Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

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.

Comparison of long-term outcomes of splenectomy with periesophagogastric devascularization and transjugular intrahepatic portosystemic shunt in treating cirrhotic portal hypertension patients with recurrent variceal bleeding.

PURPOSE: Transjugular intrahepatic portosystemic shunt (TIPS) and splenectomy with periesophagogastric devascularization (SPD) are widely used to treat cirrhotic portal hypertension (PH) and prevent variceal rebleeding. However, direct comparisons between these two approaches are rare. This study was designed to compare the long-term outcomes of TIPS and SPD in patients with cirrhotic PH and variceal rebleeding. METHODS: The study included cirrhotic PH patients with a history of gastroesophageal variceal bleeding between 18 and 80 years of age who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to January 2022. Patients were enrolled into two groups according to TIPS or SPD was performed. Baseline characteristics were matched using propensity score matching (PSM). RESULTS: A total of 230 patients underwent TIPS, while 184 underwent SPD. PSM was carried out to balance available covariates, resulting in a total of 83 patients in the TIPS group and 83 patients in the SPD group. Patients in SPD group had better liver function during 60 months follow-up. Five-year overall survival rates in SPD group and TIPS group were 72 and 27%, respectively, at 2 years were 88 and 86%, respectively. The 2- and 5-year freedom from variceal rebleeding rates were 95 and 80% in SPD group and 80 and 54% in TIPS group. CONCLUSIONS: SPD is clearly superior to TIPS in terms of OS and freedom from variceal rebleeding in patients with cirrhotic PH. In addition, SPD improved liver function in patients with cirrhotic PH.

Prognostic significance of gamma-glutamyl transpeptidase to albumin ratio in patients with intrahepatic cholangiocarcinoma after hepatectomy.

Inflammation has been reported to play an important role in tumour progression and prognosis. In this study, we evaluated the prognostic significance of γ-glutamyl transpeptidase (GGT) to albumin ratio (GAR) in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. We retrospectively analysed 650 ICC patients underwent hepatectomy at three Chinese medical centres between January 2009 and September 2017. Patients were classified into derivation cohort (n = 509) and validation cohort (n = 141). Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for GAR. Survival curve and cox regression analysis were applied to assess the prognostic power of GAR. The prognostic accuracy of GAR was compared with other variables by ROC curve. The optimal cut-off value for GAR was 1.3655. Preoperative high GAR was closely related to tumour number, lymph node invasion and GGT. The survival curve of derivation and validation cohorts showed that patients in the high GAR group had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients in the low GAR group. Multivariate analysis in the derivation cohort confirmed that GAR was an independent prognostic factor for survival outcomes. Moreover, the ROC curve revealed that GAR had better predictive accuracy than other variables. High GAR predicted poor OS and DFS in ICC patients after hepatectomy. GAR may be a novel, simple and effective prognostic marker for ICC patients.

Application of associating liver partition and portal vein ligation for staged hepatectomy for initially unresectable hepatocellular carcinoma.

OBJECTIVE: To evaluate the safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of initially unresectable hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and to preliminarily explore the mechanism of rapid growth of the future liver remnant (FLR). METHODS: Twenty-four patients with HBV-associated HCC who underwent ALPPS in our hospital from August 2014 to January 2021 were retrospectively studied. Propensity score matching was used to compare oncologic outcomes of patients treated with ALPPS and transarterial chemoembolization (TACE). The expression of YAP and JNK in liver tissue after two stages of ALPPS were detected. RESULTS: The median standard liver volume (SLV) was 1471.4 ml. Before second stage of ALPPS, the median FLR increased by 74.4%, and the median FLR/SLV increased from 26.1 to 41.6%. Twenty-two patients (91.7%) received staged hepatectomy after a median interval of 15 (9-24) d. The total incidence of postoperative complications in ALPPS group was 54.5%, and of Clavien-Dindo ≥ IIIb postoperative complications (requiring surgical, endoscopic or radiological intervention under general anesthesia) was 9.1%. There was no significant difference in total complications between ALPPS group and TACE group, but there were lower rate of above grade III complications in the TACE group than that in the ALPPS group. The incidence of complications was lower in laparoscopic-ALPPS than that in open surgery. In ALPPS group, the 1-year, 2-year and 5-year overall survival rate were respectively 71.4%, 33.3% and 4.8%. Interval time was an independent risk factor associated with overall survival rate. There was no significant difference in overall survival rate between ALPPS group and TACE group. For advanced HCC (BCLC stage B and C), ALPPS group was not superior to TACE group in overall survival rate. The expression of YAP and p-JNK in the residual liver tissue after second stage procedure was higher than that after first stage procedure, and the co-expression of YAP and p-JNK was observed in the residual liver tissue. CONCLUSION: ALPPS is a safe and effective treatment for initially unresectable HBV-associated HCC. Laparoscopic technique might improve the effect of ALPPS. YAP and JNK pathway might take a role in rapid FLR increase in ALPPS procedure.

