Sirolimus increases the anti-cancer effect of Huai Er by regulating hypoxia inducible factor-1α-mediated glycolysis in hepatocellular carcinoma.

BACKGROUND: Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α (HIF-1α) in the immune microenvironment promotes the progression of hepatocellular carcinoma (HCC), leading to enhanced drug resistance in cancer cells. Therefore, altering the immunosuppressive microenvironment by imp-roving the hypoxic state is a new goal in improving cancer treatment. AIM: To analyse the role of HIF-1α, which is closely related to tumour proliferation, invasion, metastasis, and angiogenesis, in the proliferation and invasion of liver cancer, and to explore the HIF-1α pathway-mediated anti-cancer mechanism of sirolimus (SRL) combined with Huai Er. METHODS: Previous studies on HCC tissues identified the importance of HIF-1α, glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) expression. In this study, HepG2 and Huh7 cell lines were treated, under hypoxic and normoxic conditions, with a combination of SRL and Huai Er. The effects on proliferation, invasion, cell cycle, and apoptosis were analysed. Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells. RESULTS: High levels of HIF-1α, LDHA, and GLUT-1 were found in poorly differentiated HCC, with lower patient survival rates. Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment. This was achieved by activation of HIF-1α and glycolysis in HCC, leading to the upregulation of LDHA, GLUT-1, Akt/mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p27. The hypoxia-induced activation of HIF-1α showed the greatest attenuation in the SRL/Huai Er (S50 + H8) group compared to the drug treatments alone (P < 0.001). The S50 + H8 treatment significantly downregulated the expression of mTOR and HIF-1α, and significantly reduced the expression of VEGF mRNA. Meanwhile, the combined blocking of mTOR and HIF-1α enhanced the downregulation of Akt/mTOR, HIF-1α, LDHA, and GLUT-1 mRNA and resulted in the downregulation of PTEN, p27, and VEGF mRNA (P < 0.001). CONCLUSION: SRL increases the anti-cancer effect of Huai Er, which reduces the promotion of hypoxia-induced HIF-1α on the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1α and HIF-1α-PTEN signalling pathways in HCC.

Protein tyrosine phosphatase 1 protects human pancreatic cancer from erastin-induced ferroptosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the lack of early detection method, therapeutic drug and target. We noticed that the expression of Protein Tyrosine Phosphatase Mitochondria1(PTPMT1) is upregulated in PDAC. However, its role in pancreatic cancer remains unknown. METHODS: We first analyzed the expression of PTPMT1 from 50 PDAC patients. Secondly, the survival proportions of different PTPMT1-expressed patients were analyzed. Then, the role and mechanism of PTPMT1 in PDAC were studied by lentivirus transduction system. RESULTS: PTPMT1 was upregulated in PDAC and patients with high PTPMT1 expression displayed lower overall survival rate. Knockdown of PTPMT1 increased the sensitivity to erastin or RSL3 induced ferroptosis. Mechanically, knockdown of PTPMT1 resulted in upregulated Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) and downregulated Solute Carrier Family 7 Member 11 (SLC7A11). In addition, SLC7A11 was upregulated in PDAC tumor tissue and correlated positively with the expression of PTPMT1. However, the expression of ACSL4 was downregulated in PDAC and negatively correlated with the expression of PTPMT1. CONCLUSION: Our study demonstrates that PTPMT1 is upregulated in PDAC and PTPMT1 inhibits ferroptosis by suppressing the expression of ACSL4 and upregulating SLC7A11 in Panc-1 cells, suggesting PTPMT1 might be a potential prognosis biomarker and therapeutic target in PDAC.

PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma.

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan-Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg (r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis (P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

Generation and application of patient-derived xenograft models in pancreatic cancer research.

OBJECTIVE: Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC. DATA SOURCES: The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX. STUDY SELECTION: Original articles and review articles relevant to the review's theme were selected. RESULTS: PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment. CONCLUSIONS: In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

Delayed introduction of immunosuppressive regimens in critically ill patients after liver transplantation.

BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation. We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with ImmuKnow assay. METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities. RESULTS: The median duration of non-immunosuppression was 12 days (range 5-58). Due to the infectious complications, the serial ImmuKnow assay showed a significantly low ATP level of 64±35 ng/mL in the early period after transplantation. With the development of comorbidities, the ImmuKnow value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected. The average ATP level measured just before the development of acute rejection was 271±115 ng/mL. CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial ImmuKnow assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.

Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience.

There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.

[Development of laparoscopic technology in biliary surgery in the past 23 years: a single-center experience].

OBJECTIVE: To summarize the 23-year experience of laparoscopic biliary surgery in General Hospital of PLA and evaluate the application of laparoscopic surgery in the treatment of biliary diseases. METHODS: We retrospectively analyzed the clinical data of 11 419 consecutive patients with biliary diseases undergoing laparoscopic surgery from April, 1992 and December, 2014. The disease spectrum was compared between patients treated before December 31, 2003 and those treated after the time point. RESULTS: The 11419 patients receiving laparoscopic surgery accounted for 56.3% of the total patients undergoing biliary surgeries during the 23 years, including 4701 male and 6718 female patients with a mean age of 50.9∓13.2 years (6-93 years). Most (80.83%) of the patients received laparoscopic surgery for gallbladder stones, and 12.53% patients had the operation for gallbladder polyps. The laparoscopic operation rate was 84.81% in patients with gallbladder stones and 34.91% in patients with extrahepatic bile duct stones, but remained low in patients with biliary carcinoma. In laparoscopic operations, laparoscopic cholecystectomy was the most frequent (96.18%) followed by operations for extrahepatic bile duct stones, in which primary suture accounted for 1.38%, traditional T tube drainage for 0.90% and laparoscopic transcystic duct exploration for 0.72%. For malignant tumors, laparoscopic technique was used mainly for the purpose of exploration (0.34%). The application of laparoscopic technique in biliary surgery tended to increase after the year 2004, especially for benign gallbladder diseases and extrahepatic bile duct stones (P<0.05). CONCLUSION: Laparoscopic technique in biliary surgery is gradually replacing the traditional open operation and becomes the gold standard for the treatment of benign biliary diseases.

[Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors].

OBJECTIVE: To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs. METHODS: We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm). RESULTS: In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups. CONCLUSION: Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.

Clinicopathological characteristics and prognostic factors of intrahepatic biliary cystadenocarcinoma.

BACKGROUND: Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs, but controversy exists regarding the prognosis for IBCAs. This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures. METHODS: Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included. The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC); factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: IBCAs had a strong female predominance, and the most common presenting symptoms were abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older patients, in more male patients, and were associated statistically significant abnormal increase in alanine aminotransferase (P = 0.01) and total bilirubin (P = 0.04). Mural nodules were more frequently seen with IBCAs and may associate with malignancy. It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings. Although complete resection is recommended, enucleation with negative margins also achieved good outcomes. Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive tumor type were independent prognostic factors for overall survival. CONCLUSIONS: It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings. Complete resection is recommended for curative treatment, and patients should be closely followed postoperatively, particularly those with invasive tumors.

[Follow-up studies for long-term postoperative complications of Warshaw operation].

OBJECTIVE: To explore the long-term postoperative complications of Warshaw operation for distal pancreatectomy with preservation of spleen. METHODS: Retrospectively analyzed the clinical data of distal pancreatectomy on 84 cases between January 2006 and January 2012. Among them, 35 patients underwent Warshaw operation for distal pancreatectomy with preservation of spleen and another 23 had distal pancreatectomy with Kimura operation. All of them were followed up. RESULTS: All procedures were successful. There was no perioperative mortality. During the follow-up period, 2 patients undergoing Warshaw operation were lost. The median follow-up period was 2.6 years (range: 0.75-6.75). Twenty-six patients with the recent neuroimaging data showed: 5 patients were diagnosed of splenic infarction and the incidence rate was 19.2% (5/26) and 6 with gastric varices and the incidence rate was 23.1% (6/26). But none of them developed gastrointestinal hemorrhage or splenic abscess. CONCLUSION: The Warshaw operation for distal pancreatectomy with preservation of spleen may increase the risk of long-term postoperative complications so that its operative indication must be strictly mastered.

