Antiviral prophylaxis or preemptive therapy for cytomegalovirus after liver transplantation?: A systematic review and meta-analysis.

Background: To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients. Methods: We searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: With a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05). Conclusions: We found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality.

Histological tumor micronecrosis in resected specimens after R0 hepatectomy for hepatocellular carcinomas is a factor in determining adjuvant TACE: A retrospective propensity score-matched study.

BACKGROUND: Tumor micronecrosis is a less investigated pathological feature of hepatocellular carcinoma (HCC). This study was aimed at evaluating the value of micronecrosis for guiding adjuvant transcatheter arterial chemoembolization (TACE) in HCC management. METHODS: We retrospectively reviewed the data of patients with HCC who underwent curative liver resection in our center from 2014 to 2018. The patients were divided into micronecrosis (+) and micronecrosis (-) groups. In each group, overall survival (OS) and disease-free survival (DFS) were compared between patients who underwent adjuvant TACE and those who did not. Propensity score matching (PSM) was conducted at a ratio of 1:1 to control selection bias. Univariate and multivariate analyses were performed to determine independent prognostic factors. Mass cytometry was applied to compare the immunological status of HCCs between the two groups. RESULTS: A total of 897 patients were included, with 417 and 480 patients in the micronecrosis (+) and micronecrosis (-) groups, respectively. No significant difference was detected in baseline parameters after PSM. In the micronecrosis (+) group, patients who underwent adjuvant TACE had significant longer OS than did those who did not (P = 0.004). However, patients in the micronecrosis (-) group did not benefit from adjuvant TACE. Although adjuvant TACE prolonged the DFS of patients with severe micronecrosis (P = 0.034), it may adversely affect the DFS of patients without micronecrosis (P = 0.131). Multivariate analysis showed that TACE was an independent prognostic factor for patients with micronecrosis but not for those without micronecrosis. The abundance of exhausted and regulatory T cells was significantly higher in patients with micronecrosis. CONCLUSIONS: For HCC patients with micronecrosis, adjuvant TACE after curative resection could improve the prognosis, while its survival benefits were limited in HCC patients without micronecrosis. TACE should be selectively performed in patients with micronecrosis, especially those with an Nscore = 2. The immunosuppressive status of HCC patients with micronecrosis may explain the effectiveness of adjuvant TACE in such scinario.

Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?-A Systematic Review and Meta-Analysis.

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS. Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17-31.65; p < 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85-24.22; p < 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age >60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities. Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

A Seven-Gene Signature to Predict Prognosis of Patients With Hepatocellular Carcinoma.

Purpose: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has a poor prognosis. Gene-based prognostic models have been reported to predict the overall survival of patients with HCC. Unfortunately, most of the genes used in earlier prognostic models lack prospective validation and, thus, cannot be used in clinical practice. Methods: Candidate genes were selected from GEPIA (Gene Expression Profiling Interactive Analysis), and their associations with patients' survival were confirmed by RT-PCR using cDNA tissue microarrays established from patients with HCC after radical resection. A multivariate Cox proportion model was used to calculate the coefficient of corresponding gene. The expression of seven genes of interest (MKI67, AR, PLG, DNASE1L3, PTTG1, PPP1R1A, and TTR) with two reference genes was defined to calculate a risk score which determined groups of different risks. Results: Our risk scoring efficiently classified patients (n = 129) with HCC into a low-, intermediate-, and high-risk group. The three groups showed meaningful distinction of 3-year overall survival rate, i.e., 88.9, 74.5, and 20.6% for the low-, intermediate-, and high-risk group, respectively. The prognostic prediction model of risk scores was subsequently verified using an independent prospective cohort (n = 77) and showed high accuracy. Conclusion: Our seven-gene signature model performed excellent long-term prediction power and provided crucially guiding therapy for patients who are not a candidate for surgery.

NEK2 inhibition triggers anti-pancreatic cancer immunity by targeting PD-L1.

