Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are both deadly cancers and they share many biological features besides their close anatomical location. One of the main histological features is neurotropism, which results in frequent perineural invasion. The underlying mechanism of cancer cells favoring growth by and through the nerve fibers is not fully understood. In this review, we provide knowledge of these cancers with frequent perineural invasion. We discuss nerve fiber crosstalk with the main different components of the tumor microenvironment (TME), the immune cells, and the fibroblasts. Also, we discuss the crosstalk between the nerve fibers and the cancer. We highlight the shared signaling pathways of the mechanisms behind perineural invasion in PDAC and CCA. Hereby we have focussed on signaling neurotransmitters and neuropeptides which may be a target for future therapies. Furthermore, we have summarized retrospective results of the previous literature about nerve fibers in PDAC and CCA patients. We provide our point of view in the potential for nerve fibers to be used as powerful biomarker for prognosis, as a tool to stratify patients for therapy or as a target in a (combination) therapy. Taking the presence of nerves into account can potentially change the field of personalized care in these neurotropic cancers.

The risk score showed a high accuracy to predict major complications after PD based on preoperative parameters only. This simple and quick approach allows for individualized risk assessment and may improve preoperative counselling and patient selection for perioperative treatment strategies.

BackgroundTumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma.MethodsWe analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients’ survival. Statistical analysis was performed using SPSS software.ResultsPatients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6 % vs. 75.1 %; three-year 61.3 % vs. 42.4 %; both ρ < 0.05) and recurrence-free survival (one-year 93.9 % vs. 57.4 %; three-year 59.8 % vs. 26.2 %; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05).ConclusionsOverall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs.

Background The goal of our study was to evaluate the current approach in prediction of postoperative major complications after pancreaticoduodenectomy (PD), especially symptomatic pancreatic fistula (POPF), using parameters derived from computed tomography (CT). Methods Patients after PD were prospectively collected in a database of the local department of surgery and all patients with CT scans available were assessed in this study. CT parameters were measured at the level of the intervertebral disc L3/L4 and consisted of the areas of the visceral adipose tissue (A VAT ), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (A MVEN ), psoas muscle (A MPSO ), paraspinal muscle (A MSPI ), total muscle (A MTOT ), as well as the mean muscle attenuation (MA) and skeletal muscle index (SMI). Mann-Whitney-U Test for two independent samples and binary logistic regression were used for statistical analysis. Results One hundred thirty-nine patients (55 females, 84 males) were included. DPD was 2.9 mm (Range 0.7–10.7) on median and more narrow in patients with complications equal to or greater stadium IIIb ( p < 0.04) and severe POPF ( p < 0.01). DPP median value was 17 (6.9–37.9) mm and there was no significant difference regarding major complications or POPF. A VAT showed a median value of 127.5 (14.5–473.0) cm 2 and was significantly larger in patients with POPF ( p < 0.01), but not in cases of major complications ( p < 0.06). A MPSO , A MSPI , A MVEN and A MTOT showed no significant differences between major complications and POPF. MA was both lower in groups with major complications ( p < 0.01) and POPF ( p < 0.01). SMI failed to differentiate between patients with or without major complications or POPF. Conclusion Besides the known factors visceral obesity and narrowness of the pancreatic duct, the mean muscle attenuation can easily be examined on routine preoperative CT scans and seems to be promising parameter to predict postoperative complications and POPF.