Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study.

BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.

Association of Cholecystectomy With Liver Fibrosis and Cirrhosis Among Adults in the USA: A Population-Based Propensity Score-Matched Study.

Background and Aims: Cholecystectomy is the "gold standard" for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors. Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes. Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278-2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076-2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738-3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496-7.218). Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis.

Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States.

BACKGROUND AND AIMS: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals. METHODS: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC. RESULTS: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 µmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 µmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively. CONCLUSION: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases.

Totally laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes.

BACKGROUND: The traditional open or laparoscopic segmentectomy of liver segment 7 (S7) requires exposing and controlling the root of the right hepatic vein(RHV)after full mobilization and lifting up of the right liver before liver transection. This approach violates the "no-touch" principle for malignant tumors, and makes laparoscopic resection technically challenging. So reports on isolated totally laparoscopic anatomic S7 segmentectomy have rarely been reported. This study describes our experience in laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes of the liver. To our knowledge, this is the first description of this novel approach. METHODS: From September 2017 to May 2019, patients who underwent laparoscopic anatomic S7 segmentectomy for hepatocellular carcinoma at the HPB Surgery Department, Sun Yat-Sen Memorial Hospital entered into this retrospective study. This in situ split approach was designed using main vessels as the plane markers of right intersectoral and intersegmental planes, along which liver transection was carried out. There was no need to mobilize the right liver and control the root of RHV. RESULTS: There were 9 women and 15 men. The average diameter of the tumors on preoperative CT/MR was 3.4 cm (range 2-6 cm). All the procedures were successfully carried out laparoscopically. There was no perioperative death. The average operative time was 216.5 min (range 180-310 min). The average blood loss was 320 ml (range 120-620 ml). Pathological study showed all the operations to be R0 resections. CONCLUSION: Laparoscopic anatomic S7 segmentectomy using the in situ split approach resulted in R0 liver resection in all our patients with primary liver cancer. The operation was technically feasible and it provided a better view and increased maneuverability in the cramped operative space compared with the traditional open/laparoscopic approach. The approach also better complies with the "no-touch" principle for malignant tumors. Its long-term oncological outcomes require further studies.

Laparoscopic duodenum-preserving total pancreatic head resection: a novel surgical approach for benign or low-grade malignant tumors.

BACKGROUND: Duodenum-preserving total pancreatic head resection (DPPHRt) is an accepted alternative surgical procedure for benign or low-grade malignant tumors of the pancreatic head by preserving the duodenum with its intact blood supply from the pancreatic duodenal arterial arcade. This study describes our experience in laparoscopic DPPHRt (LDPPHRt). To our knowledge, this is the first description of this novel minimally invasive operation. METHODS: From August 2016 to May 2017, all consecutive patients who underwent LDPPHRt for pancreatic head lesions at the HPB Surgery Department, Sun Yat-Sen Memorial Hospital in Guangzhou, China were enrolled into this retrospective study. RESULTS: There were ten women and two men. The average age was 37.3 years (range 8-61 years). The average diameter of the pancreatic head lesions on pre-operative CT/MR was 3.7 cm (range 2-4.8 cm). All the LDPPHRt procedures were performed successfully. There was no peri-operative death. The average operative time was 272.5 min (range 210-320 min). The average blood loss was 215 ml (range 50-450 ml). Post-operative complications included pancreatic fistula grade B (two patients, or 16.7%) and biliary fistula (two patients, or 16.7%). All the complications responded well to conservative treatment. The mean post-operative hospital stay was 11.5 days (range 6-25 days). CONCLUSIONS: LDPPHRt provided a minimally invasive approach with good organ-preservation for benign or low-grade malignant tumors of the pancreatic head. The long-term oncological outcomes, and the exocrine and endocrine pancreatic functions after this operation require further studies.

Cabozantinib reverses multidrug resistance of human hepatoma HepG2/adr cells by modulating the function of P-glycoprotein.