Technical points of total laparoscopic choledochal cyst excision.

BACKGROUND: Choledochal cyst excision and biliary enteric reconstruction constitute the best therapy for choledochal cyst. And laparoscopy is currently used to cure this disease now. METHODS: We retrospectively analyzed the clinical data of 34 cases of total laparoscopic choledochal cyst excision between January 2007 and August 2011. All patients underwent in vitro Roux-en-Y hepatoenterostomy. RESULTS: All 34 patients underwent successful total laparoscopic choledochal cyst excision. The operation time was 200 - 360 minutes. The duration of hospital stay was 3 - 7 days. Follow-up observations lasted 1 - 56 months. One patient developed an anastomotic stoma stricture, but no other cases had postoperative complications. No patients died. CONCLUSION: Total laparoscopic choledochal cyst excision is safe and feasible.

Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization.

BACKGROUND: This retrospective study was undertaken to analyze the outcome of hepatic resection in fifty-two patients with unresectable hepatocellular carcinoma (HCC) between January 2004 and December 2008. METHODS: Among these fifty-two patients, the mean diameter of the tumor was 7.9 cm (4.4 - 15.5 cm, median 8.5 cm) prior to the first transcatheter arterial chemoembolization (TACE). After 1 - 6 times of TACE (median 2), the median tumor diameter was reduced to 4.2 cm (0 - 8.4 cm) prior to resection. The duration between the last TACE treatment and sequential resection varied from one to six months (median 2.7 months). Serum a-fetoprotein (AFP) levels were abnormal in thirty-eight out of the fifty-two patients. In AFP producing HCCs, AFP levels returned to normal (≤ 400 µg/L) in twenty-five out of thirty-eight patients. Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in forty-five patients, two underwent extended left hemihepatectomy, and one underwent right posterior branch portal vein thrombectomy. One patient received a right hemihepatectomy and three had left hemihepatectomies. RESULTS: Complete tumor radiological response (CR) occurred in five patients (9.6%). There were three cases of perioperative mortality in the fifty-two patients (5.8%). One patient underwent salvaged orthotopic liver transplantation, and twenty-one patients observed tumor recurrence within two years. The 1-, 3- and 5-year survival rates of the fifty-two patients were 77.0% (n = 40), 55.0% (n = 29), and 52.0% (n = 28), respectively. The median survival time after surgery was 49 months (95% confidence interval 7.5 - 52.7 months). CONCLUSIONS: TACE treatment provides a better chance for HCC resection in patients initially diagnosed with unresectable HCC. Furthermore, liver resection should be performed once the tumor is downstaged to be compatible for successful resection.

[Observation of laparoscopic distal pancreatectomy in hepatobiliary surgery: a report of 25 cases].

OBJECTIVE: To explore the clinical application of laparoscopic distal pancreatectomy (LDP) in hepatobiliary operations. METHODS: The clinical data of LDP from 25 cases from June 2008 to December 2011 were retrospectively analyzed. Among them, 9 patients underwent LDP with excision of spleen while another 16 patients had LDP with preservation of spleen. And during the same period, 42 patients undergoing open distal pancreatectomy were selected into the control group. And the patient data of two groups were compared. RESULTS: All of them underwent successfully LDP. Among 16 patients with preservation of spleen, 11 patients undergone the Kimura procedure while another 5 undergone the Warshaw operation. The operative duration was (4.5 ± 1.2) hours, volume of blood loss (256 ± 188) ml, length of incision (4.6 ± 0.9) cm, mean time of oral food taking (1.5 ± 0.9) days and mean postoperative hospital stay (7.1 ± 1.9) days. Pathological examinations showed benign tumor (n = 20), malignant tumor (n = 4) and borderline tumor (n = 1). The mean data of LDP group was significantly less than that of open distal pancreatectomy group in terms of anal exsufflation time, length of incision, postoperative hospital stay time and complication rate, etc. (P < 0.05). Four patients were diagnosed of post-LDP pancreatic fistula (3 A level vs 1 B level) and all of them became cured after conservative treatment. There was no mortality. CONCLUSION: As a safe and feasible procedure, LDP is worthy of wider applications.

