Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at advanced stages and most anti-cancer therapies have failed to substantially improve prognosis of PDAC patients. As a result, PDAC is still one of the deadliest tumors. Tumor heterogeneity, manifesting at multiple levels, provides a conclusive explanation for divergent survival times and therapy responses of PDAC patients. Besides tumor cell heterogeneity, PDAC is characterized by a pronounced inflammatory stroma comprising various non-neoplastic cells such as myofibroblasts, endothelial cells and different leukocyte populations which enrich in the tumor microenvironment (TME) during pancreatic tumorigenesis. Thus, the stromal compartment also displays a high temporal and spatial heterogeneity accounting for diverse effects on the development, progression and therapy responses of PDAC. Adding to this heterogeneity and the impact of the TME, the microbiome of PDAC patients is considerably altered. Understanding this multi-level heterogeneity and considering it for the development of novel therapeutic concepts might finally improve the dismal situation of PDAC patients. Here, we outline the current knowledge on PDAC cell heterogeneity focusing on different stromal cell populations and outline their impact on PDAC progression and therapy resistance. Based on this information, we propose some novel concepts for treatment of PDAC patients.

Recent developments in robotic surgery have led to an increasing number of robot-assisted hepatobiliary procedures. However, a limitation of robotic surgery is the missing haptic feedback. The fluorescent dye indocyanine green (ICG) may help in this context, which accumulates in hepatocellular cancers and around hepatic metastasis. ICG accumulation may be visualized by a near-infrared camera integrated into some robotic systems, helping to perform surgery more accurately. We aimed to test the feasibility of preoperative ICG application and its intraoperative use in patients suffering from hepatocellular carcinoma and metastasis of colorectal cancer, but also of other origins. In a single-arm, single-center feasibility study, we tested preoperative ICG application and its intraoperative use in patients undergoing robot-assisted hepatic resections. Twenty patients were included in the final analysis. ICG staining helped in most cases by detecting a clear lesion or additional metastases or when performing an R0 resection. However, it has limitations if applied too late before surgery and in patients suffering from severe liver cirrhosis. ICG staining may serve as a beneficial intraoperative aid in patients undergoing robot-assisted hepatic surgery. Dose and time of application and standardized fluorescence intensity need to be further determined.

Introduction: Robotic-assisted liver surgery (RALS) with its known limitations is gaining more importance. The fluorescent dye, indocyanine green (ICG), is a way to overcome some of these limitations. It accumulates in or around hepatic masses. The integrated near-infrared cameras help to visualize this accumulation. We aimed to compare the influence of ICG staining on the surgical and oncological outcomes in patients undergoing RALS. Material and Methods: Patients who underwent RALS between 2014 and 2021 at the Department of General Surgery at the University Hospital Schleswig-Holstein, Campus Kiel, were included. In 2019, ICG-supported RALS was introduced. Results: Fifty-four patients were included, with twenty-eight patients (50.9%) receiving preoperative ICG. Hepatocellular carcinoma (32.1%) was the main entity resected, followed by the metastasis of colorectal cancers (17%) and focal nodular hyperplasia (15.1%). ICG staining worked for different tumor entities, but diffuse staining was noted in patients with liver cirrhosis. However, ICG-supported RALS lasted shorter (142.7 ± 61.8 min vs. 246.4 ± 98.6 min, p < 0.001), tumors resected in the ICG cohort were significantly smaller (27.1 ± 25.0 mm vs. 47.6 ± 35.2 mm, p = 0.021) and more R0 resections were achieved by ICG-supported RALS (96.3% vs. 80.8%, p = 0.075). Conclusions: ICG-supported RALS achieve surgically and oncologically safe results, while overcoming the limitations of RALS.

Purpose: Postoperative pancreatic fistula (POPF) is a complication discussed in the context of pancreatic surgery, but may also result from splenectomy; a relationship that has not been investigated extensively yet. Methods: This retrospective single-center study aimed to analyze incidence of and risk factors for POPF after splenectomy. Patient characteristics included demographic data, surgical procedure, and intra- and postoperative complications. POPF was defined according to the International Study Group on Pancreatic Surgery as POPF of grade B and C or biochemical leak (BL). Results: Over ten years, 247 patients were identified, of whom 163 underwent primary (spleen-associated pathologies) and 84 secondary (extrasplenic oncological or technical reasons) splenectomy. Thirty-six patients (14.6%) developed POPF of grade B/C or BL, of which 13 occurred after primary (7.9%) and 23 after secondary splenectomy (27.3%). Of these, 25 (69.4%) were BL, 7 (19.4%) POPF of grade B and 4 (11.1%) POPF of grade C. BL were treated conservatively while three patients with POPF of grade B required interventional procedures and 4 with POPF of grade C required surgery. POPF and BL was noted significantly more often after secondary splenectomy and longer procedures. Multivariate analysis confirmed secondary splenectomy and use of energy-based devices as independent risk factors for development of POPF/BL after splenectomy. Conclusion: With an incidence of 4.5%, POPF is a relevant complication after splenectomy. The main risk factor identified was secondary splenectomy. Although POPF and BL can usually be treated conservatively, it should be emphasized when obtaining patients’ informed consent and treated at centers with experience in pancreatic surgery.

Esophagectomies are among the most invasive surgical procedures that highly influence health-related quality of life (HRQoL). Recent improvements have helped to achieve longer survival. Therefore, long-term postoperative HRQoL needs to be emphasized in addition to classic criterions like morbidity and mortality. We aimed to compare short and long-term HRQoL after open transthoracic esophagectomies (OTEs) and robotic-assisted minimally invasive esophagectomies (RAMIEs) in patients suffering from esophageal adenocarcinoma. Prospectively collected HRQoL-data (from the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-C30 (EORTC QLQ-C30)) were correlated with clinical courses. Only patients suffering from minor postoperative complications (Clavien–Dindo Classification of < 2) after R0 Ivor-Lewis-procedures were included. Age, sex, body mass index (BMI), American Society of Anesthesiologists physical status-score (ASA-score), tumor stage, and perioperative therapy were used for propensity score matching (PSM). Twelve RAMIE and 29 OTE patients met the inclusion criteria. RAMIE patients reported significantly better emotional and social function while suffering from significantly less pain and less physical impairment four months after surgery. The long-term follow up confirmed the results. Long-term postoperative HRQoL and self-perception partly exceeded the levels of the healthy reference population. Minor operative trauma by robotic approaches resulted in significantly reduced physical impairments while improving HRQoL and self-perception, especially in the long-term. However, further long-term results are warranted to confirm this positive trend.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages, limiting the prognoses of patients. Metastasis requires high tumor cell plasticity, implying phenotypic switching in response to changing environments. Here, epithelial–mesenchymal transition (EMT), being associated with an increase in cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC phenotypes exist along the EMT axis and how these impact malignancy-associated properties, we aimed to characterize CSC populations of epithelial and mesenchymal-like PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. The Panc1 Holoclone cells showed a mesenchymal-like phenotype, dominated by a high expression of the stemness marker Nestin, while the Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. The Panc89 Holoclone cells showed enhanced cell growth and a self-renewal capacity but slow cluster-like invasion. Contrarily, the Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, the Panc1 and Panc89 cell variants significantly differed regarding the number and size of metastases, as well as organ manifestation, leading to different survival outcomes. Overall, these data support the existence of different CSC phenotypes along the EMT axis in PDAC, manifesting different metastatic propensities.