Nomogram to predict liver surgery-specific complications for hepatocellular carcinoma: A multicenter study.

BACKGROUND: Early identification of patients at risk for surgical complications enables surgeons to make better treatment decisions and optimize resource utilization. We propose to develop a nomogram for predicting the risk of moderate-to-severe liver surgery-specific complications after hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: We retrospectively enrolled HCC patients who underwent radical hepatectomy at four medical centers from January 2014 to January 2019 in southwestern China, randomly (7:3) divided into training and validation cohorts. We used least absolute shrinkage and selection operator (LASSO) logistic regression to build a nomogram model. RESULTS: The nomogram model contained 6 variables: diabetes mellitus (yes vs. no, OR: 2.32, 95% CI: 1.16-4.64, P = 0.02), major hepatectomy (yes vs. no, OR: 2.65, 95% CI: 1.64-4.27, P < 0.001), platelets (PLT, ≥100 × 103/µl vs. <100 × 103/µl, OR: 0.53, 95% CI: 0.33-0.87, P = 0.01), prothrombin time (PT, >13 s vs. ≤13 s, OR: 1.78, 95% CI: 1.04-3.05, P = 0.04), albumin-indocyanine green evaluation grade (ALICE grade, grade B vs. grade A, OR: 2.06, 95% CI: 1.17-3.61, P = 0.01), and prognostic nutrient index (PNI, >48 vs. ≤48, OR: 0.55, 95% CI: 0.33-0.92, P = 0.02). The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were 0.751 (95% CI, 0.703-0.799) and 0.743 (95% CI, 0.653-0.833) for the training and validation cohorts, respectively. Decision curve analysis (DCA) showed that the nomogram had good clinical value. CONCLUSION: We provide good preoperative predictors for the risk of moderate-to-high FABIB score complications in patients with HBV-related HCC posthepatectomy.

The application and prospection of augmented reality in hepato-pancreato-biliary surgery.

Augmented Reality (AR) is one of the main forms of Extended Reality (XR) application in surgery. hepato-pancreato-biliary (HPB) surgeons could benefit from AR as an efficient tool for making surgical plans, providing intraoperative navigation, and enhancing surgical skills. The introduction of AR to HPB surgery is less than 30 years but brings profound influence. From the early days of projecting liver models on patients' surfaces for locating a better puncture point to today's assisting surgeons to perform live donor liver transplantation, a series of successful clinical practices have proved that AR can play a constructive role in HPB surgery and has great potential. Thus far, AR has been shown to increase efficiency and safety in surgical resection, and, at the same time, can improve oncological outcomes and reduce surgical risk. Although AR has presented admitted advantages in surgery, AR's application is still immature as an emerging technique and needs more exploration. In this paper, we reviewed the principles of AR and its developing history in HPB surgery, describing its significant practical applications over the past 30 years. Reviewing the past attempts of AR in HPB surgery could make HPB surgeons a better understanding of future surgery and the digital trends in medicine. The routine uses of AR in HPB surgery, as an indication of the operating room entering the new era, is coming soon.

An integrated map of fibroblastic populations in human colon mucosa and cancer tissues.

Fibroblasts and myofibroblasts are major mesenchymal cells in the lamina propria of colon mucosa and in colon cancer tissues. Detailed insight into the highly specific populations of fibroblasts and myofibroblasts is required to understand the integrity and homeostasis of human colon mucosa and colon cancer. Based on gene expression profiles of single cells, we identified fibroblast populations that produce extracellular matrix components, Wnt ligand- and BMP-secreting fibroblasts, chemokine- and chemokine ligand-generating fibroblasts, highly activated fibroblasts, immune-modulating fibroblasts, epithelial cell-modulating myofibroblasts, stimuli-responsive myofibroblasts, proliferating myofibroblasts, fibroblast-like myofibroblasts, matrix producing myofibroblasts, and contractile myofibroblasts in human colon mucosa. In colon cancer tissue, the compositions of fibroblasts and myofibroblasts were highly altered, as were the expressing patterns of genes including BMPs, Wnt ligands, chemokines, chemokine ligands, growth factors and extracellular matrix components in fibroblasts and myofibroblasts. Our work expands the working atlas of fibroblasts and myofibroblasts and provides a framework for interrogating the complexity of stromal cells in human healthy colon mucosa and colon cancer tissues.

Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study.

AIMS: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort. CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

The Effect of Metabolic Syndrome on the Outcome of Hepatitis B-Associated Hepatocellular Carcinoma Patients After Hepatectomy: A Multicenter Study.