BACKGROUND & AIMS: Cabozantinib, a small-molecule multitargeted tyrosine kinase inhibitor, has entered into a phase III clinical trial for the treatment of hepatocellular carcinoma (HCC). This study assessed the mechanistic effect of cabozantinib on the reversal of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). METHODS: CCK-8 assays and tumour xenografts were used to investigate the reversal of MDR in vitro and in vivo respectively. Substrate retention assays were evaluated by fluorescence microscope and flow cytometry. Western blotting was used to detect protein expression levels. mRNA expression was determined by qPCR. The ATPase activity of P-gp was investigated using Pgp-Glo(™) assay systems. The binding mechanism of cabozantinib to P-gp at the molecular level was evaluated using docking analysis. RESULTS: Cabozantinib enhanced the cytotoxicity of P-gp substrate drugs in HepG2/adr and HEK293-MDR1 cells but had no effect on non-P-gp substrates. In addition, cabozantinib increased the accumulation of P-gp substrates in HepG2/adr cells but had no effect in HepG2 cells. Furthermore, cabozantinib did not alter the expression of P-gp mRNA or protein but did stimulate the activity of P-gp ATPase. The docking study indicated that cabozantinib and verapamil may partially share a binding site on P-gp. The reversal concentrations of cabozantinib did not affect the expression of MET, AKT and ERK1/2. Significantly, cabozantinib increased the inhibitory efficacy of doxorubicin in P-gp-overexpressing HepG2/adr cell xenografts in nude mice. CONCLUSION: Cabozantinib reverses P-gp-mediated MDR by directly inhibiting the efflux function of P-gp, indicating that cabozantinib may help to reverse P-gp-mediated MDR in HCC and other cancer chemotherapy.

Laparoscopic common bile duct exploration with primary closure for management of choledocholithiasis: a retrospective analysis and comparison with conventional T-tube drainage.

Laparoscopic common bile duct exploration (LCBDE) had become one of the main options for management of choledocholithiasis. This retrospective comparative study aimed to evaluate on the feasibility and advantages of primary closure versus conventional T-tube drainage of the common bile duct (CBD) after laparoscopic choledochotomy. In this retrospective analysis, 100 patients (47 men and 53 women) with choledocholithiasis who underwent primary closure of the CBD (without T-tube drainage) after LCBDE (Group A) were compared with 92 patients who underwent LCBDE with T-tube drainage (Group B). Both groups were evaluated with regard to biliary complications, hospital stay, and recurrence of stones. The mean operation time was 104.12 minutes for Group A and 108.92 minutes for Group B (P = 0.069). The hospital stay was significantly shorter in Group A than that in Group B (6.95 days and 12.05 days, respectively; P < 0.001). In Group A, bile leakage occurred in two patients on postoperative Day 2 and Day 3, respectively. In Group B, bile leakage noted in one patient after removal of the T-tube on Day 14 after operation (P = 1.000). With a median follow-up time of 40 months for both groups, stone recurrence was noted in two patients in Group A and three patients in Group B (P = 0.672). Primary closure of the CBD is safe and feasible in selected patients after laparoscopic choledochotomy. It results in shorter duration of hospital stay without the need for carrying/care of a T-tube in the postoperative period and similar stone recurrence as that of the conventional method.

Functional distinction of rat liver natural killer cells from spleen natural killer cells under normal and acidic conditions in vitro.

BACKGROUND: The microenvironment within solid tumors has often been shown to exhibit an acidic extracellular pH. Although the morphologic and functional differences in natural killer (NK) cells of the liver and spleen have been reported previously under physiological conditions, the difference under acidic conditions is still unclear. This study was to investigate the differences in the morphological and functional characteristics between rat liver and spleen NK cells under normal and acidic conditions in vitro. METHODS: Liver and spleen NK cells were isolated and purified from Sprague-Dawley rats by density gradient centrifugation and the Dynabeads(®) FlowComp(TM) Flexi system, and stimulated for 4 days with or without IL-2 or treated with low pH or control for different times. Morphology was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cell death and proliferation assays were performed by flow cytometry, IFN-gamma production was tested by ELISA, and cytotoxic activity was evaluated by lactate dehydrogenase (LDH) release assay. RESULTS: Liver NK cells had significantly higher levels of cytotoxic activity than spleen NK cells under normal and acidic conditions, and the maximum difference was observed at pH 5.6. Further analysis revealed that the cytotoxic activity of NK cells was correlated with morphology, cell death, proliferative activity and IFN-gamma production. By TEM, liver NK cells contained a greater number of electron-dense granules per cell at pH 5.6. Moreover, a modest elevation of cell death and reduction of proliferation of liver NK cells occurred within a range of 5.6-7.2. Interestingly, an acidic extracellular pH only marginally, and not significantly, suppressed IFN-gamma production by liver NK cells. CONCLUSION: The sharp morphological and functional differences shown by the two types of NK cells in vitro indicate that liver NK cells are unexpectedly resistant to pH shock.

Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro.

Failure of immune surveillance related to inadequate host antitumor immune responses has been suggested as a possible cause of the high incidence of recurrence and poor overall survival outcome of hepatocellular carcinoma. The stress-induced heat shock proteins (HSPs) are known to act as endogenous "danger signals" that can improve tumor immunogenicity and induce natural killer (NK) cell responses. Exosome is a novel secretory pathway for HSPs. In our experiments, the immune regulatory effect of the HSP-bearing exosomes secreted by human hepatocellular carcinoma cells under stress conditions on NK cells was studied. ELISA results showed that the production of HSP60, HSP70, and HSP90 was up-regulated in both cell lines in a stress-specific manner. After exposure to hepatocellular carcinoma cell-resistant or sensitive anticancer drugs (hereafter referred to as "resistant" or "sensitive" anticancer drug), the membrane microvesicles were actively released by hepatocellular carcinoma cells, differing in their ability to present HSPs on the cell surface, which were characterized as exosomes. Acting as a decoy, the HSP-bearing exosomes efficiently stimulated NK cell cytotoxicity and granzyme B production, up-regulated the expression of inhibitory receptor CD94, and down-regulated the expression of activating receptors CD69, NKG2D, and NKp44. Notably, resistant anticancer drugs enhanced exosome release and generated more exosome-carried HSPs, which augmented the activation of the cytotoxic response. In summary, our findings demonstrated that exosomes derived from resistant anticancer drug-treated HepG2 cells conferred superior immunogenicity in inducing HSP-specific NK cell responses, which provided a clue for finding an efficient vaccine for hepatocellular carcinoma immunotherapy.

Laparoscopic cholecystectomy under epidural anesthesia: a retrospective comparison of 100 patients.

There are limited data about laparoscopic cholecystectomy (LC) under epidural anesthesia. This retrospective comparative study aimed to evaluate on the feasibility and advantages of LC under epidural anesthesia. In this retrospective comparative study, 100 patients (46 men and 54 women) with symptomatic cholelithiasis undergoing laparoscopic cholecystectomy using epidural anesthesia (EA) were compared with 100 patients undergoing laparoscopic cholecystectomy using general anesthesia (GA). Both groups were evaluated with regard to intraoperative mean arterial pressure, heart rate, operation time, duration of stay in the recovery room, and hospital cost. Laparoscopic operation was performed for 200 patients. Mean age of patients was 46.4 ± 6.9 years and 45.3 ± 6.8 years in EA and GA, respectively. Forty-six and 50 per cent of subjects were male in EA and GA, respectively. The mean operation time was 24 minutes and 25.58 minutes for EA and GA, respectively (P = 0.652). The duration of stay in the recovery room was significantly shorter in EA than that in GA (19.56 ± 2.55 minutes vs 56.27 ± 6.85 minutes, respectively; P = 0.0001). In the EA group, 23 patients (23%) had severe shoulder pain during surgery. After receiving pethidine intravenously, all these patients could subsequently undergo surgery smoothly. There were no complications or mortality in either group. Most of the patients regarded EA as a comfortable procedure. The mean hospital cost for the EA group was only three-fourths that of the GA group. LC under EA is feasible and safe in selected patients.

Donor liver natural killer cells alleviate liver allograft acute rejection in rats.

BACKGROUND: Liver enriched natural killer (NK) cells are of high immune activity. However, the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear. METHODS: Ten Gy of whole body gamma-irradiation (WBI) from a 60Co source at 0.6 Gy/min was used for depleting donor-derived leukocytes, and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells, dtlNKs) through portal vein was performed immediately after grafting the irradiated liver. Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients' survival in rat LTx. RESULTS: Transfusion of dtlNKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx, but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat). Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes, better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtlNKs. CONCLUSIONS: Donor liver NK cells alone do not exacerbate liver allograft acute rejection. Conversely, they can alleviate it, and improve the recipients' survival.

Staging systems for predicting survival of patients with hepatocellular carcinoma after surgery.