Despite the substantial impact of post-translational modifications on programmed cell death 1 ligand 1 (PD-L1), its importance in therapeutic resistance in pancreatic cancer remains poorly defined. Here, we demonstrate that never in mitosis gene A-related kinase 2 (NEK2) phosphorylates PD-L1 to maintain its stability, causing PD-L1-targeted pancreatic cancer immunotherapy to have poor efficacy. We identify NEK2 as a prognostic factor in immunologically "hot" pancreatic cancer, involved in the onset and development of pancreatic tumors in an immune-dependent manner. NEK2 deficiency results in the suppression of PD-L1 expression and enhancement of lymphocyte infiltration. A NEK binding motif (F/LXXS/T) is identified in the glycosylation-rich region of PD-L1. NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. NEK2 inhibition thereby sensitizes PD-L1 blockade, synergically enhancing the anti-pancreatic cancer immune response. Together, the present study proposes a promising strategy for improving the effectiveness of pancreatic cancer immunotherapy.

Glucose Metabolism: The Metabolic Signature of Tumor Associated Macrophage.

Macrophages exist in most tissues of the body, where they perform various functions at the same time equilibrating with other cells to maintain immune responses in numerous diseases including cancer. Recently, emerging investigations revealed that metabolism profiles control macrophage phenotypes and functions, and in turn, polarization can trigger metabolic shifts in macrophages. Those findings implicate a special role of metabolism in tumor-associated macrophages (TAMs) because of the sophisticated microenvironment in cancer. Glucose is the major energy source of cells, especially for TAMs. However, the complicated association between TAMs and their glucose metabolism is still unclearly illustrated. Here, we review the recent advances in macrophage and glucose metabolism within the tumor microenvironment, and the significant transformations that occur in TAMs during the tumor progression. Additionally, we have also outlined the potential implications for macrophage-based therapies in cancer targeting TAMs.

Risk Factors for Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF) after Distal Pancreatectomy: A Single Center Retrospective Study.

Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the considerable contributor to major complications after pancreatectomy. The purpose of this study was to evaluate the potential risk factor contributing to CR-POPF following distal pancreatectomy (DP) and discuss the risk factors of pancreatic fistula in order to interpret the clinical importance. Methods: In this retrospective study, 263 patients who underwent DP at Ningbo Medical Center Li Huili Hospital between January 2011 and January 2020 were reviewed in accordance with relevant guidelines and regulations. Patients' demographics and clinical parameters were evaluated using univariate and multivariate analyses to identify the risk factors contributing to CR-POPF. P < 0.05 was considered statistically significant. Results: In all of the 263 patients with DP, pancreatic fistula was the most common surgical complication (19.0%). The univariate analysis of 18 factors showed that the patients with a malignant tumor, soft pancreas, and patient without ligation of the main pancreatic duct were more likely to develop pancreatic fistula. However, on multivariate analysis, the soft texture of the pancreas (OR = 2.381, 95% CI = 1.271-4.460, P=0.001) and the ligation of the main pancreatic duct (OR = 0.388, 95% CI = 0.207-0.726, P=0.002) were only an independent influencing factor for CR-POPF. Conclusions: As a conclusion, pancreatic fistula was the most common surgical complication after DP. The soft texture of the pancreas and the absence of ligation of the main pancreatic duct can increase the risk of CR-POPF.

Genomic investigation of co-targeting tumor immune microenvironment and immune checkpoints in pan-cancer immunotherapy.

