Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma.

BACKGROUND: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. METHODS: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. RESULTS: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. CONCLUSIONS: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.

Robotic colectomy with CME versus laparoscopic colon resection with or without CME for colon cancer: a systematic review and meta-analysis.

INTRODUCTION: This systematic review with meta-analysis aimed to compare the robotic complete mesocolon excision (RCME) to laparoscopic colectomy (LC) with (LCME) or without CME (LC non-CME) in postoperative outcomes, harvested lymph nodes and disease-free survival. METHODS: We performed a systematic review with meta-analysis according to PRISMA 2020 and AMSTAR 2 guidelines. RESULTS: The literature search yielded seven comparative studies including 677 patients: 269 patients in the RCME group and 408 in the LC group. The pooled analysis concluded to a lower conversion rate in the RCME group (OR=0.17; 95% CI [0.04, 0.74], p=0.02). There was no difference between the two groups in terms of morbidity (OR=1.03; 95% CI [0.70, 1.53], p=0.87), anastomosis leakage (OR=0.83; 95% CI [0.18, 3.72], p=0.81), bleeding (OR=1.90; 95% CI [0.64, 5.58], p=0.25), wound infection (OR=1.37; 95% CI [0.51, 3.68], p=0.53), operative time (mean difference (MD)=36.32; 95% CI [-24.30, 96.93], p=0.24), hospital stay (MD=-0.94; 95% CI [-2.03, 0.15], p=0.09) and disease-free survival (OR=1.29; 95% CI [0.71, 2.35], p=0.41). In the subgroup analysis, the operative time was significantly shorter in the LCME group than RCME group (MD=50.93; 95% CI [40.05, 61.81], p<0.01) and we noticed a greater number of harvested lymph nodes in the RCME group compared with LC non-CME group (MD=8.96; 95% CI [5.98, 11.93], p<0.01). CONCLUSIONS: The robotic approach for CME ensures a lower conversion rate than the LC. RCME had a longer operative time than the LCME subgroup and a higher number of harvested lymph nodes than the LC non-CME group.

Association of pre- and early post-transplant serum amino acids and metabolites of amino acids and liver transplant outcome.

The aim of the present study was to investigate association of serum amino (AA) acids and metabolites of AAs with post-transplant outcome in liver transplant recipients. Eighty-nine patients with end-stage liver diseases and available pre- and early post-transplant serum were characterised as patients with (GI) and without one-year mortality (GII) and patients with and without early graft dysfunction (EAD). A panel of pre- and early post-transplant serum levels of AAs and early and metabolites of tryptophan were measured using tandem mass spectrometry. Patient groups had significantly higher pre-transplant serum levels of phenylalanine, tryptophan, and tryptophan metabolites than healthy controls (for all p<0.001). Pre-transplant serum levels of all these parameters were significantly higher in GI than in GII (for all p<0.001). GI had a higher MELD score and re-transplantation number than GII (p≤0.005 for both investigations). Serum bilirubin on day 5 and serum phenylalanine on day 10 post-transplant were associated parameters of mortality, whereas day 1post-transplant phenylalanine and kynurenine and female gender were associated parameters of EAD. Our results indicate that pre- and early post-transplant levels of phenylalanine, tryptophan and metabolites of tryptophan are increased in patients and are associated with EAD and one-year mortality in liver transplant recipients.

Analysis of the biliostatic potential of two sealants in a standardized porcine model of liver resection.

BACKGROUND: Improved resection techniques has decreased mortality rate following liver resections(LRx). Sealants are known as effective adjuncts for haemostasis after LRx. We compared biliostatic effectiveness of two sealants in a standardized porcine model of LRx. MATERIAL AND METHODS: We accomplished left hemihepatectomy on 27 pigs. The animals were randomized in control group(n = 9) with no sealant and treatment groups (each n = 9), in which resection surfaces were covered with TachoSil® and TissuFleece®/Tissucol Duo®. After 5 days the volume of ascites(ml), bilioma and/or bile leakages and degree of intra-abdominal adhesions were analysed. RESULTS: Proportion of ascites was lower in TissuFleece/Tissucol Duo® group. The ascites volume was lower in TachoSil® group. In sealant groups, increased adhesion specially in the TachoSil® group was seen. A reduction of the "bilioma rate" was seen in sealant groups, which was significantly lower in TissuFleece®/Tissucol Duo® group. CONCLUSION: In a standardized condition sealants have a good biliostatic effect but with heterogeneous potentials. This property in combination with the cost-benefit analysis should be the focus of future prospective studies.

Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

AIMS: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies. RESULTS: After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death. CONCLUSIONS: Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately.

Treatment-associated Fatigue in Cancer Patients Treated with Immune Checkpoint Inhibitors; a Systematic Review and Meta-analysis.

AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies. RESULTS: In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001). CONCLUSIONS: The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.

The role of an interdisciplinary transplant team on living donation kidney transplantation program.

During the last decades, the disparity between the organ supply and the demand for kidney transplantation in Europe has led to consider living donors as a more acceptable option. In the last 7 years, we have established an interdisciplinary supporting transplant team to increase the rate of living donation. After 2001, the new interdisciplinary transplant team consisted of a transplant surgeon, a nephrologist, a pediatrician, a radiologist, a psychologist, a transplant coordinator, and a transplant nurse. We performed a prospective analysis to examine the effect of implementing this team on our living donation program. Demographic data, the annual number of procedures, the duration of waiting, and the cold ischemia time were evaluated among brain-dead and living donors. From January 2002 until December 2008, the number of patients who were annually on the waiting list increased 42% (from 377 to 536 patients). Consequently, the number of the total kidney transplants increased from 81 to 120 with an annual median of 98 cases. By implementing the interdisciplinary transplant team, a significant increase of living kidney donors was observed: from 18 to 42 cases; median = 27). In the last 7 years, a total number of 796 kidney transplants have been performed: 567 from brain-dead and 229 from living donors. In 2001, the waiting list times for recipients who received grafts from brain-dead versus living donors were 1356 versus 615 days respectively. Compared with 2008, the duration on the waiting list decreased significantly for patients receiving a living donor graft, whereas there was a slight increase for the patients in the brain-dead group: brain death versus living donors: 1407 versus 305 days. The interdisciplinary approach has also reduced the cold ischemia time for the living donor recipients: 3 hours and 42 minutes in 2001 versus 2 hours and 50 minutes in 2008. During the last years, by implementing an interdisciplinary transplant team, supporting living donor procedures has produce a gradual increase in the number of kidney transplants from living donors with a remarkable decrease in waiting and cold ischemia times, the latter presumably influencing graft quality.