The net parenchymal thickness predicts pancreatic fistula after pancreaticoduodenectomy: a retrospective cohort study of objective data.

BACKGROUND: The clinically relevant postoperative pancreatic fistula (CR-POPF) is still a challenging complication of pancreaticoduodenectomy (PD). This study aims to explore the predictors of CR-POPF after PD, including net parenchymal thickness (NPT) of pancreatic neck. METHODS: The consecutive patients who underwent PD at a tertiary hospital were retrospectively reviewed. Univariate and multivariate analyses were conducted on the perioperative data, which was mainly extracted from the objective data, containing the results from the laboratory tests and the imaging examination. NPT refers to the total thickness of pancreatic gland excluding main pancreatic duct (MPD) at the CT film. RESULTS: Univariate analyses showed that total serum bilirubin (TBiL) and albumin (ALB) levels, MPD size and NPT were significantly different between the patients with and without CR-POPF. The white blood cell count, the rate of intra-abdominal infection (IAI) and the postoperative length of hospital stay (LOS) were associated with the incidence of CR-POPF. The proportion of patients with pancreatic adenocarcinoma or chronic pancreatitis was significantly lower in the CR-POPF group than in the non-CR-POPF group. Multivariate analyses manifested that ALB ≤35 g/L and NPT >10 mm were two of the independent risk factors for CR-POPF. CONCLUSION: Preoperative ALB ≤35 g/L and NPT > 10 mm were both the independent predictors of CR-POPF. CR-POPF was associated with the higher IAI rate and the extended LOS.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Downregulation of orosomucoid 2 acts as a prognostic factor associated with cancer-promoting pathways in liver cancer.

BACKGROUND: Liver cancer has a high mortality and morbidity rate throughout the world. In clinical practice, the prognosis of liver cancer patients is poor, and the complex reasons contribute to treatment failures, including fibrosis, hepatitis viral infection, drug resistance and metastasis. Thus, screening novel prognostic biomarkers is of great importance for guiding liver cancer therapy. Orosomucoid genes (ORMs) encode acute phase plasma proteins, including orosomucoid 1 (ORM1) and ORM2. Previous studies showed their upregulation upon inflammation, but the specific function of ORMs has not yet been determined, especially in the development of liver cancer. AIM: To determine the expression of ORMs and their potential function in liver cancer. METHODS: Analysis of the expression of ORMs in different human tissues was performed on data from the HPA RNA-seq normal tissues project. The expression ratio of ORMs was determined using the HCCDB database, including the ratio between liver cancer and other cancers, normal liver and other normal tissues, liver cancer and adjacent normal liver tissues. Analysis of ORM expression in different cancer types was performed using The Cancer Genome Atlas and TIMER database. The expression of ORMs in liver tumor tissues and adjacent normal tissues were further confirmed using Gene Expression Omnibus data, including GSE36376 and GSE14520. The 10-year overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS) rates between high and low ORM expression groups in liver cancer patients were determined using the Kaplan-Meier plotter tool. Gene Set Enrichment Analysis (GSEA) was employed to explore the ORM2-associated signaling network. Correlations between ORM2 expression and tumor purity or the infiltration level of macrophages in liver tumor tissues were determined using the TIMER database. The correlation between ORM2 gene levels, tumor-associated macrophage (TAM) markers (including CD68 and TGFß1) and T cell immunosuppression (including CTLA4 and PD-1) in liver tumor tissues and liver GTEx was determined using the GEPIA database. RESULTS: ORM1 and ORM2 were highly expressed in normal liver and liver tumor tissues. ORM1 and ORM2 expression was significantly decreased in liver tumor tissues compared with adjacent normal tissues, and similar results were also noted in cholangiocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma. Further analysis of the Gene Expression Omnibus Database also confirmed the downregulation of ORM1 and ORM2 in liver tumors. Survival analysis showed that the high ORM2 group had better survival rates in OS, PFS and RFS. ORM1 only represented better performance in PFS, but not in OS or RFS. GSEA analysis of ORM2 from The Cancer Genome Atlas liver cancer data identified that ORM2 positively associated with the G2/M checkpoint, E2F target signaling, as well as Wnt/ß-catenin and Hedgehog signaling. Moreover, apoptosis, IFN-α responses, IFN-γ responses and humoral immune responses were upregulated in the ORM2 high group. ORM2 expression was negatively correlated with the macrophage infiltration level, CD68, TGFß1, CTLA4 and PD-1 levels. CONCLUSION: The results showed that ORM1 and ORM2 were highly expressed specifically in liver tissues, whereas ORM1 and ORM2 were downregulated in liver tumor tissues. ORM2 is a better prognostic factor for liver cancer. Furthermore, ORM2 is closely associated with cancer-promoting pathways.

Do patients benefit more from robot assisted approach than conventional laparoscopic distal pancreatectomy? A meta-analysis of perioperative and economic outcomes.

BACKGROUND/PURPOSE: Robotic approach has improved the ergonomics of conventional laparoscopic distal pancreatectomy (LDP), but whether patients benefit more from robot assisted distal pancreatectomy (RADP) is still controversial. This meta-analysis aims to compare the perioperative and economic outcomes of RADP with LDP. METHODS: A systematic review of the literature was carried out on PubMed, EMBASE, and the Cochrane Library between January 1990 and March 2017. All eligible studies comparing RADP versus LDP were included. Perioperative and economic outcomes constituted the end points. RESULTS: 13 English studies with 1396 patients were included. Regarding to intraoperative outcomes, RADP was associated with a significant decrease in conversion rate (OR = 0.52; 95%CI: 0.34, 0.78; P = 0.002). Although the spleen-preserving rates were comparable between RADP and LDP, a significant higher splenic vessels conservation rate was observed in the RADP group (OR = 4.71; 95%CI: 1.77, 12.56; P = 0.002). No statistically significant differences were found at operation time, estimated blood loss and blood transfusion rate. Concerning postoperative outcomes, pooled data indicated the overall morbidity, pancreatic fistula and the length of hospital stay did not differ significantly between the RADP and LDP groups. And concerning pathological outcomes, positive margin rate and the number of lymph nodules harvested were comparable between the two groups. The operative cost of RADP was almost double that of LDP (WMD = 2350.2 US dollars; 95%CI: 1165.62, 3534.78; P = 0.0001). CONCLUSION: RADP showed a slight technical advantage. But whether this benefit is worth twofold cost should be considered by patient's individuation.

