Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

Management of borderline and locally advanced pancreatic cancer:Where do we stand?

Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation- equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on Pub Med and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia- the loss of muscle mass- is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the preoperative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and longterm outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepatopancreatico-biliary resections.

Surgery for colorectal liver metastases: The evolution of determining prognosis

Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative fac- tors, these have been inconsistent in accurately deter- mining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcrip- tase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predict- ing survival after surgical resection have been sup- ported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver metastasis.We herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergo-ing resection with curative intent.

Early diagnosis and therapeutic strategies for hepatocellular carcinoma:From bench to bedside

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths worldwide.The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments.Despite being widely used,alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC.The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins,metabolites,circulating tumor deoxyribonucleic acid,and circulating non-coding ribonucleic acid.Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment,thus prolonging survival outcomes.Currently,multiple clinical trials involving locoregional,systemic therapies,and combinations of these modalities are changing therapeutic strategies for different stage HCC.Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future.This review summarizes the most recent advances in noninvasive early molecular detection,current therapy strategies,and potential immunotherapeutic innovations of HCC.

Liver resection versus liver transplantation for hepatocellular carcinoma within the Milan criteria based on estimated microvascular invasion risks

Background:Preoperative prediction of microvascular invasion(MVI)in hepatocellular carcinoma(HCC)may optimize individualized treatment decision-making.This study aimed to investigate the prognostic differences between HCC patients undergoing liver resection(LR)and liver transplantation(LT)based on predicted MVI risks.Methods:We analysed 905 patients who underwent LR,including 524 who underwent anatomical resection(AR)and 117 who underwent LT for HCC within the Milan criteria using propensity score matching.A nomogram model was used to predict preoperative MVI risk.Results:The concordance indices of the nomogram for predicting MVI were 0.809 and 0.838 in patients undergoing LR and LT,respectively.Based on an optimal cut-off value of 200 points,the nomogram defined patients as high-or low-risk MVI groups.LT resulted in a lower 5-year recurrence rate and higher 5-year overall survival(OS)rate than LR among the high-risk patients(23.6%vs 73.2%,P<0.001;87.8%vs 48.1%,P<0.001)and low-risk patients(19.0%vs 45.7%,P<0.001;86.5%vs 70.0%,P=0.002).The hazard ratios(HRs)of LT vs LR for recurrence and OS were 0.18(95%confidence interval[CI],0.09–0.37)and 0.12(95%CI,0.04–0.37)among the high-risk patients and 0.37(95%CI,0.21–0.66)and 0.36(95%CI,0.17–0.78)among the low-risk patients.LT also provided a lower 5-year recurrence rate and higher 5-year OS rate than AR among the high-risk patients(24.8%vs 63.5%,P=0.001;86.7%vs 65.7%,P=0.004),with HRs of LT vs AR for recurrence and OS being 0.24(95%CI,0.11–0.53)and 0.17(95%CI,0.06–0.52),respectively.The 5-year recurrence and OS rates between patients undergoing LT and AR were not significantly different in the low-risk patients(19.4%vs 28.3%,P=0.129;85.7%vs 77.8%,P=0.161).Conclusions:LT was superior to LR for patients with HCC within the Milan criteria with a predicted high or low risk of MVI.No significant differences in prognosis were found between LT and AR in patients with a low risk of MVI.