AIM: To compare the staging systems for stratifying and predicting the prognosis of patients with hepatocellular carcinoma (HCC) after partial hepatectomy (PH). METHODS: Clinical data about 438 HCC patients who underwent PH from January 1991 to December 2004 at our hospital were retrospectively analyzed. Tumor stage was evaluated following the Chinese tumor node metastasis (TNM) and barcelona clinic liver cancer (BCLC) staging systems, respectively. Survival curves for the HCC patients were plotted using the Kaplan-Meier method and differences were compared by the log-rank test. The accuracy of each system for predicting death of HCC patients was evaluated by calculating the area under the receiver operating characteristic curve. RESULTS: The HCC patients were classified into stages I-III, stages I-IV and stages A-C, according to the 3 staging systems, respectively. Log-rank test showed that the cumulative survival rate was significantly different for the HCC patients at 3 Chinese system stages, TNM stages I and II, TNM stages III and IV, and 3 BCLC stages (P < 0.05). However, no significant difference was found in the HCC patients at TNM stages II and III. The accuracy of the Chinese and BCLC staging systems was higher than that of the TNM staging system for predicting the survival rate of HCC patients. CONCLUSION: The Chinese and BCLC staging systems are better for stratifying and predicting the prognosis of HCC patients after PH than the TNM staging system.

Differentiation of embryonic stem cells into hepatocytes that coexpress coagulation factors VIII and IX.

AIM: To establish an efficient culture system to support embryonic stem (ES) cell differentiation into hepatocytes that coexpress F-VIII and F-IX. METHODS: Mouse E14 ES cells were cultured in differentiation medium containing sodium butyrate (SB), basic fibroblast growth factor (bFGF), and/or bone morphogenetic protein 4 (BMP4) to induce the differentiation of endoderm cells and hepatic progenitor cells. Hepatocyte growth factor, oncostatin M, and dexamethasone were then used to induce the maturation of ES cell-derived hepatocytes. The mRNA expression levels of endoderm-specific genes and hepatocyte-specific genes, including the levels of F-VIII and F-IX, were detected by RT-PCR and real-time PCR during various stages of differentiation. Protein expression was examined by immunofluorescence and Western blot. At the final stage of differentiation, flow cytometry was performed to determine the percentage of cells coexpressing F-VIII and F-IX, and ELISA was used to detect the levels of F-VIII and F-IX protein secreted into the culture medium. RESULTS: The expression of endoderm-specific and hepatocyte-specific markers was upregulated to highest level in response to the combination of SB, bFGF, and BMP4. Treatment with the three inducers during hepatic progenitor differentiation significantly enhanced the mRNA and protein levels of F-VIII and F-IX in ES cell-derived hepatocytes. More importantly, F-VIII and F-IX were coexpressed with high efficiency at the final stage of differentiation, and they were also secreted into the culture medium. CONCLUSION: We have established a novel in vitro differentiation protocol for ES-derived hepatocytes that coexpress F-VIII and F-IX that may provide a foundation for stem cell replacement therapy for hemophilia.

Prognostic factors and outcome of 438 Chinese patients with hepatocellular carcinoma underwent partial hepatectomy in a single center.

OBJECTIVE: This study was designed to evaluate the prognostic factors and outcome of 438 Chinese patients with hepatocellular carcinoma who underwent partial hepatectomy in a single center. METHODS: Clinicopathological data of 438 patients with hepatocellular carcinoma who underwent partial hepatectomy at the author's hospital between 1991 and 2004 were reviewed retrospectively. The Kaplan-Meier method was adopted for evaluating survival. Prognostic factors were assessed by Cox proportional hazard model and logistic regression model. RESULTS: The perioperative (30 days) mortality and morbidity were 7.5% (33/438) and 21.7% (95/438), respectively. The operative mortality decreased significantly from 10.6% (23/218) in 1991-2001 to 4.5% (10/220) in 2002-2004 (P = 0.019). Postoperative overall survival rates at 1 year, 3 years, and 5 years were 72.2%, 53.5%, and 43.3%, respectively. Cox multivariate analysis indicated that Child-Pugh score, tumor size, capsular invasion, tumor stage, vascular invasion, and resection margin were independent prognostic factors for overall survival (P < 0.05). Also, 254 cases had tumor recurrence after operation and 87 cases of them were reoperated. Logistic multivariate analysis showed that tumor size, capsular invasion, vascular invasion, lymph node metastasis, extrahepatic metastasis, and resection margin were independent risk factors of tumor recurrence (P < 0.05). CONCLUSIONS: Tumor size, capsular invasion, vascular invasion, and resection margin were the main factors that may impact the overall survival and tumor recurrence. Because resection margin was the only factor that relates to the surgery, enough resection margin (>2 cm) should be obtained whenever possible.