Drugs that target immune checkpoints (ICPs) have become the most popular weapons in cancer immunotherapy; however, they are only beneficial for a small fraction of patients. Accumulating evidence suggests that the tumor immune microenvironment (TIME) plays a critical role in anti-cancer immunity. This study aimed to assess the potential merits and feasibility of combinational targeting ICPs and TIME in cancer immunotherapy. A total of 31 cancer type-specific datasets in TCGA were individually collected by the publicly available web servers for multiple bioinformatic analyses of ICPs and TIME factors. GEPIA was used to calculate the prognostic indexes, STRING was used to construct protein-protein interactions, cBioPortal was used for visualization and comparison of genetic alterations, and TISIDB was used to explore the correlation to tumor-infiltrating lymphocytes (TILs). Intriguingly, TIME factors were identified to have more global coverage and prognostic significance across multiple cancer types compared with ICPs, thus offering more general targetability in clinical therapy. Moreover, TIME factors showed interactive potential with ICPs, and genomic alteration of TIME factors coupled with that of ICPs, at least in pancreatic cancer. Furthermore, TIME factors were found to be significantly associated with TILs, including but not limited to pancreatic cancer. Finally, the clinical significance and translational potential of further combination therapies that incorporate both ICP inhibitors and TIME factor-targeted treatments were discussed. Together, TIME factors are promising immunotherapeutic targets, and a combination strategy of TIME factors-targeted therapies with ICP inhibitors may benefit more cancer patients in the future.

Liver Transplantation for Alcohol-Related Liver Disease (ARLD): An Update on Controversies and Considerations.

According to the recent data from the United Network for Organ Sharing database, alcohol-related liver disease (ARLD) accounts to be the most common indication of liver transplantation (LT) waiting lists in the United States among men without hepatocellular carcinoma (HCC). Severe alcoholic hepatitis (AH) is serious and the life-threatening form of ARLD and should be treated timely. However, the LT for severe AH remained to be controversial among the transplant community because of marked interests about the constrained organ supply and the hazard that the AH liver recipient will return to risky drinking. Early LT for ARLD refers for a patient with severe AH undergoing LT who are non-responder to medical treatments. These patients are generally on the existing waiting list but usually followed by 6-month duration of alcohol abstinence. However, the rule of 6-month alcohol abstinence need before the LT is ambiguous. The 6-month alcohol abstinence was consistently defended in light of the compelling fact that it would enable patients to recoup from the intense impacts of alcohol to the liver. In routine, however, the purported "6-month abstinence rule" turned into a surrogate for the forecast of future drinking by ARLD patients for the LT. Careful consideration should be given to the alcohol use disorder of craving and the hazard for recidivism after the LT. As for the current situation, there, urgently, is a specific need of standardized criteria for the evaluation of patients with severe AH for earlier LT. Moreover, further studies are required precisely to develop an accurate prediction model for posttransplant alcohol recidivism. Additionally, development of a standardized protocol for post-LT follow-up and management is further needed. We carefully outlined the published experience with the LT for ARLD in this review.

Role of Collateral Venous Circulation in Prevention of Sinistral Portal Hypertension After Superior Mesenteric-Portal Vein Confluence Resection during Pancreaticoduodenectomy: a Single-Center Experience.

BACKGROUND: The ligation of the splenic vein (SV) during pancreaticoduodenectomy (PD) may result in sinistral portal hypertension (SPH). This study aimed to identify the collateral pathways that formed postoperatively and evaluate the impact of omentum and arc of Barkow preservation in PD. METHODS: Patients who underwent PD between January 2013 and May 2018 at the Second Affiliated Hospital of Zhejiang University were enrolled in this retrospective study. PD was performed with preservation of the greater omentum and arc of Barkow. Venous collaterals, spleen size, and platelet count were evaluated before and after surgery. RESULTS: In total, 330 patients underwent PD, of whom, 43 patients who underwent superior mesenteric vein (SMV)/portal vein (PV) reconstruction and splenic vein (SV) ligation were selected. No patient developed severe gastrointestinal bleeding. Three collateral routes were identified: the left gastric route, the colic marginal route, and the first jejunal route. Seventeen patients developed splenomegaly. Twenty-three patients developed thrombocytopenia. However, none of them developed gastrointestinal bleeding or other clinical complaints. CONCLUSION: Although subclinical SPH developed after SV ligation, postoperative gastrointestinal bleeding was uncommon.

