Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms.

Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.

Efficacy of local anaesthetic infiltration via wound catheters after open hepatic surgery: a systematic review and meta-analysis.

BACKGROUND: This study analysed whether local anaesthetic wound catheter infiltration (LA-WCI) as an adjunct to intravenous patient-controlled analgesia (IV-PCA) provides superior outcomes compared to IV-PCA alone following liver resection. METHODS: A systematic review and meta-analysis was conducted for randomised control trials (RCTs) comparing LA-WCI with IV-PCA(LA-WCI group) versus IV-PCA alone (IV-PCA group). PubMed and the Cochrane Library were searched for relevant articles. RESULTS: Six RCTs with a total of 440 patients were included. Opioid use in the initial 48 h was less in the LA-WCI group [MD -21.27 mg (-39.39,-3.15), p = 0.02]. Pain scores were lower in the LA-WCI group at rest at POD0 (post-operative day 0)6-8 h (p = 0.0009), POD1AM(p = 0.01), POD1PM(p = 0.02) and POD2 (p = 0.0006), and exertion at POD0 0-2 h (p = 0.05), POD1AM(p = 0.03), POD1PM(p = 0.03), POD2 (p = 0.03) and POD3 (p = 0.01). LA-WCI group had reduced length of hospital stay [MD -1.32 days (-2.23,-0.40),p = 0.005], time to ambulation [MD -5.94 h (-8.47,-3.42),p = 0.00001] and incidence of nausea and vomiting (PONV) [OR 0.17 (0.07,0.43),p = 0.0002]. No differences were observed in length of intensive care unit (ICU) stay or incidence of surgical site infections. DISCUSSION: LA-WCI as an adjunct to opiate IV-PCA post-hepatectomy reduces opioid use, pain scores at multiple time points at rest and exertion, length of hospital stay, time to ambulation and PONV. However, LA-WCI use does not alter length of ICU stay or incidence of wound infection.

Clinical outcomes of non-operative management and clinical observation in non-angioembolised hepatic trauma: A systematic review of the literature.

PURPOSE: Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE. METHODS: A systematic literature review searched "liver trauma", "hepatic trauma", "conservative management", "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test. RESULTS: A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%. CONCLUSION: NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.

The Impact of COVID-19 on Kidney Transplant Recipients in Pre-Vaccination and Delta Strain Era: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review.

BACKGROUND: The T-cell costimulation blocking agent belatacept has been identified as a possible substitute for calcineurin inhibitors, however, no consensus has been established against its use over the standard care agent Tacrolimus. AIM: To evaluate the effectiveness of belatacept based maintenance immuno-suppressive regimens in comparison to tacrolimus in renal transplantion. METHODS: We did extensive search of all the available literature comparing the role of belatacept to tacrolimus in renal transplant recipients by searching the PubMed, Embase, Cochrane, Crossref, Scopus, clinical trials registry on October 5, 2020. RESULTS: The literature search identified four randomized controlled trials (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). However, incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05). CONCLUSION: The evidence reviewed in this meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus; however, observed significantly reduced new onset diabetes mellitus after transplantation incidence and lower serum low density lipid profile levels in belatacept group. In addition, the adaptation of belatacept in renal transplantation has been forestalled by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity.

COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis.

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.

Prophylactic intra-abdominal drainage following colorectal anastomoses. A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinically evident Anastomotic Leakage (AL) remains one of the most feared complications after colorectal resections with primary anastomosis. The primary aim of this systematic review and meta-analysis was to determine whether Prophylactic Drainage (PD) after colorectal anastomoses confers any advantage in the prevention and management of AL. METHODS: Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized studies comparing clinical outcomes of patients with Drained (D) or Undrained (UD) colorectal anastomoses performed for any cause. RESULTS: Four randomized controlled trials comparing D and UD patients undergoing colorectal resections with primary anastomosis were included for quantitative synthesis. In total, 1120 patients were allocated to group D (n = 566) or group UD (n = 554). The clinical AL rate was 8.5% in the D group and 7.6% in the UD group, with no statistically significant difference (P = 0.57). Rates of radiological AL (D: 4.2% versus UD: 5.6%; P = 0.42), mortality (D: 3.6% versus UD: 4.4%; P = 0.63), overall morbidity (D: 16.6% versus UD: 18.6%, P = 0.38), wound infection (D: 5.4% versus UD: 5.3%, P = 0.95), pelvic sepsis (D: 9.7% versus UD: 10.5%, P = 0.75), postoperative bowel obstruction (D: 9.9% versus UD: 6.9%, P = 0.07), and reintervention for abdominal complication (D: 9.1% versus UD: 7.9%, P = 0.48) were equivalent between the two groups. CONCLUSIONS: The present meta-analysis of randomized controlled trials investigating the value of PD following colorectal anastomoses does not support the routine use of prophylactic drains.

Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile.