Tumor location influences perioperative and oncologic outcomes in solitary intrahepatic cholangiocarcinoma following curative resection: a multi-center analysis.

BACKGROUND: To compare perioperative and oncologic outcomes of patients with different locations of intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 352 ICC patients underwent curative intent hepatectomy were included. Clinical outcomes were compared between ICC patients with tumors located at subcapsular and non-subcapsular, perihepatic vein (pHV) and non-pHV, or periportal vein (pPV) and non-pPV. Kaplan-Meier curves were used to evaluate the influence of tumor location on survival outcomes. RESULTS: Surgical procedures for pPV ICC were associated with longer operative time and elevated intraoperative blood loss compared to non-pPV. Patients with pPV ICC significantly correlated to increased frequency of log odds of positive lymph nodes (LODDS) classification 3-4. In addition, the ICC located at pPV was correlated with both worse overall survival (OS) and disease-free survival (DFS) compared to non-pPV, whereas no significant difference was observed between subcapsular and non-subcapsular or between pHV and non-pHV. CONCLUSIONS: A pPV location contributed to poor perioperative outcomes and quick tumor recurrence for patients with solitary ICC undergoing curative resection. A pPV location also contributed to regional lymph node metastases and was a risk factor for intrahepatic recurrence. Subcapsular and pHV locations did not influence clinical outcomes of ICC patients.

Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma.

BACKGROUND: This study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach. RESULTS: 95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016). CONCLUSION: PSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.

Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated inhibition of CCR2.

Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the sphingosine kinase (SphK)1-dependent effect on liver fibrosis. The levels of expression and activity of SphK1 were significantly increased in fibrotic livers compared with the normal livers in human. SphK1 was coexpressed with a range of HSC/KC markers including desmin, α-smooth muscle actin (α-SMA) and F4/80 in fibrotic liver. Deficiency of SphK1 (SphK1-/- ) resulted in a marked amelioration of hepatic injury, including transaminase activities, histology, collagen deposition, α-SMA and inflammation, in CCl4 or bile duct ligation (BDL)-induced mice. Likewise, treatment with a specific inhibitor of SphK1, 5C, also significantly prevented liver injury and fibrosis in mice induced by CCl4 or BDL. In cellular levels, inhibition of SphK1 significantly blocked the activation and migration of HSCs and KCs. Moreover, SphK1 knockout in KCs reduced the secretion of CCL2, and SphK1 knockout in HSCs reduced C-C motif chemokine receptor 2 ([CCR2] CCL2 receptor) expression in HSCs. CCL2 in SphK1-/- mice was lower whereas microRNA-19b-3p in SphK1-/- mice was higher compared with wild-type (WT) mice. Furthermore, microRNA-19b-3p downregulated CCR2 in HSCs. The functional effect of SphK1 in HSCs on liver fibrosis was further strengthened by the results of animal experiments using a bone marrow transplantation (BMT) method. CONCLUSION: SphK1 has distinct roles in the activation of KCs and HSCs in liver fibrosis. Mechanistically, SphK1 in KCs mediates CCL2 secretion, and SphK1 in HSCs upregulates CCR2 by downregulation of miR-19b-3p. (Hepatology 2018).

NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation.