Background and Aims: With changes in dietary patterns and modern lifestyles, the prevalence of metabolic syndrome (MetS) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients is increasing. The purpose of our study is to explore the impact of MetS on the prognosis of HBV-associated HCC patients following radical hepatectomy. Methods: Data on consecutive HCC patients who underwent radical hepatectomy were prospectively obtained and retrospectively analyzed from seven medical centers in west areas of China. Propensity score matching (PSM) analysis was conducted to balance the heterogeneity between MetS-HBV-HCC group and HBV-HCC group. Surgical outcomes have been contrasted between the two groups. Results: In 984 patients, 179 (18.19%) were diagnosed with MetS. Patients in the MetS-HBV-HCC group had higher CCI score (8.7 [0.0, 12.2] vs. 0.0 [0.0, 8.7], p = 0.048) and a higher rate of severe complications (Clavien-Dindo ≥3, 7.82% vs. 4.10%, p = 0.035), to be more precise: postoperative liver failure, hydrothorax, and hyperglycemia. Patients in the MetS-HBV-HCC group tended to have worse 5-year overall survival (OS) rate (61.45% vs. 69.94%, p = 0.027) and recurrence-free survival (RFS) rate (62.57% vs. 53.66%, p = 0.030), consistent with the results of the competing risk models. Last, MetS was identified to be an independent unfavorable prognostic factor in the multivariate analysis. Conclusion: The involvement of MetS increased the risk of postoperative complications and worsens the overall survival and recurrence-free survival time, reminding us to be more prudent to face metabolic disorder among tumor patients.

IL-6-induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: IL-6-induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL-6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. APPROACH AND RESULTS: High-throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL-6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up-regulated by IL-6 treatment in a time and concentration-dependent manner. The biogenesis of cGGNBP2 was regulated by RNA-binding protein DEx-H Box Helicase 9, which was also mediated by IL-6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2-184aa encoded by cGGNBP2. cGGNBP2-184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2-184aa directly interacted with signal transducers and activators of transduction-3 (STAT3), phosphorylated STAT3Tyr705 , and played a positive regulatory role in modulating IL-6/STAT3 signaling. IL-6/cGGNBP2-184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL-6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. CONCLUSIONS: Our study demonstrates that cGGNBP2-184aa, a protein encoded by IL-6-induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL-6/STAT3-targeting treatments in ICC.

Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy.

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS: Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

Comparison of nucleoside and nucleotide analogs in the recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection: A multicenter study.

BACKGROUND: Antiviral therapy should reduce the recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) after surgical resection. However, there is little research on whether various antiviral drugs have different prognostic effects in patients with HBV-related HCC after curative liver resection. The present study compared the effects of nucleotide analog (NtA) and nucleoside analog (NsA) antiviral therapies after surgical resection on the prognosis of HBV-related HCC. METHODS: A total of 1303 patients with HBV-related HCC who received curative hepatectomy at five institutes between April 2014 and April 2019 were retrospectively enrolled and analyzed. Propensity matching analysis was used to compare the outcomes of HCC patients given NsA versus NtA therapy. Subgroup analysis of patients treated with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) was also performed. RESULTS: Among 1303 patients, 759 (58.2%) patients developed recurrence, and 460 (35.3%) patients died. Multivariable analyses revealed that NtA therapy significantly decreased the risk of HCC recurrence (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51-0.80; p < 0.001) and HCC-related death (HR, 0.52; 95% CI, 0.36-0.76; p = 0.001) compared to that with NsA therapy. Subgroup analysis showed that TDF treatment was associated with significantly lower rates of HCC recurrence (HR, 0.64; 95% CI, 0.49-0.83; p = 0.001) and death (HR, 0.32; 95% CI, 0.20-0.50; p < 0.001) than ETV treatment. CONCLUSIONS: Nucleotide analog treatment, but not NsA treatment, significantly reduced the risk of HCC recurrence in patients with HBV-related HCC and improved overall survival after curative hepatic resection.

Baseline HBV-DNA load plus AST/ALT ratio predicts prognosis of HBV-related hepatocellular carcinoma after hepatectomy: A multicentre study.

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV-related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA load and AST/ALT ratio. Based on the HBV-DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5-year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5-year OS of 42.7%. Similarly, the four types had statistically different recurrence-free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p < .001) and long-term survival (HR: 1.574, p = .001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, the classfication based on baseline HBV-DNA load and AST/ALT ratio could effectively stratify HBV-related HCC patients with distinguishable prognoses after hepatectomy.

Combination of albumin-globulin score and skeletal muscle index predicts long-term outcomes of intrahepatic cholangiocarcinoma patients after curative resection.