Total laparoscopic liver resection in 78 patients.

AIM: To summarize the clinical experience of laparoscopic hepatectomy at a single center. METHODS: Between November 2003 and March 2009, 78 patients with hepatocellular carcinoma (n = 39), metastatic liver carcinoma (n = 10), and benign liver neoplasms (n = 29) underwent laparoscopic hepatectomy in our unit. A retrospective analysis was done on the clinical outcomes of the 78 patients. RESULTS: The lesions were located in segments I (n = 3), II (n = 16), III (n = 24), IV (n = 11), V (n = 11), VI (n = 9), and VIII (n = 4). The lesion sizes ranged from 0.8 to 15 cm. The number of lesions was three (n = 4), two (n = 8) and one (n = 66) in the study cohort. The surgical procedures included left hemi-hepatectomy (n = 7), left lateral lobectomy (n = 14), segmentectomy (n = 11), local resection (n = 39), and resection of metastatic liver lesions during laparoscopic surgery for rectal cancer (n = 7). Laparoscopic liver resection was successful in all patients, with no conversion to open procedures. Only four patients received blood transfusion (400-800 mL). There were no perioperative complications, such as bleeding and biliary leakage. The liver function of all patients recovered within 1 wk, and no liver failure occurred. CONCLUSION: Laparoscopic hepatectomy is a safe and feasible operation with minimal surgical trauma. It should be performed by a surgeon with sufficient experience in open hepatic resection and who is proficient in laparoscopy.

[Splenic autotransplantation combined with lower esophagus transaction in the treatment of hepatic cirrhosis induced portal hypertension].

OBJECTIVE: To study the therapeutic effect of splenic autotransplantation combined with lower esophagus transaction anastomosis in the treatment of liver cirrhosis induced portal hypertension. METHODS: Thirty-six patients admitted from January 2003 to December 2006 were randomly divided into splenic autotransplantation group undergoing splenic autotransplantation after splenectomy combined with lower esophagus transaction anastomosis, and splenectomy group only undergoing splenectomy combined with lower esophagus transaction anastomosis. The general conduction, splenic scanning, liver function, and the level of serum Tuftsin and IgM of each patient were observed before and after operation. RESULTS: The levels of Tuftsin and IgM in splenic autotransplantation group were significant higher than that of splenectomy group 2 months after the operation, and the liver function showed no significant difference between these two groups. Splenic tissue was detected in the retroperitoneal space by 99mTc-DRBC 2 months after operation. CONCLUSIONS: Splenic autotransplantation combined with lower esophagus transaction anastomosis is a safe and effective treatment strategy for patients with liver cirrhosis induced portal hypertension, and the spleen tissue transplanted into the retroperitoneal space can partially preserve the immune function.

[MicroRNA differential expression profile during differentiation of embryonic stem cells towards hepatocytes induced by sodium butyrate].

OBJECTIVE: To explore the expression profile of microRNAs during the course of embryonic stem cells differentiation towards hepatocytes induced by sodium butyrate. METHODS: Total RNA was extracted from embryonic stem cells on day 0, 6, and 9 during cell differentiation, and microRNA was isolated from the total RNA. Microarray analysis of microRNA expression was performed to detect the different expression levels of microRNA among the indicated time points (day 0, 6, and 9). RESULTS: Compared with the microRNA expression level on day 0 of cell differentiation, 17 different microRNAs exhibited higher expressions both on day 6 and day 9. Twenty-two and 27 microRNA demonstrated lower expressions on day 6 and day 9, respectively. Further analysis revealed that 15 microRNA among the above microRNAs with significant differential expression may keep close interation with histone deacetylase. CONCLUSION: During the course of embryonic stem cells differentiation towards hepatocytes induced by sodium butyrate, histone deacetylase and its relevant microRNAs may play important roles in cell differentiation.

[A survey of bile duct injuries sustained during laparoscopic cholecystectomy].