Recombinant adenovirus with human indoleamine-2,3-dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells.

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments. METHODS: The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hIDO gene and HBVpreS gene was packaged and amplified in 293 cells. Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hIDO and HBVpreS was detected by RT-PCR and Western blotting respectively. RESULTS: The recombinant adenovirus was produced successfully. Its titer was 2.5 × 10(9) efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells. CONCLUSION: The transfer of hIDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hIDO and HBV preS would provide the experimental basis for future studies.

[Intrahepatic biliary cystadenoma: experience with 10 consecutive cases at a single center].

OBJECTIVE: To summarize the clinical experience with diagnosis and treatment of intrahepatic biliary cystadenoma (IBCA). METHODS: We retrospectively analyzed the data of 10 consecutive IBCA cases treated in our department in light of the characteristics of the epidemiology, radiology, lab tests, pathology and prognostic. RESULTS: The patients are all female with an average age of 48.9 (16-73) years. The number of asymptomatic, slightly symptomatic and severe symptomatic patients was 4, 4 and 2, respectively. Radiological examination showed segmented cystic lesions in all the cases with an average diameter is 13.3∓4.9 cm. The incidence of segmentation, papillary or nodular hyperplasia, and calcification within the lesions was 90%, 60% and 20%, respectively. Macroscopic examination of the specimen showed compartmentation in the lesions, and microscopically, the lesions all showed lining of cubic or columnar epithelium on the inner wall with ovary-like or fibrous stroma. Complete resection of the tumor was achieved in 8 cases and partial resection was performed in 2 cases. The patients were followed up for a mean of 55.3 (12-164) months, and none of the patients with complete tumor resection showed recurrence, while both of the two patients with partial resection had postoperative recurrence. CONCLUSION: IBCA is a rare cystic lesion occurring primarily in middle-aged women. The preoperative diagnosis of this disease relies primarily on radiological evidences, and a complete resection of IBCA may prolong the patient survival.

Efficacy of liver transplantation for acute hepatic failure: a single-center experience.

BACKGROUND: Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate. The outcome of AHF varies with etiology, but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients. This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease. METHODS: A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center. We analyzed and compared the etiology, outcome, prognosis, and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group. RESULTS: AHF was due to viral hepatitis in 25 patients (52.1%; hepatitis B virus in 22), drug or toxic reactions in 14 (29.2%; acetaminophen in 6), Wilson disease in 4 (8.3%), unknown reasons in 3 (6.3%), and miscellaneous conditions in 2 (4.2%). In the LT group, 36 patients (7 underwent living donor LT, and 29 cadaveric LT) had an average model for end-stage liver disease score (MELD) of 35.7. Twenty-eight patients survived with good graft function after a follow-up of 27.3+/-4.5 months. During the waiting time, 6 patients were treated with ALSS and 2 of them died during hospitalization. The 30-day, 12-month, and 18-month survival rates were 77.8%, 72.2%, and 66.7%, respectively. In the N-LT group, 12 patients had an average MELD score of 34.5. Four patients were treated with ALSS and all died during hospitalization. The 90-day and 1-year survival rates were only 16.7% and 8.3%, respectively. CONCLUSIONS: Hepatitis is the most prominent cause of AHF at our center. Most patients with AHF, who fulfill the Kings College Criteria for LT, did not survive longer without LT. ALSS did not improve the prognosis of AHF patients, but may extend the waiting time for a donor. Currently, LT is still the most effective way to improve the prognosis of AHF patients.

[Experience of the treatment following downstaging of larger hepatocellular carcinomas by transcathetheter hepatic arterial chemoembolization in 58 patients].