Laparoscopic Spleen-Preserving Distal Pancreatectomy (LSPDP) versus Open Spleen-Preserving Distal Pancreatectomy (OSPDP): A Comparative Study.

Objective: To compare outcomes between laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and open spleen-preserving distal pancreatectomy (OSPDP) for treatment of benign and low-grade malignant tumors of the pancreas and evaluate feasibility and safety of LSPDP. Methods: The clinical data of 53 cases of LSPDP and 44 cases of OSPDP performed between January 2008 and August 2018 were retrospectively analyzed. The clinical outcomes between the two groups were compared. Results: There was no significant difference in preoperative data between the two groups. However, the LSPDP group had statistically significant shorter operative time (145.3±55.9 versus 184.7±33.5, P=0.03) and lesser intraoperative blood loss (150.6±180.8 versus 253.5±76.2, P=0.03) than that of the OSPDP group. Moreover, the LSPDP group also had statistically significant earlier passing of first flatus (2.2±1.4 versus 3.1±1.9, P=0.01), earlier diet intake (2.3±1.8 versus 3.4±2.0, P=0.01), and shorter hospital stay (6.2±7.2 versus 8.8±9.3, 0.04) than that of the OSPDP group. However, postoperative pancreatic fistula (P=0.64) and total postoperative complications (P=0.59) were not significantly different between the groups. The rate of pancreatic fistula and total postoperative complications occurred in 62.5% and 64.5%, respectively, in LSPDP group and, similarly, 70% and 70.0%, respectively, in OSPDP group. Conclusion: This study confirms that LSPDP is safe, feasible, and superior to OSPDP in terms of operative time, intraoperative blood loss, hospital stay, and postoperative recovery. Hence, it is worth popularizing LSPDP for benign and low-grade malignant tumors of the pancreas.

ABO-Incompatible Adult Living Donor Liver Transplantation in the Era of Rituximab: A Systematic Review and Meta-Analysis.

AIM: The primary aim of this study is to compare the short- and long-term outcomes between ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) with rituximab prophylaxis and ABO-compatible (ABOc) ALDLT. BACKGROUND: The strategy of ABOi liver transplantation (LT) was originated initially to increase the donor pool and to enable liver transplantation in emergency conditions. However, ABOi ALDLT remains a controversial approach in comparison to ABOc ALDLT. METHODS: PubMed, Embase, and the Cochrane Library study search were accomplished to recognize studies comparing ABOi and ABOc ALDLT. Meta-analyses were conducted based on the evaluation of heterogeneity using a fixed-effect model and a random-effect model to assess the short- and long-term outcomes following ABOi ALDLT with rituximab prophylaxis. RESULTS: Nine studies comprising a total of 3,922 patients (ABOi = 671 and ABOc = 3,251) were identified. There was no significant difference between ABOi and ABOc groups for 1-year, 3-year, and 5-year OS and graft survival, respectively. Moreover, 1-year and 3-year OS and DFS were similar between both groups for HCC patients. However, ABOi ALDLT had higher incidences of CMV infection, AMR, overall biliary complications, and biliary stricture than ABOc ALDLT and had other comparable postoperative complications. CONCLUSION: Our meta-analysis included studies comparing ABOi and ABOc ALDLT after the introduction of rituximab in a desensitization protocol for ABOi ALDLT. The results of ABOi ALDLT were comparable with those of ABOc ALDLT. However, biliary complications, CMV infection, and AMR remain a concern in the era of rituximab.

Liver Transplantation from Voluntary Organ Donor System in China: A Comparison between DBD and DCD Liver Transplants.