OBJECTIVE: To summarize the reasons for bile duct injury (BDI) after laparoscopic cholecystectomy (LC), and to determine the effect of multiple treatment after BDI. METHODS: A retrospective cohort study was performed. The medical records of 110 patients diagnosed with BDI after LC from October 1993 to November 2007, in ten large hospitals in Guangdong of China, were reviewed. RESULTS: Among 110 patients with BDI, 58 cases (52.7%) were local patients, whereas 52 cases (47.3%) were transferred from outside hospitals. Reasons for BDI following LC were: (1) Lack of experience of the LC operator (48.2%); (2) LC performed during acute cholecystitis (20.0%); (3) The structure of Calot triangle was unclear (15.5%); (4) Variable anatomical position (11.8%); (5) Intra-operation bleeding (4.5%). The commonest sites of injury were the choledochus and common hepatic duct (76.4%). Following BDI, endoscopic stenting or operative repair was performed in 106 patients. The overall success rate was 95.3% (101/106), with a mortality rate was 0.9% (1/106). Cholangitis occurred in 3.8% (4/106) cases. Choledocho-enterostomy operation was performed in almost 60.0% (63/106) cases, and the success rate was 93.7% (59/63). Endoscopic stenting or operative repair was performed immediately following BDI in 23.6% (25/106) patients, the success rate was 100%; and within 30 days in 63.2% (67/106) patients. Eighty-eight out of 106 patients who underwent repair were successful following the first operative procedure. CONCLUSIONS: Factors such as an un-experienced operator and unclear anatomical position were causes of BDI following LC. Early operative repair should be regarded as the treatment of choice, in patients diagnosed with BDI. Early refer to an experienced hepatobiliary operator ensures a high success rate.

Selective enrichment of hepatocytes from mouse embryonic stem cells with a culture system containing cholestatic serum.

AIM: There is increasing evidence indicating that embryonic stem (ES) cells are capable of differentiating into hepatocyte-like cells in vitro. However, it is necessary to improve the differentiation efficiency so as to promote the clinical application. Here, we report an efficient culture system to support hepatocyte differentiation from ES cells by utilizing cholestatic serum. METHODS: One week after the induction of E14 mouse ES cells into hepatocytes with sodium butyrate, cholestatic serum was added into the culture system at various concentrations and hepatocyte-like cells were induced to proliferate. The morphological and phenotypic markers of hepatocytes were characterized using light microscopy, immunocytochemistry, and RT-PCR, respectively. The function of glycogen storage of the differentiated cells was detected by Periodic acid-Schiff (PAS) reaction, and the ratio of hepatic differentiation was determined by counting the albumin and PAS-positive cells. RESULTS: In the presence of conditional selective medium containing cholestatic serum, numerous epithelial cells resembling hepatocytes were observed. The RT-PCR analysis showed that undifferentiated ES cells did not express any hepatic-specific markers; however, in the presence of sodium butyrate and conditional selective medium containing cholestatic serum, hepatic differentiation markers were detected. Immunofluorescence staining showed that those ES-derived hepatocytes were alpha-fetoprotein, albumin, and cytokeratin 18 positive, with the ability of storing glycogen. Further determination of the hepatic differentiation ratio showed that the application of cholestatic serum efficiently enriched ES-derived hepatocyte-like cells by inducing lineage differentiation and enhancing lineage proliferation. CONCLUSION: The conditional selective medium containing cholestatic serum is optimal to selectively enrich hepatocyte-like cells from mixed differentiated ES cells, which may provide a novel method to improve the hepatic differentiation ratio of ES cells.

[Diagnosis and treatment of primary tumor of small intestine: a report of 58 cases].

OBJECTIVE: To summarize the pathological classification, clinical symptom and experience in the diagnosis and treatment of primary tumor of small intestine. METHODS: Data of 58 patients with primary tumor of small intestine pathologically confirmed from Oct. 1996 to Oct. 2006 were analyzed retrospectively. RESULTS: Thirteen patient (22.4%) had primary benign tumors of small intestine and 45 patient (77.6%) had primary malignant tumors of small intestine. The major clinical signs of primary tumor of small intestine included hemorrhage(85%), abdomen pain(19%), abdomen mass and intestine obstruction(16%). Forty- eight patients (82.8%) were diagnosed by laparotomy of abdominal cavity and misdiagnosed preoperatively as other diseases. CONCLUSIONS: Primary tumors of small intestine are difficult to be diagnosed preoperatively. CT scan, digital subtraction angiography and radionuclide imaging are helpful for the diagnosis. Laparotomy of abdominal cavity is the main choice for those patients with suspicious tumor of small intestine.