Hypoxic environment has been suggested in stem cell culturing as their physiologic niche requires oxygen tension to maintain stemness. The administration of cobalt chloride (CoCl2) was widely applied in mimicking hypoxia for its economic advantages and convenience. We confirmed that CoCl2 could maintain stemness and promote the osteogenesis capacity of MSCs. However, CoCl2 could induce the apoptosis and hinder the proliferation of MSCs. To find out a potential method maintaining their stemness without threatening their survival, we analyzed the database of Gene Expression Omnibus (GEO) and proposed that NRF2 (nuclear factor erythroid-derived 2-like 2) might be the potential target. We found that knocking down NRF2 expression in MSCs impaired the expression of stem cell markers and the osteogenesis process even under hypoxic environment, but with NRF2 overexpression, the proliferation of MSCs was increased with significantly reduced rate of apoptosis. Therefore, our findings suggested that overexpressing NRF2 could be a potential method for maintaining stemness and preventing apoptosis in MSCs under oxidative stress.

Therapeutic potentials of umbilical cord-derived mesenchymal stromal cells for ischemic-type biliary lesions following liver transplantation.

BACKGROUND AIMS: Ischemic-type biliary lesions are severe, graft-threatening complications after orthotopic liver transplantation, and a novel and efficient therapeutic strategy is urgently needed. Due to the immunosuppressive and regenerative properties, mesenchymal stromal cells (MSCs) could be an interesting candidate. METHODS: We initiated safety and efficacy of human umbilical cord-derived MSC (UC-MSC) transfusions for patients with ischemic-type biliary lesions after liver transplantation. From January 2013 to June 2014, 12 ischemic-type biliary lesions patients were recruited as the MSCs group in this phase I, prospective, single-center clinical study. Patients in this group received six doses of UC-MSCs (about 1.0 × 106 MSCs per kilogram body weight through peripheral intravenous infusion). The traditional therapeutic protocol was applied during October 2003 to December 2012 in 70 ischemic-type biliary lesions patients who were treated as the control group. Liver function tests, the need for interventional therapies and graft survival rate were chosen to evaluate the therapeutic efficacy of MSC treatment. Adverse events were closely monitored up to 2 years after MSC transfusions. RESULTS: No significant MSC-related adverse events were observed during the trial. Compared with baseline, the levels of total bilirubin, γ-glutamyl transferase and alkaline phosphatase were decreased after UC-MSC treatment at week 20 and week 48. Interventional therapies were performed in 64.3% (45/70) of patients in the control group and 33.3% (4/12) of patients in the MSCs groups. MSC therapy significantly decreased the need for interventional therapies (P = 0.046). The 1- and 2-year graft survival rates were higher in the MSCs group (100% and 83.3%, respectively) than in the control group (72.9% and 68.6%, respectively). CONCLUSIONS: The UC-MSC transfusions are clinically safe and short-term favorable, which may become a novel treatment for patients with ischemic-type biliary lesions after liver transplantation.

Hippo (YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion. METHODS: Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. RESULTS: Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). CONCLUSIONS: YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

JNK signaling mediates acute rejection via activating autophagy of CD8+ T cells after liver transplantation in rats.

Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear. Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored. Results: The expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex. Conclusion: JNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.

Diagnostic performance of PIVKA-II in identifying recurrent hepatocellular carcinoma following curative resection: a retrospective cohort study.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p < 0.001; AFP: 4.90 vs. 3.00 ng/ml, p < 0.001) and there is a significant correlation between PIVKA-II and AFP (R = 0.901, p < 0.001). PIVKA-II showed better accuracy than AFP in the diagnosis of overall recurrent HCC (AUC: 0.883 vs. 0.672; p < 0.0001), but also in patients with negative PIVKA-II before curative resection (AUC: 0.878 vs. 0.680, p = 0.001). Clinician should pay more attention to serum PIVKA-II values when following patients after curative HCC resection to detect early recurrence.Clinical trial registration: ChiCTR2300070874.

Health-related quality of life after liver transplantation: the experience from a single Chinese center.

