Combining F-18-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma

The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%;p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non-F-18-FDG-avid and F-18-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25;p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT

Propensity matched comparison of extrapleural pneumonectomy and pleurectomy/decortication for mesothelioma patients

OBJECTIVES: The objective of this retrospective study was to assess perioperative outcomes, overall survival and freedom from recurrence after induction chemotherapy followed by extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) in patients with mesothelioma in a propensity score matched analysis. METHODS: Between September 1999 and August 2015, 167 patients received multimodality treatment (platinum-based chemotherapy followed by EPP [n = 141] or P/D [n = 26]). We performed 2:1 propensity score matching for gender, laterality, epithelioid histological subtype and International Mesothelioma Interest Group (iMig) stage (52 EPP and 26 P/D). RESULTS: Postoperative major morbidity (48% vs 58%, P = 0.5) was similar in both groups; however, the complication profile and severity were different and favoured P/D; the 90-day mortality (8% vs 0%, P = 0.3) rate was lower in P/D although not statistically significant. Prolonged air leak (≥10 days) occurred in 15 patients (58%) undergoing P/D. The intensive care unit stay was significantly longer after EPP (P = 0.001). Freedom from recurrence was similar for both groups (EPP: median 15 months, 95% confidence interval [CI]: 10–21; P/D: 13 months, 95% CI: 11–17) (P = 0.2). Overall survival was significantly longer for patients undergoing P/D (median 32 months, 95% CI: 29–35) compared to EPP (23 months, 95% CI: 21–25) (P = 0.031), but in the P/D group many cases were censored (73%) and the follow-up time was relatively short. CONCLUSIONS: P/D and EPP seem to have similar rates of major morbidity, although the profile of complications is different and more severe after EPP. Freedom from recurrence is comparable in both groups whereas improved overall survival needs to be confirmed in a large patient group with longer follow-up

Dokaz i kvantificiranje ovčjeg herpesvirusa 2 u Hrvatskoj

Ovine herpesvirus-2 (OvHV-2), a gammaherpesvirus (genus Rhadinovirus) causes a severe disease known as sheep-associated malignant catarrhal fever (SA-MCF) in certain ruminants, such as cow, deer, bison and water buffalo. Suspected cases of SA-MCF in cows without identififi cation of the agent have been reported in Croatia in the past. In June 2005, on a farm in northwest Croatia, where 17 Simmental diary cows and 2 heifers shared stables and meadows with sheep, a 13 month-old heifer showed symptoms reminiscent of SA-MCF, including anorexia, high fever, nasal discharge, and neurological symptoms, such as ataxia, tremor, convulsions and hyperesthesia. The animal died within 14 days. Gross necropsy fifi ndings were sharply demarcated erosions on mucosal surfaces, including the tongue, oral mucosa, esophagus, abomasum, jejunum, colon, caecum and urinary bladder. Histopathology revealed extremely severe perivascular and intramural arterial infifi ltrations with mononuclear cells, mostly lymphocytes. These lesions were seen in almost every organ, especially the brain and lungs. Formaldehyde fixed samples from the brain, cerebellum, spleen and lymph nodes were obtained and subjected to DNA extraction procedures. Fluorogenic real-time PCR (Polymerase chain reaction) amplififi cation specific to OvHV-2 DNA was performed and OvHV-2 DNA was detected in the brain, cerebellum and spleen, as well as in the lymph nodes. These data indicate that the animal had been infected with OvHV-2, the agent of SA-MCF. For the first time, OvHV-2 was identified and quantified in a Croatian heifer as the causative agent of SA-MCF.Ovčji herpesvirus 2 (OvHV-2) iz roda Rhadinovirus, potporodice Gammaherpesvirinae uzročnik je zarazne korice goveda u nekih vrsta domaćih i divljih preživača. Dosad su u Republici Hrvatskoj zabilježeni mnogi slučajevi sumnje na pojavu zarazne korice u goveda temeljeni na kliničkoj metodi dijagnosticiranja, ali bez dokaza uzročnika bolesti. U lipnju 2005. godine na jednoj farmi u sjeverozapadnoj Hrvatskoj zabilježena je pojava zarazne korice goveda u jedne junice, simentalske pasmine, u dobi od 13 mjeseci, koja je bila smještena u istoj staji s još 17 mliječnih krava i jednom junicom simentalske pasmine te manjim stadom ovaca. Životinja je naglo oboljela uz znakove gubitka apetita, visoke vrućice, seroznog iscjetka iz nosa te pojavom znakova središnjega živčanoga sustava, ataksije, tremora, grčeva i hiperestezije. Životinja je uginula 14. dan od početka prvih znakova bolesti. Razudbom je utvrđena prisutnost oštro ograničenih erozija na sluznici jezika, usne šupljine, jednjaka, sirišta, tankoga, debeloga i slijepoga crijeva te mokraćnoga mjehura. Histopatološki je gotovo u svakom organu, a posebno u mozgu i plućima, utvrđena jaka perivaskularna i intramuralna infiltracija arterija mononuklearnim stanicama, većinom limfocitima. Iz formalinom fiksiranih uzoraka mozga, maloga mozga, slezene i limfnih čvorova izdvojena je DNK i podvrgnuta fluorogenoj real-time PCR amplifikaciji specifičnoj za OvHV-2. OvHV-2 dokazan je i kvantificiran u svim pretraživanim organima. Dobiveni rezultat upućuje na to da je uginula životinja bila zaražena s OvHV-2 što je ujedno i prvi dokaz uzročnika zarazne korice goveda u Hrvatskoj

Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics.

T cell migration via afferent lymphatics to draining lymph nodes (dLNs) depends on expression of CCR7 in T cells and CCL21 in the lymphatic vasculature. Once T cells have entered lymphatic capillaries, they slowly migrate into contracting collecting vessels. Here, lymph flow picks up, inducing T cell detachment and rapid transport to the dLNs. We find that the atypical chemokine receptor 4 (ACKR4), which binds and internalizes CCL19 and CCL21, is induced by lymph flow in endothelial cells lining lymphatic collectors, enabling them to scavenge these chemokines. In the absence of ACKR4, migration of T cells to dLNs in TPA-induced inflammation is significantly reduced. While entry into capillaries is not impaired, T cells accumulate in the ACKR4-deficient dermal collecting vessel segments. Overall, our findings identify an ACKR4-mediated mechanism by which lymphatic collectors facilitate the detachment of lymph-borne T cells in inflammation and their transition from crawling to free-flow toward the dLNs

Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma: A Multi-Center, Randomized, Controlled Trial (pro-duct001)

Background Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. Methods We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Results Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. Conclusions This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched

Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semiquantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OS/PFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naive and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OS/PFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis nonepithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p< 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies

Tailoring the Thermal and Mechanical Properties of PolyActiveTM Poly(Ether-Ester) Multiblock Copolymers Via Blending with CO2-Phylic Ionic Liquid

The last decade has seen an exponential increase in the number of studies focused on novel applications for ionic liquids (ILs). Blends of polymers with ILs have been proposed for use in fuel cells, batteries, gas separation membranes, packaging, etc., each requiring a set of specific physico-chemical properties. In this work, blends of four grades of the poly(ether-ester) multiblock copolymer PolyActive&trade; with different concentrations of the CO2-philic 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][Tf2N] were prepared in the form of dense films by a solution casting and solvent evaporation method, in view of their potential use as gas separation membranes for CO2 capture. Depending on the polymer structure, the material properties could be tailored over a wide range by means of the IL content. All samples were dry-feeling, highly elastic self-standing dense films. The microstructure of the blends was studied by scanning electron microscopy with a backscattering detector, able to observe anisotropy in the sample, while a special topographic analysis mode allowed the visualization of surface roughness. Samples with the longest poly(ethylene oxide terephthalate) (PEOT) blocks were significantly more anisotropic than those with shorter blocks, and this heterogeneity increased with increasing IL content. DSC analysis revealed a significant decrease in the melting enthalpy and melting temperature of the crystalline PEOT domains with increasing IL content, forming an amorphous phase with Tg &asymp; &minus;50 &deg;C, whereas the polybutylene terephthalate (PBT) phase was hardly affected. This indicates better compatibility of the IL with the polyether phase than the polyester phase. Young&rsquo;s modulus was highest and most IL-dependent for the sample with the highest PEOT content and PEOT block length, due to its high crystallinity. Similarly, the sample with short PEOT blocks and high PBT content also showed a high modulus and tensile strength, but much lower maximum elongation. This study provides a detailed discussion on the correlation between the morphological, thermal, and mechanical properties of these PolyActive&trade;/[BMIM][Tf2N] blends

