Prognostic value of the neutrophil-to-lymphocyte ratio in advanced hepatocellular carcinoma: An exploratory analysis from the ARQ197-215 study

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Long-term outcome of liver transplantation for unresectable liver metastases from neuroendocrine neoplasms: a Belgian retrospective multi-centre study

peer reviewedBackground: Liver transplantation (LT) is the only curative treatment for unresectable liver metastases from neuroendocrine neoplasms (NEN-Liver-Mets). While recurrence is frequent after LT, there is limited data available in the literature on the outcome of recurrent patients. Methods: We retrospectively reviewed the medical records of all patients who underwent LT by NEN-Mets at the six LT centres in Belgium from 1986 to 2020. Patient and tumour characteristics, indication for transplantation, overall survival (OS), disease-free survival (DFS), and tumour recurrence and outcomes were analysed. Results: Forty patients underwent a LT for NEN-Liver-Mets in Belgium. Twenty-nine patients were male (74.2%) with a mean age of 41.9 and 47.1 years at the time of NEN diagnosis and LT, respectively. WHO classification was available for 32 patients and changed over time (see table below). OS post-LT at 1-, 5-, and 10-years are: 84,3%, 65,0% and 54,6% respectively, while the overall DFS are: 76.3%, 44.5% and 38.2% in the same intervals. Patients transplanted after 2010 showed better OS at 5-and 10-years (74.8% and 74.8%) when compared with patients transplanted before (60,0% and 49.5%). Twenty patients (50%) presented a NEN recurrence, of this, 14 (70%) were transplanted before 2010 and only 6 (30%) were transplanted afterwards (p=0.03). The median time for recurrence diagnosis was 12.3 months (range: 5.1 to 69.2). The most frequent recurrence treatments were surgical resection, somatostatin analogs, chemotherapy, and sunitinib therapy (8, 6, 6, and 4 patients, respectively). Survival rates were 89.5% and 56.1% at 1- and 5-years after recurrence diagnosis.Conclusions: Patients transplanted for unresectable NEN-Liver metastases had good long-term survival. Although the total recurrence rate is high, it decreased dramatically after 2010, probably due to better patient selection. Furthermore, recurrence treatment should be recommended as it may prolong patient survival

A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush <it>Lindera obtusiloba </it>(<it>L.obtusiloba</it>) is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of <it>L.obtusiloba </it>extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of <it>L.obtusiloba </it>extract on human hepatocellular carcinoma (HCC) cell lines and the signaling pathways involved.</p> <p>Methods</p> <p>Four human HCC cell lines representing diverse stages of differentiation were treated with <it>L.obtusiloba </it>extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined.</p> <p>Results</p> <p><it>L.obtusiloba </it>extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, <it>L.obtusiloba </it>extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase.</p> <p>Conclusions</p> <p>The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized <it>L.obtusiloba </it>extract should be further analysed for its active compounds and explored as (complementary) treatment option for HCC.</p

Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study

To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n=56) (experimental treatment group) or TMX alone (n=53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4–4.6) for the experimental treatment group and 6 months (CI 95% 2–10) for the control group (P=0.609). There was no difference in terms of α-foetoprotein (α-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, α-FP level <400 ng ml−1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC

Novel Gemcitabine Conjugated Albumin Nanoparticles: a Potential Strategy to Enhance Drug Efficacy in Pancreatic Cancer Treatment

Purpose: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. Methods: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis. Further, BSA nanoparticles were developed from BSA-GEM conjugate and extensively evaluated against in-vitro pancreatic cancer cell lines to explore cellular uptake pathways and therapeutic efficacy. Results: Various characterization techniques confirmed covalent conjugation of GEM with BSA. GEM-BSA conjugate was then transformed into NPs via high pressure homogenization technique with particle size 147.2 ± 7.3, PDI 0.16 ± 0.06 and ZP -19.2 ± 1.4. The morphological analysis by SEM and AFM revealed the formation of smooth surface spherical nanoparticles. Cellular uptake studies in MIA PaCa-2 (GEM sensitive) and PANC-1 (GEM resistant) pancreatic cell lines confirmed energy dependent clathrin internalization/endocytosis as a primary mechanism of NPs uptake. In-vitro cytotoxicity studies confirmed the hNTs independent transport of GEM in MIA PaCa-2 and PANC-1 cells. Moreover, DNA damage and annexin-V assay revealed significantly higher apoptosis level in case of cells treated with GEM-BSA NPs as compared to free GEM. Conclusions: GEM-BSA NPs were found to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM and thus demonstrated promising therapeutic potential over free drug

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Endoscopic ultrasound of the bile ducts and the pancreas. Biennial review of literature 2003-2004

Ces deux dernières années ont été prolifiques dans le domaine de l’écho-endoscopie bilio-pancréatique avec la publication d’environ 200 articles. A la lecture, cinq grands thèmes ont été plus particulièrement abordés : 1) la mise au point des sténoses biliaires indéterminées ; 2) le diagnostic et la mise au point des tumeurs pancréatiques ; 3) l’amélioration et la mise au point de nouvelles techniques de prélèvements ; 4) l’impact de l’écho-endoscopie sur la réalisation d’autres examens (cholangio-wirsungographie rétrograde, IRM... ), dans la mise au point des pathologies bilio-pancréatiques. Enfin, les développements de techniques thérapeutiques sont analysés dans quelques publications

How and why do I explore the mediastinum ?

L'échoendoscopie (EE) a été initialement développée pour le bilan d'extension des cancers gastro-intestinaux. Elle fournit également un excellent accès au médiastin à travers la paroi oesophagienne. Les masses médiastinales représentent un challenge diagnostique du fait de leur proximité par rapport à d'importantes structures vasculaires et pulmonaires, de la difficulté d'accès pour les prélèvements tissulaires et du fait d'un grand nombre de pathologies potentielles. L'EE a été démontrée supérieure à la tomodensitométrie dans l'évaluation des ganglions métastatiques, dans la différenciation de la nature bénigne ou maligne des ganglions et dans la caractérisation des lésions kystiques. L'EE permet en outre un diagnostic cytologique par aspiration à l'aiguille fine avec une haute sensibilité et spécificité. La technique de l'imagerie par EE du médiastin sera décrite de même que les indications et les limitations de la ponction guidée sous EE

Severe symptomatic hypomagnesaemia induced by the chronic use of proton pump inhibitors: a case report of a patient with Zollinger-Ellison syndrome.

The association between proton pump inhibitor (PPI) therapy and hypomagnesaemia has been recognized since 2006. We report the case of a 51-year-old woman who developed severe symptomatic hypomagnesaemia after a long-term PPI therapy given for recurrent peptic ulcer disease. Hypomagnesaemia could only partially be resolved during substitution therapy, but was corrected after withdrawal of the PPI. Recurrence of hypomagnesaemia occurred after retreatment with PPIs, supporting the causal relationship. An underlying gastric acid hypersecretion (Zollinger-Ellison syndrome) was highly suspected and eventually controlled by a combination of a histamine 2-receptor antagonist and octreotide, without the need for further PPI therapy after 2 years of follow-up