BACKGROUND: Few studies have been performed to assess health-related quality of life (HRQOL) in liver transplantation (LT) patients in the mainland of China. This study aimed to investigate the HRQOL of post-LT patients in a single center. METHODS: HRQOL was evaluated by the SF-36 (Chinese version) questionnaire in 60 patients (LT group) who had received LT for benign end-stage liver disease (BELD). Fifty-five patients with BELD (BELD group) and 50 healthy volunteers from the general population (GP group) were also evaluated, and the results were compared among the three groups. RESULTS: There was a significant difference among the three groups in terms of the scores of eight domains in the SF-36 (P<0.01). Patients in the BELD group had lower scores in each domain of the SF-36 in comparison with those in the GP group (P<0.025). The LT group had mental health scores equivalent to those of the BELD group (P>0.025), but higher scores for the remaining seven domains (P<0.025). Compared with the GP group, the LT group scored equivalently for role physical, body pain, vitality, social function and role emotion (P>0.025), but had lower scores for the remaining three domains (P<0.025). Lower family income was found to be associated with reduced physical function and mental health scores (P<0.05). Better education was associated with increased mental health scores (P<0.05). CONCLUSIONS: LT patients generally have a good HRQOL although some respects of their HRQOL remains to be improved. Lower family income and poor education are important factors relating to the poor HRQOL of LT patients.

[Alterations of immune status in liver transplant patients with sepsis].

OBJECTIVE: To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents. METHODS: A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis: A. sepsis after transplantation (TS, n = 11), B. severe sepsis after transplantation (TSS, n = 10), C. sepsis without transplantation (NTS, n = 15) and D. severe sepsis without transplantation (NTSS, n = 11). Ten healthy volunteers were selected as the control group. Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte. RESULTS: The APACHII and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01). In addition, SOFA score in TSS group was significantly higher than that in NTSS group (17.0 ± 4.5 vs 12.1 ± 2.8, P < 0.01). The percentages of T cell in 4 groups were all significantly lower than healthy volunteers (all P < 0.01). The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups (P = 0.095). As compared with the control group, the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 ± 0.012, 0.047 ± 0.018 vs 0.062 ± 0.006) while the level of IL-10 was higher ((32.6 ± 7.5), (25.9 ± 4.3) vs (8.2 ± 1.4) ng/L, all P < 0.05). And the difference was more significant in the TSS group. As compared with the healther, the percentage of CD4(+)CD25(+)Foxp3(+)Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%, P < 0.01), and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ± 0.52%, P = 0.003). No significant difference existed in the percentage of Treg between the TS and control groups (P = 0.398). And it was significantly higher that in the TSS group (5.16% ± 0.99% vs 4.06% ± 0.52%, P = 0.006). But the magnitude of increase level was not so great as that in the NTSS group. The changes of Foxp3 mRNA demonstrated the similar trend as the percentage of Treg. CONCLUSIONS: The immune states of transplant recipients with sepsis are comparable with healthy persons during sepsis. It may subsequently develop into serious immunosuppression. Immunosuppressant should be withdrawn in severe sepsis stage so as to reconstitute the immune system.

[Reproduction after liver transplantation: a report of 13 cases from a single Chinese center].

OBJECTIVE: To explore the recipient's reproduction after liver transplantation (LT) and assess the outcomes of their offspring. METHODS: We retrospectively analyzed the reproduction status of 13 post-LT patients among 336 post-LT recipients during a follow-up period. Physical and intellectual status of their offspring were evaluated by developmental index and Denever developmental screening test. RESULTS: A total of 16 children were mothered or fathered by 13 LT patients. Two female patients mothered a boy and a girl. Ten male patients fathered 6 male and 8 female children while another male fathered a child at 28 gestational weeks. Eleven patients fathered the first gestation 21 mon (medium) since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean gestation age of (38.2 ± 1.8) weeks, with a mean birth weight of (3.1 ± 0.5) kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was found. Thirteen of 16 children had almost normal developmental indices and ten had almost normal Denever developmental screening. CONCLUSION: Post-LT patients of reproductive age are able to reproduce offspring. The short-term development of their offspring is relatively normal.

Tumor Burden Score Stratifies Prognosis of Patients With Intrahepatic Cholangiocarcinoma After Hepatic Resection: A Retrospective, Multi-Institutional Study.