BACKGROUND & AIMS: Sarcopenia is characterized by loss of skeletal muscle mass and associated with poor postoperative outcomes. This study aimed to investigate the prognostic value of preoperative albumin-globulin score (AGS), skeletal muscle index (SMI) as well as their combination in patients with intrahepatic cholangiocarcinoma (ICC) treated with surgical resection. METHODS: A total of 613 newly diagnosed ICC patients from two centers were retrospectively analyzed (460 in discovery cohort and 153 in validation cohort). The plain computed tomography images were used to measure SMI. The effect of AGS, SMI and CAS grade on clinicopathological characteristics and long-term outcomes of patients with ICC were analyzed. RESULTS: The SMI was significantly greater in males than in females. Patients with decreased AGS, increased SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS). Stratefied by CAS grade, 68 (14.8%) patients in grade 1 were associated with increased body mass index (BMI) and best postoperative prognosis, whereas 194 (42.1%) patients in grade 3 were linked to worst OS and RFS. The CAS grade showed a promising accuracy in predicting OS and RFS of ICC patients (area under curves [AUCs] were 0.732 and 0.768). Multiple tumors, MVI and elevated CAS grades were identified as independent risk factors for OS and RFS of ICC patients. These results were confirmed by validation cohort. CONCLUSION: The present study provided compelling evidence that a novel index based on combination of preoperative AGS and SMI was closely related to postoperative long-term outcomes for surgically treated ICC patients. Preoperative evaluation of CAS grade may be useful for risk classification and clinical therapeutic decision-making for ICC patients.

Complete embolisation of the proper hepatic artery for delayed haemorrhage after pancreaticoduodenectomy: a case report.

Postpancreatectomy haemorrhage (PPH) is a rare and life-threatening complication that can occur after pancreaticoduodenectomy (PD). Recently, radiological intervention has become a first-line approach for the diagnosis and treatment of late PPH in haemodynamically stable patients. Surgical intervention should be performed in haemodynamically unstable patients. We report the case of a 54-year-old man who underwent PD for ampullary carcinoma. On postoperative day (POD) 20, he developed a late PPH in the context of pancreatic fistula that was accompanied by hypotension and tachycardia. Therefore, emergency relaparotomy was performed, but the bleeding site was not detected due to severe adhesions in the surgical field. Thus, urgent angiography was performed immediately, and active bleeding was detected from the distal part of the proper hepatic artery. Coil embolisation of the proper hepatic artery trunk was successfully performed. No intrahepatic abscess or liver failure was subsequently observed, and the patient left our hospital on POD 27. This case shows that radiological intervention is a first choice for the diagnosis and treatment of haemodynamically stable late PPH and that it also might still be a first choice and also be safer and more effective than surgical intervention even with unstable haemodynamics.

The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis.

BACKGROUND: The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. METHODS: All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. RESULTS: Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. CONCLUSION: Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.

[Treatment of Stroke Patients with Shoulder-wrist Syndrome by Acupoint Catgut Embedding and Surface Electromyogram Biofeedback Therapy].

OBJECTIVE: To observe the clinical effectiveness of acupoint catgut embedding and surface electromyogram biofeedback therapy (sEMGBF) in the treatment of stroke patients complicated with shoulder-hand syndrome (SHS). METHODS: A total of 90 stroke patients with SHS were randomly divided into acupoint catgut embedment (ACE), sEMGBF and ACE+sEMGBF (combined treatment) groups (n=30 cases/group). The catgut embedment was performed at Jianliao (LI 14), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5) on the affected side, once every 3 weeks, twice altogether. The electromyographic biofeedback therapy (30-50 Hz, pulse duration 200 µs, 6 s-on and 10 s-off, appropriate strength) was applied to the skin area co-vering the deltoid muscle, flexor muscle of wrist and wrist extensor for 20 min, once per day, 5 times/week, for 6 weeks. The total effective rate was assessed by using Liao's and Zhu's methods (1996), the pain severity assessed using visual analogue scale (VAS), and Fugl-Meyer assessment (FMA, 66-points) scale and the patients' activities of daily living function (ADL, 100-points) were also scored. RESULTS: Before treatment, the VAS, FMA and ADL points of the three groups were not significantly different (P>0.05). After the treatment, the total effective rate (93.33%), FMA and ADL scores of the combined treatment group were significantly higher than those of the ACE and sEMGBF groups (P<0.05), while the VAS score of the combined treatment group was significantly lower than those of the ACE and sEMGBF groups (P<0.05). The total effective rates, FMA and ADL scores of the ACE and sEMGBF groups were comparable (P>0.05). The VAS score of the ACE group was markedly lower than that of the sEMGBF group (P<0.05). CONCLUSION: The combined administration of ACE and sEMGBF has a better therapeutic effect for stroke patients complicated with SHS relevant to simple ACE and simple sEMGBF therapy in improving the upper limb function, relieving pain, and enhancing the daily life quality.