Alterations of body composition, especially decreased muscle mass (sarcopenia) and impaired muscle quality (myosteatosis), are associated with inferior outcomes in various clinical conditions. The data of 100 consecutive patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) at a German university medical centre were retrospectively analysed (May 2008–December 2019). Myosteatosis and sarcopenia were evaluated using preoperative computed-tomography-based segmentation. We investigated the predictive role of alterations in body composition on perioperative morbidity, mortality and long-term oncological outcome. Myosteatotic patients were significantly inferior in terms of major postoperative complications (Clavien–Dindo ≥ 3b; 25% vs. 5%, p = 0.007), and myosteatosis could be confirmed as an independent risk factor for perioperative morbidity in multivariate analysis (odds ratio: 6.184, confidence interval: 1.184–32.305, p = 0.031). Both sarcopenic and myosteatotic patients received more intraoperative blood transfusions (1.6 ± 22 vs. 0.3 ± 1 units, p = 0.000; 1.4 ± 2.1 vs. 0.3 ± 0.8 units, respectively, p = 0.002). In terms of long-term overall and recurrence-free survival, no statistically significant differences could be found between the groups, although survival was tendentially worse in patients with reduced muscle density (median survival: 41 vs. 60 months, p = 0.223). This study confirms the prognostic role of myosteatosis in patients suffering from HCC with a particularly strong value in the perioperative phase and supports the role of muscle quality over quantity in this setting. Further studies are warranted to validate these findings.
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). 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 (AVAT), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (AMVEN), psoas muscle (AMPSO), paraspinal muscle (AMSPI), total muscle (AMTOT), 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. 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. AVAT showed a median value of 127.5 (14.5–473.0) cm2 and was significantly larger in patients with POPF (p < 0.01), but not in cases of major complications (p < 0.06). AMPSO, AMSPI, AMVEN and AMTOT 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. 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.
B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.
27 February 2019 in Alimentary Pharmacology & Therapeutics
Summary: Background: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis‐associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity.Aim: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT).Methods: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine‐mediated cancer pathways inclusive of MAPK and NF‐kappa B were tested.Results: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1‐40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12‐0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029).Conclusions: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine‐A2AR mediated growth‐promoting effects on HCC cells.
Background and Aims: Perihilar cholangiocarcinoma (pCCA) is a hepatobiliary malignancy, with a dismal prognosis. Nerve fiber density (NFD)—a novel prognostic biomarker—describes the density of small nerve fibers without cancer invasion and is categorized into high numbers and low numbers of small nerve fibers (high vs low NFD). NFD is different than perineural invasion (PNI), defined as nerve fiber trunks invaded by cancer cells. Here, we aim to explore differences in immune cell populations and survival between high and low NFD patients. Approach and Results: We applied multiplex immunofluorescence (mIF) on 47 pCCA patients and investigated immune cell composition in the tumor microenvironment (TME) of high and low NFD. Group comparison and oncological outcome analysis was performed. CD8+PD-1 expression was higher in the high NFD than in the low NFD group (12.24 × 10−6 vs. 1.38 × 10−6 positive cells by overall cell count, p = 0.017). High CD8+PD-1 expression was further identified as an independent predictor of overall (OS; Hazard ratio (HR) = 0.41; p = 0.031) and recurrence-free survival (RFS; HR = 0.40; p = 0.039). Correspondingly, the median OS was 83 months (95% confidence interval (CI): 18–48) in patients with high CD8+PD-1+ expression compared to 19 months (95% CI: 5–93) in patients with low CD8+PD-1+ expression (p = 0.018 log rank). Furthermore, RFS was significantly lower in patients with low CD8+PD-1+ expression (14 months (95% CI: 6–22)) compared to patients with high CD8+PD-1+ expression (83 months (95% CI: 17–149), p = 0.018 log rank). Conclusions: PD-1+ T-cells correlate with high NFD as a prognostic biomarker and predict good survival; the biological pathway needs to be investigated.
8 October 2018 in Zeitschrift für Gastroenterologie
Introduction There are several well-established surgical procedures for the treatment of chronic pancreatitis (CP). The present study seeks to evaluate the perioperative and long-term outcome of these procedures. Methods All patients who had undergone pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR), and distal pancreatectomy (DP) for CP were retrospectively analyzed with regards to the perioperative outcome and long-term survival. Health-related quality of life (HRQoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Results There were 145 patients available for analysis. Major complications (grade IIIb–V) occurred in 19 %, in-hospital mortality was 4.2 %, and 90-day mortality was 3 % with no differences between the different resection groups (all p > 0.05). Ten-year survival was 58 % and was highest in the DP group (100 %) but without statistical significance (p = 0.72). The response rate of the HRQoL assessment was 45 % (65 of 145). There was a significant improvement with regards to pain and HRQoL of all resection groups compared to the preoperative group (all p < 0.05). With respect to HRQoL and pain relief, the PD, DPPHR, and DP did not differ significantly. Discussion Surgical therapy of CP can be performed safely. The 3 different types of resection performed equally with regards to complications and HRQoL.