BACKGROUND: In China, the cases of liver transplantation (LT) from donation after citizens' death have rose year by year since the citizen-based voluntary organ donor system was initiated in 2010. The objective of our research was to investigate the early postoperative and late long-term outcomes of LT from donation after brain death (DBD) and donation after circulatory death (DCD) according to the current organ donation system in China. METHODS: Sixty-two consecutive cases of LT from donation after citizens' death performed in our hospital between February 2012 and June 2017 were examined retrospectively for short- and long-term outcomes. These included 35 DCD LT and 27 DBD LT. RESULT: Subsequent median follow-up time of 19 months and 1- and 3-year graft survival rates were comparative between the DBD group and the DCD group (81.5% and 66.7% versus 67.1% and 59.7%; P = 0.550), as were patient survival rates (85.2% and 68.7% versus 72.2% and 63.9%; P = 0.358). The duration of ICU stay of recipients was significantly shorter in the DBD group, in comparison with that of the DCD group (1 versus 3 days, P = 0.001). Severe complication incidence (≥grade III) after transplantation was identical among the DBD and DCD groups (48.1% versus 60%, P = 0.352). There was no significant difference in postoperative mortality between the DBD and DCD groups (3 of 27 cases versus 5 of 35 cases). Twenty-one grafts (33.8%) were lost and 18 recipients (29.0%) were dead till the time of follow-up. Malignancy recurrence was the most prevalent reason for patient death (38.8%). There was no significant difference in incidence of biliary stenosis between the DBD and DCD groups (5 of 27 cases versus 6 of 35 cases, P = 0.846). CONCLUSION: Although the sample size was small to some extent, this single-center study first reported that LT from DCD donors showed similar short- and long-term outcomes with DBD donors and justified the widespread implementation of voluntary citizen-based deceased organ donation in China. However, the results should be verified with a multicenter larger study.

Dermatological Disorders following Liver Transplantation: An Update.

Patients undergoing liver transplantation (LT) are at a high risk of dermatological complications compared to the general population as a result of long-term use of immunosuppressant. However, the risk is not as high as other solid organ transplantations (SOT), particularly for skin cancer. The liver is considered as an immune privileged organ since it has a low prevalence of humoral rejection in contrast to other SOT, and thus, LT requires a minimal amount of immunosuppressants compared to other SOT recipients. However, because of the large volume of the liver, patients with LT have higher donor lymphocytes that sometimes may trigger graft-versus-host-disease, yet it is rare. On the other hand, the vast majority of the nonspecific dermatological lesions linked with cirrhosis improve after removal of diseased liver or due to the immunosuppressant used after LT. Nevertheless, dermatological infections related to bacteria, viruses, and fungus after LT are not uncommon. Additionally, the incidence of IgE-mediated food allergies develops in 12.2% of LT patients and may present as life-threatening conditions such as urticaria and/or angioedema and hypersensitivity. Moreover, skin malignancies after LT are a matter of concern. Thus, posttransplant dermatological care should be provided to all LT patients for any suspicious dermatological lesions. Our goal is to give an outline of the dermatological manifestation associated with LT for the clinicians by collecting the published data from all archived case reports.

Laparoscopic Spleen-Preserving Distal Pancreatectomy (LSPDP) with Preservation of Splenic Vessels: An Inferior-Posterior Approach.

OBJECTIVE: To summarize the operation experience of laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with preservation of splenic vessels by an inferior-posterior dissection of the pancreatic body and evaluate its feasibility. METHODS: Patients undergoing LSPDS at Ningbo Li Huili Hospital and Ningbo Li Huili Eastern Hospital from January 2014 to April 2017 were recruited in this study and were analyzed retrospectively. They were divided into two groups based on the surgical approach: the inferior-posterior approach group and the other approach group. We sought to compare outcomes of the two groups. RESULTS: The LSPDP procedure was completed successfully in 49 cases, and 48 patients had their splenic artery and vein preserved, including 26 cases in the inferior-posterior approach group and 22 cases in the other approach group. There were no significant differences between the two groups with respect to age (p = 0.18), sex (p = 0.56), preoperative diabetes (p = 1.00), ASA grading (p = 1.00), tumor size (p = 0.91), intraoperative blood loss (t = -0.01, p = 0.99), hospital stay (t = -0.02, p = 0.98), and pancreatic fistula rates (p = 1.00). Patients undergoing LSPDP by the inferior-posterior approach had a shorter operative time (t = -4.13, p < 0.001) than the other approach group. CONCLUSIONS: LSPDS by the inferior-posterior approach associated with shorter operative time is safe and feasible.

