen situational awareness and role clarity in crises. Simulation‑based curricula and high‑fidelity in situ drills are highlighted as essential for rehearsing rare but high‑impact events such as catastrophic bleeding, cardiorespiratory collapse, or robotic system failure. In parallel, technology‑driven tools such as surgeon‑controlled suction, advanced vessel sealing, and artificial‑intelligence–assisted monitoring are discussed as adjuncts for earlier recognition and standardized documentation of critical events. Integrating these elements into protocolized workflows can improve preparedness, shorten response times, and support safer decision‑making when seconds matter in robotic surgery.