Non-alcoholic fatty liver disease (NAFLD) culminates in insulin resistance and metabolic syndrome. Because there are no approved pharmacological treatment agents for non-alcoholic steatohepatitis (NASH) and NAFLD, different signaling pathways are under investigation for drug development with the focus on metabolic pathways. Hepatocyte nuclear factor 4-alpha (HNF4A) is at the center of a complex transcriptional network where its disruption is directly linked to glucose and lipid metabolism. Resetting HNF4A expression in NAFLD is therefore crucial for re-establishing normal liver function. Here, small activating RNA (saRNA) specific for upregulating HNF4A was injected into rats fed a high-fat diet for 16 weeks. Intravenous delivery was carried out using 5-(G5)-triethanolamine-core polyamidoamine (PAMAM) dendrimers. We observed a significant reduction in liver triglyceride, increased high-density lipoprotein/low-density lipoprotein (HDL/LDL) ratio, and decreased white adipose tissue/body weight ratio, all parameters to suggest that HNF4A-saRNA treatment induced a favorable metabolic profile. Proteomic analysis showed significant regulation of genes involved in sphingolipid metabolism, fatty acid ß-oxidation, ketogenesis, detoxification of reactive oxygen species, and lipid transport. We demonstrate that HNF4A activation by oligonucleotide therapy may represent a novel single agent for the treatment of NAFLD and insulin resistance.

Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death.

AIM: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. METHODS: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. RESULTS: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). CONCLUSIONS: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.

A Systematic Review and Meta-Analysis Comparing Liver Resection with the Rf-Based Device Habib™-4X with the Clamp-Crush Technique.

Liver cancer is the sixth most common cancer and third most common cause of cancer-related mortality. Presently, indications for liver resections for liver cancers are widening, but the response is varied owing to the multitude of factors including excess intraoperative bleeding, increased blood transfusion requirement, post-hepatectomy liver failure and morbidity. The advent of the radiofrequency energy-based bipolar device Habib™-4X has made bloodless hepatic resection possible. The radiofrequency-generated coagulative necrosis on normal liver parenchyma provides a firm underpinning for the bloodless liver resection. This meta-analysis was undertaken to analyse the available data on the clinical effectiveness or outcomes of liver resection with Habib™-4X in comparison to the clamp-crush technique. The RF-assisted device Habib™-4X is considered a safe and feasible modality for liver resection compared to the clamp-crush technique owing to the multitude of benefits and mounting clinical evidence supporting its role as a superior liver resection device. The most intriguing advantage of the RF-device is its ability to induce systemic and local immunomodulatory changes that further expand the boundaries of survival outcomes following liver resection.

The use of radiofrequency ablation in pancreatic cancer in the midst of the dawn of immuno-oncology.

Despite significant improvement in treatment, the prognosis of pancreatic ductal adenocarcinoma remains poor as the biology of the tumour affects survival even when a radical resection has been performed. Pancreatic cancer remains resistant to currently available chemotherapeutic options. Recently, immunotherapy has achieved significant results in certain types of cancer. However, for pancreatic cancer, results were not initially encouraging as pancreatic cancer microenvironment is highly immunosuppressive. Radiofrequency ablation is currently used as treatment option especially for liver cancer with significant results. However, in pancreatic cancer, the use of radiofrequency ablation is relatively new. Radiofrequency ablation has been identified as a promising mechanism to induce antigen-presenting cell infiltration and enhance systemic antitumour T-cell immune response and tumour regression. In this short communication, we briefly review the role of radiofrequency ablation in pancreatic cancer and explore the idea that the combination of radiofrequency ablation with immunotherapy could represent a novel and promising treatment.

Radiofrequency-assisted liver resection: Technique and results.

BACKGROUND: Radiofrequency (RF)-assisted liver resection allows non-anatomical liver resection with reduced blood loss and offers the opportunity for a combination of resection and ablation. However, there are still concerns with regard to postoperative complications related to this technique. In the present study, we discuss the technical aspects of RF-assisted liver resections and analyse the rate of perioperative complications, focusing on post-hepatectomy liver failure (PLF), bile leak and abscess, and mortality. METHODS: Between 2001 and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver resections for benign and malignant liver tumours were reviewed retrospectively to assess perioperative outcomes. RESULTS: Median intraoperative blood loss was 130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal collections requiring percutaneous drainage developed in 8.7% of all patients, while bile leak at resection margin developed in 2.8% of the cases. Major liver resection was performed in 34% of patients and the incidence of PLF was 1.5% with one directly related mortality (0.1%). CONCLUSION: RF-assisted liver resection has evolved into a feasible and safe technique of liver resection with an acceptable incidence of perioperative morbidity and a low incidence of PLF and related mortality.

Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer.

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes. Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate. Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.

Normothermic ex-vivo liver perfusion: where do we stand and where to reach?