Salvage Liver Transplant versus Primary Liver Transplant for Patients with Hepatocellular Carcinoma.

The strategy of salvage liver transplantation (SLT) originated for initially resectable and transplantable hepatocellular carcinoma (HCC) to preclude upfront transplantation, with SLT in the case of recurrence. However, SLT remains a controversial approach in comparison to primary liver transplant (PLT). The aim of our study was to conduct a systemic review and meta-analysis to assess the short-term outcomes, overall survival (OS), and disease-free survival (DFS) between SLT and PLT for patients with HCC, stratifying results according to the Milan criteria and donor types. A search of PubMed, EMBASE, and the Cochrane Library was conducted to identify studies comparing SLT and PLT. A fixed effects model and a random effects model meta-analysis were conducted to assess the short-term outcomes, OS, and DFS based on the evaluation of heterogeneity. SLT had superior 1-year, 3-year, and 5-year OS and DFS compared with that of PLT. After classifying data according to donor type and Milan criteria, our meta-analysis revealed: that for deceased-donor liver transplantation (DDLT) recipients, there were no significant differences in 1-year and 3-year OS rate between the SLT group and the PLT group. However, the 5-year OS rate was superior in the SLT group compared to the PLT group. Similarly, SLT had superior 1-year, 3-year, and 5-year OS rate compared to PLT in living-donor liver transplantation (LDLT) recipients. Moreover, 1-year, 3-year, and 5-year DFS were also superior in SLT compared to PLT in both the DDLT and LDLT recipients. In patients within Milan criteria there were no statistically significant differences in 1-year, 3-year, and 5-year OS and DFS between the SLT group and the PLT group. Similarly, in patients beyond Milan criteria, both SLT and PLT showed no significant difference for 1-year, 3-year, and 5-year OS rate. Our meta-analysis included the largest number of studies comparing SLT and PLT, and SLT was found to have significantly better OS and DFS. Moreover, this meta-analysis suggests that SLT has comparable postoperative complications to that of PLT, and thus, SLT may be a better treatment strategy for recurrent HCC patients and patients with compensated liver, whenever feasible, considering the severe organ limitation and the safety of SLT. However, PLT can be referred as a treatment strategy for HCC patients with cirrhotic and decompensated liver.

Liquid biopsy in pancreatic cancer: the beginning of a new era.

With dismal survival rate pancreatic cancer remains one of the most aggressive and devastating malignancy. Predominantly, due to the absence of a dependable methodology for early identification and limited therapeutic options for advanced disease. However, it takes over 17 years to develop pancreatic cancer from initiation of mutation to metastatic cancer; therefore, if diagnosed early; it may increase overall survival dramatically, thus, providing a window of opportunity for early detection. Recently, genomic expression analysis defined 4 subtypes of pancreatic cancer based on mutated genes. Hence, we need simple and standard, minimally invasive test that can monitor those altered genes or their associated pathways in time for the success of precision medicine, and liquid biopsy seems to be one answer to all these questions. Again, liquid biopsy has an ability to pair with genomic tests. Additionally, liquid biopsy based development of circulating tumor cells derived xenografts, 3D organoids system, real-time monitoring of genetic mutations by circulating tumor DNA and exosome as the targeted drug delivery vehicle holds lots of potential for the treatment and cure of pancreatic cancer. At present, diagnosis of pancreatic cancer is frantically done on the premise of CA19-9 and radiological features only, which doesn't give a picture of genetic mutations and epigenetic alteration involved. In this manner, the current diagnostic paradigm for pancreatic cancer diagnosis experiences low diagnostic accuracy. This review article discusses the current state of liquid biopsy in pancreatic cancer as diagnostic and therapeutic tools and future perspectives of research in the light of circulating tumor cells, circulating tumor DNA and exosomes.