Background: The prognostic significance of tumor burden score (TBS) on patients who underwent curative-intent resection of intrahepatic cholangiocarcinoma (ICC) has not been evaluated. The present study aimed to investigate the impact of TBS and its synergistic effect with CA19-9 (combination of TBS and CA19-9, CTC grade) on long-term outcomes. Methods: Patients who underwent radical resection of ICC between 2009 and 2017 were retrospectively identified from a multi-center database. The overall survival (OS) and recurrence-free survival (RFS) were examined in relation to TBS, serum preoperative CA19-9, and CTC grade. Results: A total of 650 patients were included in our study (509 in the derivation cohort and 141 in the validation cohort). Kaplan-Meier curves showed that both TBS and CA19-9 levels were strong predictors of survival outcomes. Patients with elevated TBS grade or elevated CA19-9 were associated with worse OS and RFS (both p < 0.001). As expected, CTC grade also performed well in predicting long-term outcomes. Patients with low TBS/low CA19-9 (CTC grade 1) were associated with the best OS as well as RFS, while high TBS/high CA19-9 (CTC grade 3) correlated to the worst outcomes. In the validation cohort, TBS grade, preoperative CA19-9, and CTC grade also stratified prognosis among patients (p < 0.001 for each). Conclusions: Both tumor morphology (tumor burden) and tumor-specific biomarker (serum CA19-9) were important when evaluating prognosis of patients with resectable ICC. Serum CA19-9 and TBS showed a synergistic effect on prognostic evaluation. CTC grade was a promising tool in stratifying prognosis of ICC patients after curative resection.

[Anxiety and depression for liver transplant recipients and their impact factors].

OBJECTIVE: To investigate the status of anxiety and depression for liver transplant (LT) recipients and explore their impact factors. METHODS: During the period of January 2005 to December 2008, the symptoms of anxiety and depression for 53 post-LT recipients (LT group) and 48 patients with benign end-stage liver disease (BELD group) were assessed by the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS). And they were compared with that of domestic norm (Norm group). The impact factors of anxiety and depression for LT recipients were analyzed by stepwise logistic regression. RESULTS: The anxiety scores of LT, BELD and Norm groups were (42 ± 9), (47 ± 11) and (30 ± 10) and the depression scores of three groups (48 ± 11), (52 ± 11) and (33 ± 9) respectively. The anxiety score was different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group (P < 0.01) while it was lower in the LT group than that in the BELD group (P < 0.05). The depression scores were different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group. And it was lower in the LT group than that in the BELD group (P < 0.05). The impact factor of anxiety for LT recipients was patient age and that of depression per capita monthly family income. CONCLUSION: The level of anxiety and depression of post-LT recipients is higher than that of domestic norm. The main impact factor for post-LT anxiety is patient age and that of depression per capita monthly family income.

[Preoperative neutrophil-lymphocyte ratio as a prognostic predictor after liver transplantation for hepatocellular carcinoma].

OBJECTIVE: To analyze the negative impact of preoperative neutrophil-lymphocyte ratio (NLR) on the tumor recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation. METHODS: The clinical data of HBV (hepatitis B virus)-associated HCC patients undergoing liver transplantation were retrospectively analyzed. Their clinical and pathological risk factors for tumor-free survival were evaluated by univariate analysis. The analysis of Cox multiple regression was performed to determine the parameters of predicting the HCC recurrence. NLR ≥ 2.5 was considered to be elevated. RESULTS: A total of 76 patients were identified. Among them, 37 had an elevated NLR. The 1, 3 and 5-year tumor-free survival rates were 69.2%, 52.7% and 50.9% respectively. The disease-free survival for patients with high NLR was significantly worse than that for those with normal NLR (1, 3, and 5 year survivals at 56.3%, 37.6% and 37.6% vs 81.1%, 66.9% and 63.3% respectively; P = 0.011). Univariate analysis of factors revealed that tumor size > 5 cm, tumor number > 3, vascular invasion, serum α-fetoprotein level ≥ 400 µg/L and NLR ≥ 2.5 were preoperative predictors of disease-free survival. Cox regression analysis showed that the presence of vascular invasion, tumor number > 3 and NLR ≥ 2.5 were independent prognostic factors of worse disease-free survival. CONCLUSION: An elevated NLR significantly increases the risk for tumor recurrence in HCC patients undergoing liver transplantation.

[Clinical analysis between "early" versus "late" liver retransplantation].

OBJECTIVE: To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively. RESULTS: Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05). CONCLUSIONS: The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.