In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs’ hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

In this network meta-analysis, LHM demonstrated superior short- and long-term efficacy and should be considered first-line treatment of esophageal achalasia.

SUMMARYBackground: Hepatocellular carcinoma (HCC) has an incidence of 5-10 per 100 000 persons per year in the Western world. In 20% of cases, surgical liver resection (LR) or liver transplantation (LT) can be performed. LT results in longer survival, as it involves resection not only of the tumor, but of precancerous tissue as well. The optimal allocation of donor organs depends on the identification of patients for whom LR is adequate treatment. In this meta-analysis, we compare LT and LR for patients with early HCC and wellcompensated cirrhosis.

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3+ (p = 0.016) and CD8+ (p = 0.028) independently predicted better OS and DFS, respectively. CD20+ showed a trend towards better DFS (p = 0.076). Scoring of CD3+, CD8+, and CD20+ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3+ cells is an independent predictor of better OS, and CD8+ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

BackgroundmTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. The effect of mTOR-Is on the overall incidence of tumors irrespective of their origin is not entirely clear. Furthermore, conflicting data have been shown on mortality under mTOR-Is.MethodsThe current literature was searched for prospective randomized controlled renal transplantation trials. There were 1415 trials screened of which 13 could be included (pts. = 5924). A minimum follow-up of 24 months was mandatory for inclusion. Incidence of malignancies and patient survival was assessed in meta-analyses.ResultsThe average follow-up of all trials was 40.6 months. Malignancy was significantly reduced under mTOR-Is compared to CNIs (RR 0.70, CI 0.49–0.99, p = 0.046). This effect remained stable when combined with CNIs (RR 0.58, CI 0.34–1.00, p = 0.05). When NMSCs were excluded the risk for malignancy remained significantly reduced under mTOR-I therapy (mono and combi) (RR 0.43, CI 0.24–0.77, p = 0.0046). Graft survival was minimally decreased under mTOR-Is (RR 0.99, CI 0.98–1.00, p = 0.054). This effect was abrogated when mTOR-Is were combined with CNIs (RR 0.99, CI 0.97–1.02, p = 0.50). Patient survival was not different (RR 1.00, CI 0.99–1.01, p = 0.54).ConclusionsPosttransplant patients have a lower incidence of malignancy when treated with an mTOR-I no matter if it is used in combination with CNIs or not. This beneficial effect remains significant even when NMSCs are excluded. With currently used mTOR-I-based regimen patient and graft survival is not different compared to CNI therapies.

COVID-19 pandemic: implications on the surgical treatment of gastrointestinal and hepatopancreatobiliary tumours in EuropeEditor a Ongoing treatment. b Patient referral. c Suspended gastrointestinal (GI) and hepatopancreatobiliary (HPB) surgical programmes, depending on performance size of the participating departments. d Attributed relevance of individual factors on restriction of capacities. e Need to triage surgical procedures. f Estimated degree of impact of individual factors on triage. OR, operating room. c, P = 0⋅008.

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The tumor microenvironment plays an important role in the tumor biology. Overall survival of tumor patients after resection is influenced by tumor-infiltrating lymphocytes (TILs) as a component of the tumor stroma. However, it is not clear how to assess TILs in the tumor stroma due to heterogeneous methods in different cancer types. Therefore, we present a novel Quantification of the Tumor immune Stroma (QTiS) Algorithm to reliably and accurately quantify cells in the tumor stroma. Immunohistochemical staining of CD3 and CD8 cells in sections of metastatic colorectal cancer (mCRC), ovarian cancer (OvCa), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC), alltogether N = 80, was performed. Hot spots of infiltrating immune cells are reported in the literature. Reliability of the hot spot identification of TILs was examined by two blinded observers. Accuracy was tested in 1 and 3 hot spots using computed counting methods (ZEN 2 software counting (ZC), ImageJ software with subjective threshold (ISC) and ImageJ with color deconvolution (IAC)) and compared to manual counting. All tumor types investigated showed an accumulation of TILs in the tumor stroma (peri- and intratumoral). Reliability between observers indicated a high level consistency. Accuracy for CD8+/CD3+ ratio and absolute cell count required 1 and 3 hot spots, respectively. ISC was found to be the best for paraffin sections, whereas IAC was ideal for frozen sections. ImageJ software is cost-effective and yielded the best results. In conclusion, an algorithm for quantification of tumoral stroma could be established. With this QTiS Algorithm counting of tumor stromal cells is reliable, accurate, and cost-effective.