INTRODUCTION: Nowadays liver transplantation is considered as the treatment of choice, however, the scarcity of suitable donor organs limits the delivery of care to the end-stage liver disease patients leading to the death while on the waiting list. The advent of ex-situ normothermic machine perfusion (NMP) has emerged as an alternative to the standard organ preservation technique, static cold storage (SCS). The newer technique promises to not only restore the normal metabolic activity but also attempt to recondition the marginal livers back to the pristine state, which are otherwise more susceptible to ischemic injury and foster the poor post-transplant outcomes. Areas covered: An extensive search of all the published literature describing the role of NMP based device in liver transplantation as an alternative to SCS was made on MEDLINE, EMBASE, Cochrane, BIOSIS, Crossref, Scopus databases and clinical trial registry on 10 May 2018. Expert commentary: The main tenet of NMP is the establishment of the physiological milieu, which permits aerobic metabolism to continue through out the period of preservation and limits the effects of ischemia-reperfusion (I/R) injury. In addition, by assessing the various metabolic and synthetic parameters the viability and suitability of donor livers for transplantation can be determined. This important technological advancement has scored satisfactorily on the safety and efficacy parameters in preliminary clinical studies. The present review suggests that NMP can offer the opportunity to assess and safely utilize the marginal donor livers if deemed appropriate for the transplantation. However, ongoing trials will determine its full potential and further adoption.

The Role of Normothermic Perfusion in Liver Transplantation (TRaNsIT Study): A Systematic Review of Preliminary Studies.

INTRODUCTION: The success of liver transplantation has been limited by the unavailability of suitable donor livers. The current organ preservation technique, i.e., static cold storage (SCS), is not suitable for marginal organs. Alternatively, normothermic machine perfusion (NMP) promises to recreate the physiological environment and hence holds promise for the better organ preservation. The objective of this systematic review is to provide an overview of the safety, benefits, and insight into the other potential useful parameters of NMP in the liver preservation. MATERIAL AND METHODS: We searched the current literature following registration in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42018086034 for prospective trials comparing the role of NMP device to SCS in liver transplant by searching the PubMed, EMBASE, Cochrane, BIOSIS, Crossref, and Scopus databases and clinical trial registry. RESULTS: The literature search identified five prospective clinical trials (four being early phase single institutional and single randomized multi-institutional) comparing 187 donor livers on NMP device to 273 donor livers on SCS. The primary outcome of interest was to assess the safety and graft survival at day 30 after transplant following NMP of the donor liver. Secondary outcomes included were early allograft dysfunction (EAD) in the first seven days; serum measures of liver functions as bilirubin, aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), and international normalized ratio (INR) on days 1-7; major complications as defined by a Clavien-Dindo score ≥ 3; and patient and graft survival and biliary complications at six months. The peaked median AST level between days 1 and 7 in the five trials was 417-1252 U/L (range 84-15009 U/L) while on NMP and 839-1474 U/L (range 153-8786 U/L) in SCS group. The median bilirubin level on day 7 ranged within 25-79 µmol/L (range 8-344 µmol/l) and 30-47.53 µmol/l (range 9-340 µmol/l) in NMP and SCS groups, respectively. A single case of PNF was reported in NMP group in the randomized trial while none of the other preliminary studies reported any in either group. There was intertrial variability in EAD which ranged within 15-56% in NMP group while being within 23-37% in SCS group. Biliary complications observed in NMP group ranged from 0 to 20%. Single device malfunction was reported in randomized controlled trial leading to renouncement of transplant while none of the other trials reported any machine failure, although two user related device errors inadvertent were reported. CONCLUSION: This review outlines that NMP not only demonstrated safety and efficacy but also provided the favourable environment of organ preservation, repair, and viability assessment to donor liver prior to the transplantation with low rate of posttransplantation complication as PNF, EAD, and biliary complication; however further studies are needed to broaden our horizon.

Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma.

BACKGROUND: Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. RESULTS: There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. CONCLUSION: Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. METHOD: Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.

Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer.

Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis and clinical decompensation. Around 5% of cirrhotic liver diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options and negative survival outcomes. CEPBA is a master regulator of hepatic function where its expression is known to be suppressed in many forms of liver disease including HCC. Injection of MTL-CEBPA, a small activating RNA oligonucleotide therapy (CEBPA-51) formulated in liposomal nanoparticles (NOV340- SMARTICLES) upregulates hepatic CEBPA expression. Here we show how MTL-CEBPA therapy promotes disease reversal in rodent models of cirrhosis, fibrosis, hepatosteatosis, and significantly reduces tumor burden in cirrhotic HCC. Restoration of liver function markers were observed in a carbon-tetrachloride-induced rat model of fibrosis following 2 weeks of MTL-CEBPA therapy. At 14 weeks, animals showed reduction in ascites and enhanced survival rates. MTL-CEBPA reversed changes associated with hepatosteatosis in non-alcoholic methionine and cholic-deficient diet-induced steaotic liver disease. In diethylnitrosamine induced cirrhotic HCC rats, MTL-CEBPA treatment led to a significant reduction in tumor burden. The data included here and the rapid adoption of MTL-CEBPA into a Phase 1 study may lead to new therapeutic oligonucleotides for undruggable diseases.

Role of crossmatch testing when Luminex-SAB is negative in renal transplantation.

The human leukocyte antigen (HLA) system plays an important role in the acceptance of renal graft. Long and better graft survival has been reported in patients with HLA-identical siblings and a nonreactive cytotoxicity assay (CDC). New methods of HLA-typing and anti-HLA antibody detection techniques such as flow cytometry, solid-phase immunoassays, or antigen bead assays have further improved the outcomes of renal transplant recipients. In the present review, the explicit details of these methodologies are discussed in detail.