Nomogram for prediction of hepatocellular carcinoma recurrence after liver resection.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality. Liver resection (LR) is a curative treatment for early-stage HCC, but the prognosis of HCC patients after LR is unsatisfactory because of tumor recurrence. Prognostic prediction models with great performance are urgently needed. The present study aimed to establish a novel prognostic nomogram to predict tumor recurrence in HCC patients after LR. METHODS: We retrospectively analyzed 726 HCC patients who underwent LR between October 2011 and December 2016. Patients were randomly divided into the training cohort (n = 508) and the testing cohort (n = 218). The protein expression of 14 biomarkers in tumor tissues was assessed by immunohistochemistry. The nomogram predicting recurrence-free survival (RFS) was established by a multivariate Cox regression analysis model and was evaluated by calibration curves, Kaplan-Meier survival curves, time-dependent areas under the receiver operating characteristic (ROC) curves (AUCs), and decision curve analyses in both the training and testing cohorts. RESULTS: Alpha-fetoprotein [hazard ratio (HR) = 1.013, P = 0.002], portal vein tumor thrombosis (HR = 1.833, P < 0.001), ascites (HR = 2.024, P = 0.014), tumor diameter (HR = 1.075, P < 0.001), E-cadherin (HR = 0.859, P = 0.011), EMA (HR = 1.196, P = 0.022), and PCNA (HR = 1.174, P = 0.031) immunohistochemistry scores were found to be independent factors for RFS. The 1-year and 3-year AUCs of the nomogram for RFS were 0.813 and 0.739, respectively. The patients were divided into the high-risk group and the low-risk group by median value which was generated from the nomogram, and Kaplan-Meier analysis revealed that the high-risk group had a shorter RFS than the low-risk group in both the training (P < 0.001) and testing cohorts (P < 0.001). CONCLUSIONS: Our newly developed nomogram integrated clinicopathological data and key gene expression data, and was verified to have high accuracy in predicting the RFS of HCC patients after LR. This model could be used for early identification of patients at high-risk of postoperative recurrence.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

Clinical analysis of Wernicke encephalopathy after liver transplantation.

BACKGROUND: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation. METHODS: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed. RESULTS: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia. CONCLUSIONS: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.

Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience.

BACKGROUND: Biliary mucinous cystic neoplasms (BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. METHODS: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. RESULTS: Among the 49 patients, 37 were female (75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients (44.9%) had no symptoms. Serum carbohydrate antigen (CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34 (70.8%) had low-grade intraepithelial neoplasms (LGINs), and 14 (29.2%) had high-grade intraepithelial neoplasms (HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin (CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival (OS) of BMCNs was not reached. The longest survival time was 137 months.The 5- and 10-year OS rates were 100% and 85.4%, respectively. The 5- and 10-year recurrence-free survival (RFS) rates were 93.9% and 80.2%, respectively. CONCLUSIONS: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS: From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS: The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS: The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.

Exosome is involved in liver graft protection after remote ischemia reperfusion conditioning.

BACKGROUND: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats. METHODS: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated. RESULTS: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group. CONCLUSIONS: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic structure.

BACKGROUND: Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). METHODS: A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. RESULTS: A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. CONCLUSIONS: Transplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma.

BACKGROUND: Hyperlipidemia is a common complication after liver transplantation (LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. METHODS: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. RESULTS: Early posttransplant hypercholesterolemia (EPHC) was independently inversely associated with the risk of recurrence [hazard ratio (HR) = 0.630; P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC (B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence (HR = 0.504; P = 0.006) and mortality (HR = 0.511; P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival (89.6% and 83.7% vs. 83.8% and 72.7% respectively; P = 0.023), and 1-year and 3-year overall survival (95.8% and 84.8% vs. 94.6% and 77.6% respectively; P = 0.039). In the subgroup analysis, B-EPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria; whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC (recurrence HR = 0.306, P = 0.011; mortality HR = 0.325, P = 0.031). CONCLUSIONS: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.

A mixed blessing for liver transplantation patients - Rapamycin.

BACKGROUND: Liver transplantation (LT) is an effective treatment option for end-stage liver disease. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, are widely used post LT. DATA SOURCES: In this review, we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT. The literature available on PubMed for the period of January 1999-September 2022 was reviewed. The key words were rapamycin, sirolimus, liver transplantation, hepatocellular carcinoma, diabetes, and lipid metabolism disorder. RESULTS: Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens. It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma (HCC) recurrence post LT. Rapamycin is closely related to two long-term complications after LT, diabetes and lipid metabolism disorders. CONCLUSIONS: Rapamycin prevents HCC recurrence post LT in some patients, but it also induces metabolic disorders. Reasonable use of rapamycin benefits the liver recipients.

Three-dimensional modeling in complex liver surgery and liver transplantation.

Liver resection and transplantation are the most effective therapies for many hepatobiliary tumors and diseases. However, these surgical procedures are challenging due to the anatomic complexity and many anatomical variations of the vascular and biliary structures. Three-dimensional (3D) printing models can clearly locate and describe blood vessels, bile ducts and tumors, calculate both liver and residual liver volumes, and finally predict the functional status of the liver after resection surgery. The 3D printing models may be particularly helpful in the preoperative evaluation and surgical planning of especially complex liver resection and transplantation, allowing to possibly increase resectability rates and reduce postoperative complications. With the continuous developments of imaging techniques, such models are expected to become widely applied in clinical practice.