HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation. Potential implications beyond tolerance

Background: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis. Methods: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(-1082G > A,-819 T > C,-592A > C), transforming growth factor-β(+ 869 T > C,+915C > G), IL-6(-174G > C), tumor necrosis factor-α(-308G > A) and IL-18(-137G > C,-607C > A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed. Results: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors. Conclusions: The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation

Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation From Maastricht Category-III Donors After Circulatory Death

Background. Standard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use. Methods. In this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor = 60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor >= 60 years, 40 recipients). Results. After 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m(2) vs 45.0, 33.0-58.0 mL/min per 1.73 m(2); P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73m(2) vs 41, 40.0-42.0 mL/min per 1.73m(2); P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti-IL2-receptor-alpha monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss. Conclusions. Overall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation

Global management of a common, underrated surgical task during the COVID-19 pandemic. Gallstone disease. An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion: In the ongoing COVID-19 emergency, the surgical treatment of GD is postponed, resulting in a huge number of untreated patients who could develop severe morbidity. Updated guidelines and dedicated pathways for patients with benign disease awaiting elective surgery are mandatory to prevent further aggravation of the overloaded healthcare systems

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate "high-" and "low-benefit" patients. To do so, the innovative concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (MELD, alpha-fetoprotein, Milan-Criteria status and radiological response) displayed a high effect in terms of delta-benefit. According to these risk factors, four benefit groups were identified. Patients with three-four factors ("no-benefit group", n=405/2103; 19·2%) had no benefit of LT compared to alternative treatments. Inversely, patients without any risk factor ("large-benefit group", n=108; 5·1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The here presented innovative ITT transplant survival benefit allows to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equal way for organ allocation. Patients with no benefit should be de-listed, whilst patients with large benefit ratio should be prioritized for LT. This article is protected by copyright. All rights reserved

Global management of a common, underrated surgical task during the COVID-19 pandemic: Gallstone disease - An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion

Гепатоцеллюлярный рак и трансплантация печени: от хаоса к порядку

The care for liver-diseased patients presenting with hepatocellular cancer (HCC) is changing rapidly. Many treatment possibilities and caregivers belonging to a multitude of specialities troubled the therapeutic algorithm of the liver cancer patients. HCC in both normal and diseased livers has to be considered firstly as a surgical disease. The possibilities of surgery, including liver resections, as well as liver transplantation, have been underestimated and even been minimalized mainly as a consequence of many studies promoting in an unlimited way all different kinds of locoregional non-surgical and systemic therapies. Locoregional therapies and surgical procedures should not be seen as competing, but as complementary treatment options. Locoregional therapies are of value if surgery is not possible; in the context of transplantation they have an important role as ‘downstaging procedures’ allowing for bringing of transplantable patients into the required inclusion criteria. Systemic therapies and living donor liver transplantation will without any doubt occupy a more important role in the future therapeutic scheme of HCC.Подходы к  лечению пациентов с  гепатоцеллюлярным раком (ГЦР), развившимся на фоне заболевания печени, быстро меняются. Выбор терапевтического алгоритма осложняется также по причине множества существующих вариантов лечения и участия в процессе большого числа врачей самых разных специальностей. ГЦР независимо от этиологии следует в первую очередь рассматривать как хирургическую болезнь. Возможности хирургии, включая частичную резекцию и  трансплантацию печени, долго недооценивались и даже были сведены к  минимуму вследствие многочисленных исследований, результаты которых привели к  продвижению различных методов местно-регионарного и  системного лечения. Местно-регионарное лечение и хирургические вмешательства следует считать не конкурирующими, а  взаимодополняющими подходами к  лечению. Методы местно-регионарного лечения имеют значение только при невозможности проведения оперативного вмешательства. В контексте трансплантации они играют большую роль как способ уменьшения стадии опухоли, то есть приведения пациентов, которым может быть выполнена трансплантация, в соответствие с требуемыми критериями отбора. В будущем значимость системной терапии и трансплантации печени живого донора в лечении ГЦР, несомненно, будет повышаться