Effective operating room (OR) utilization by performing low-complex surgical procedures during the 2020 corona pandemic

Purpose!#!The SARS-CoV-2 pandemic has almost stopped all elective surgical treatment throughout the world. As operating room (OR) capacities are reduced everywhere to ensure availability of intensive care capacities, especially low-complex surgical procedures are often postponed. These include totally implantable central-venous access ports which are important for the oncologic treatment of cancer patients.!##!Methods!#!In our study, we investigated the potential of an outpatient surgical centre (OSC) in terms of workflow effectiveness compared to the central operating room complex (COR) of a university hospital using low-complex surgical procedures as an example. Data of 524 consecutive patients who received a Port-a-cath procedure (422 implantations (80.5%) and 102 explantations (19.5%)) in our department between February 2019 and February 2020 were evaluated.!##!Results!#!A total of 277 patients were operated in outpatient surgical centre (OSC), and 247 patients received the procedure in the central OR (COR) complex. Grade II and III complications according to the Clavien-Dindo classification occurred in 5.2% (OSC) and 7.3% (COR) of patients. Incision-to-suture time was significantly quicker in the OSC group (36 vs. 42 min., p &amp;lt; 0.032). Total OR time (01:08 vs. 01:20 h) and preparation-to-incision time were also shorter in the OSC group (12 vs. 17 min., p &amp;lt; 0.002).!##!Conclusion!#!In order to ensure effective OR utilization especially in times of the corona pandemic, the use of smaller decentralized OR units, e.g., outpatient surgical centres, for performing low-complex surgical cases is beneficial. Our study revealed shorter total OR and preparation-to-incision times

Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma†

OBJECTIVES To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment. METHODS Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records. RESULTS The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04). CONCLUSIONS Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner

Demonstration and quantification of ovine herpesvirus 2 in Croatia- a case report

Ovine herpesvirus-2 (OvHV-2), a gammaherpesvirus (genus Rhadinovirus) ) causes a severe disease known as sheep-associated malignant catarrhal fever (SA-MCF) in certain ruminants, such as cow, deer, bison and water buffalo. Suspected cases of SA-MCF in cows without identification of the agent have been reported in Croatia in the past. In June 2005, on a farm in northwest Croatia, where 17 Simmental diary cows and 2 heifers shared stables and meadows with sheep, a 13 month-old heifer showed symptoms reminiscent of SA-MCF, including anorexia, high fever, nasal discharge, and neurological symptoms, such as ataxia, tremor, convulsions and hyperesthesia. The animal died within 14 days. Gross necropsy findings were sharply demarcated erosions on mucosal surfaces, including the tongue, oral mucosa, esophagus, abomasum, jejunum, colon, caecum and urinary bladder. Histopathology revealed extremely severe perivascular and intramural arterial infiltrations with mononuclear cells, mostly lymphocytes. These lesions were seen in almost every organ, especially the brain and lungs. Formaldehyde fixed samples from the brain, cerebellum, spleen and lymph nodes were obtained and subjected to DNA extraction procedures. Fluorogenic real-time PCR (Polymerase chain reaction) amplification specific to OvHV-2 DNA was performed and OvHV-2 DNA was detected in the brain, cerebellum and spleen, as well as in the lymph nodes. These data indicate that the animal had been infected with OvHV-2, the agent o