OBJECTIVE: To evaluate the feasibility of sequential liver resection or liver transplantation following downstaging of larger hepatocellular carcinoma (HCC) by transcatheter arterial chemoembolization (TACE). METHODS: A retrospective study was conducted. And a total of 58 patients with unresectable larger HCC (diameter > 5 cm) from June 2006 to March 2010 underwent TACE. According the outcomes of TACE, they received liver transplantation (LT, n = 36) and liver resection (LR, n = 22) respectively. The overall survival (OS) and recurrence-free survival (RFS) rates were calculated by the Kaplan-Meier method. The multivariate analyses for the influencing factors were evaluated by the Cox proportional hazard model. RESULTS: The median follow-up period of 58 cases was 22 months and the median survival time 23.57 ± 1.54 months. The 1-, 2-, 3-year OS and RFS rates after LT was 94%, 84% & 73% and 88%, 75% & 64% respectively. The median recurrence time was 12.3 ± 6.4 months (range: 3 - 23). Twenty-eight patients had adequate downstaging to qualify for LT under the Milan criteria. The 1-, 2-, 3-year OS and RFS of the downstaging group was better than those of the non-downstaging group (OS: 96%, 88%, 75% vs 92%, 48%, 48% P = 0.067; RFS: 95%, 95%, 79% vs 76%, 40%, 40% P = 0.002). The 1-, 2-, 3-years OS and RFS after LR was 100%, 64% & 52% and 72%, 49% & 49% respectively. The median recurrence time was 9.3 ± 4.5 months (range: 3 - 23). The long-term results of LT group following TACE were better than those of LR group (OS, P = 0.178; RFS, P = 0.139). The multivariate analyses showed that only pathologic total tumor diameter > 7 cm (P = 0.002, RR = 6.578), microvascular invasion (P = 0.001, RR = 5.737) and poor differentiation (P = 0.048, RR = 4.335) were significantly correlated with tumor recurrence. CONCLUSION: Sequential liver resection and liver transplantation after downstaging by TACE are feasible for some larger HCCs. And the long-term prognosis is satisfactory.

Diagnosis and treatment of fungal infection after liver transplantation.

BACKGROUND: Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient's health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation. METHODS: Clinical data for 232 liver transplant patients at risk of fungal infection were examined for the presence of fungus in the blood, fluid, sputum, urine and stools of patients and by chest or abdominal CT scans. Patients diagnosed with a fungal infection were treated with Fluconazole or, if this was not effective, Voriconazole or Amphotericin B. Immunosuppressive therapy was also reviewed. RESULTS: Thirty-seven of 232 (15.9%) patients were diagnosed with a fungal infection, which occurred 4 to 34 days post-transplantation. Candida infections were diagnosed in 23 cases (62.2%) and Aspergillus infections in 12 cases (32.4%). Twenty-one cases were effectively treated with Fluconazole, 11 cases with Voriconazole, and two cases with Amphotericin B; however, three cases were not effectively treated with any of the antifungal agents. Overall, treatment was effective in 91.9% of patients. CONCLUSIONS: Fungal infection has a significant influence on survival rate after liver transplantation. Imaging studies, and pathogenic and biopsy examinations can diagnose fungal infections, which can be effectively treated with antifungal agents such as Fluconazole, Voriconazole or Amphotericin B.

Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation.

BACKGROUND: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria. METHODS: We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded. RESULTS: Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29+/-1.63 months. Six patients died of tumor recurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant. CONCLUSIONS: Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

[Causes and management of ischemic-type biliary lesion after orthotopic liver transplantation].

OBJECTIVE: To discuss the causes, diagnosis, prophylaxis and treatment of ischemic-type biliary lesions (ITBLs) following orthotopic liver transplantation (OLT). METHODS: A retrospective analysis was performed for 326 OLT patients from January 2002 to January 2009. The post-OLT etiological factors and treatment of ITBL cases were analyzed. RESULTS: ITBL occurred in 23 patients (7.05%). It included intrahepatic biliary lesions (n=9), extrahepatic lesions (n=12) and diffuse extrahepatic and intrahepatic biliary lesions (n=2). Through a COX regression, the risk factors were independently associated with ITBL serious hepatitis as the primary disease (RR: 3.204; P=0.014) and cold donor ischemic time beyond 11.5 hours (RR: 4.895; P=0.000). All ITBL patients underwent drug therapy, endoscopy (n=10), operation (n=6) or re-OLT (n=7). And improvement was found in 17 patients. CONCLUSION: Avoiding too long old ischemic time of donor liver and carefully evaluating the indications of recipients are effective preventive measures of ITBL. It is crucial to select a proper treatment according to the conditions of each individual patient.