Factors associated with failure of enhanced recovery after surgery program in patients undergoing pancreaticoduodenectomy

Background: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small propor- tion of patients fail to bene t from the ERAS program following pancreaticoduodenectomy. This study aimed to identify the risk factors associated with failure of ERAS program in pancreaticoduodenectomy. Methods: Between May 2014 and December 2017, 176 patients were managed with ERAS program fol-lowing pancreaticoduodenectomy. ERAS failure was indicated by prolonged hospital stay, unplanned read- mission or unplanned reoperation. Demographics, postoperative recovery and compliance were compared of those ERAS failure groups to the ERAS success group. Results: ERAS failure occurred in 59 patients, 33 of whom had prolonged hospital stay, 18 were readmitted to hospital within 30 days after discharge, and 8 accepted reoperation. Preoperative American Society of Anesthesiologists (ASA) score of ≥III (OR = 2.736;95% CI: 1.276 6.939;P=0.028) and albumin (ALB) level of <35g/L (OR=3.589;95% CI: 1.403 9.181;P=0.008) were independent risk factors associated with prolonged hospital stay. Elderly patients (>70 years) were on a high risk of unplanned reoperation (62.5% vs. 23.1%, P=0.026). Patients with prolonged hospital stay and unplanned reoperation had delayed intake and increased intolerance of oral foods. Prolonged stay patients got off bed later than ERAS success patients did (65h vs. 46h, P =0.012). Unplanned reoperation patients tended to experience severer pain than ERAS success patients did (3 score vs. 2 score, P =0.035). Conclusions: Patients with high ASA score, low ALB level or age >70 years were at high risk of ERAS failure in pancreaticoduodenectomy. These preoperative demographic and clinical characteristics are important determinants to obtain successful postoperative recovery in ERAS program.

Intratumoral heterogeneity of hepatocellular carcinoma: From singlecell to population-based studies

Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)largely influences the efficacy of therapies in individuals.ITH contributes to tumor growth,metastasis,recurrence,and drug resistance and consequently limits the prognosis of patients with HCC.There is an urgent need to understand the causes,characteristics,and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival.Here,we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity.In parallel,evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem.We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions,combined with population-based clinical trials,will help to clarify the clinical implications of ITH,develop novel intervention strategies,and improve patient prognosis.

Probable sirolimus-induced rupture of arterial anastomosis after liver transplantation in a patient intolerant of tacrolimus

To the Editor:Liver transplantation remains the only cure for end-stage liver disease.Tacrolimus is widely used as a first-line immunosuppressive drug to prevent organ rejection after liver transplantation[1–3].However,tacrolimus has a narrow therapeutic index and wide inter-individual variability in pharmacokinetics,which can result in underimmunosuppression or toxicity.Orally administered tacrolimus is rapidly absorbed from the distal gastrointestinal tract and extensively metabolized in the liver and intestinal walls by cytochrome P450(CYP)3A4 and 3A5[2,4,5].

细胞与基因治疗中大片段的DNA精准插入研究进展

Cell and gene therapy(CGT)shows great therapeutic potential for diverse diseases such as hereditary diseases,cancer,and infectious diseases,with more than 40 food and drug administration(FDA)-approved drugs and lots in preclinical or clinical trials.In the scenario of cell therapy,cells typically isolated from the patients or healthy donors are functionally enhanced in vitro via genome editing before infusion back to patients.

Emerging new therapeutic antibody derivatives for cancer treatment

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells.The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies,such as antibody fragments,bispecific antibodies,and antibody derivatives(e.g.,antibody-drug conjugates and immunocytokines).