Combination of serum tumor markers dickkopf-1, DCP and AFP for the diagnosis of primary hepatocellular carcinoma.

OBJECTIVE: To evaluate the detection accuracy of the biomarkers dickkopf-1, DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers. METHODS: The study was composed of three groups, one with HCC patients, one with non-HCC liver diseases and one with healthy controls. Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA. The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel. RESULTS: The HCC group showed higher levels of dickkopf-1, DCP and AFP than the other two groups (P < 0.05). Dickkopf-1 showed better sensitivity (73.26% vs. 58.13%, P < 0.05) and better specificity (44.0% vs. 29.0%, P < 0.05) than AFP. DCP also had better sensitivity (74.42% vs. 58.13%, P < 0.05) than AFP, but their specificity was similar (30.00% vs. 29.00%, P > 0.05). The combination of the biomarkers as a serum panel produced much better sensitivity (93.02%) and specificity (78.00%) than each of the markers individually (P < 0.05). CONCLUSION: The combination of AFP, DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone. The tests are convenient and inexpensive, and may serve as a valuable addition to current options for the diagnosis of HCC.

Hepatectomy with primary closure of common bile duct for hepatolithiasis combined with choledocholithiasis.

AIM: To evaluate the feasibility of hepatectomy and primary closure of common bile duct for intrahepatic and extrahepatic calculi. METHODS: From January 2008 to May 2013, anatomic hepatectomy followed by biliary tract exploration without biliary drainage (non-drainage group) was performed in 43 patients with intrahepatic and extrahepatic calculi. After hepatectomy, flexible choledochoscopy was used to extract residual stones and observe the intrahepatic bile duct and common bile duct (CBD) for determination of biliary stricture and dilatation. Function of the sphincter of Oddi was determined by manometry of the CBD. Primary closure of the CBD without T-tube drainage or bilioenteric anastomosis was performed when there was no biliary stricture or sphincter of Oddi dysfunction. Dexamethasone and anisodamine were intravenously injected 2-3 d after surgery to prevent postoperative retrograde infection due to intraoperative bile duct irrigation, and to maintain relaxation of the sphincter of Oddi, respectively. During the same period, anatomic hepatectomy followed by biliary tract exploration with biliary drainage (drainage group) was performed in 48 patients as the control group. Postoperative complications and hospital stay were compared between the two groups. RESULTS: There was no operative mortality in either group of patients. Compared to intrahepatic and extrabiliary drainage, hepatectomy with primary closure of the CBD (non-drainage) did not increase the incidence of complications, including residual stones, bile leakage, pancreatitis and cholangitis (P > 0.05). Postoperative hospital stay and costs were nevertheless significantly less in the non-drainage group than in the drainage group. The median postoperative hospital stay was shorter in the non-drainage group than in the drainage group (11.2 ± 2.8 d vs 15.4 ± 2.1 d, P = 0.000). The average postoperative cost of treatment was lower in the non-drainage group than in the drainage group (29325.6 ± 5668.2 yuan vs 32933.3 ± 6235.1 yuan, P = 0.005). CONCLUSION: Hepatectomy followed by choledochoendoscopic stone extraction without biliary drainage is a safe and effective treatment of hepatolithiasis combined with choledocholithiasis.

Pancreaticojejunostomy, hepaticojejunostomy and double Roux-en-Y digestive tract reconstruction for benign pancreatic diseases.

Surgery such as digestive tract reconstruction is usually required for pancreatic trauma and severe pancreatitis as well as malignant pancreatic lesions. The most common digestive tract reconstruction techniques (e.g., Child's type reconstruction) for neoplastic diseases of the pancreatic head often encompass pancreaticojejunostomy, choledochojejunostomy and then gastrojejunostomy with pancreaticoduodenectomy, whereas these techniques may not be applicable in benign pancreatic diseases due to an integrated stomach and duodenum in these patients. In benign pancreatic diseases, the aforementioned reconstruction will not only increase the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the risks of traction, twisting and angularity of the jejunal loop. In addition, postoperative complications such as mixed fistula are refractory and life-threatening after common reconstruction procedures. We here introduce a novel pancreaticojejunostomy, hepaticojejunostomy and double Roux-en-Y digestive tract reconstruction in two cases of benign pancreatic disease, thus decreasing not only the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the possibility of postoperative complications compared to common reconstruction methods. Postoperatively, the recovery of these patients was uneventful and complications such as bile leakage, pancreatic leakage and digestive tract obstruction were not observed during the follow-up period.

Anatomic resection of liver segments 6-8 for hepatocellular carcinoma.

AIM: To report the devised anatomic liver resection of segments 6, 7 and 8 to improve the resection rate for patients with right liver tumors. METHODS: We performed anatomic liver resection of segments 6, 7 and 8 to guarantee the maximum preservation of the remaining normal liver tissue. Segment 5 was determined by two steps of Glissonean pedicle occlusion. And a "┏┛" shaped broken resection line was marked upon the diaphragmatic surface of the liver. Selective right hemihepatic inflow occlusion was used to reduce blood loss during parenchymal transection between segments 6 and 5 and between segments 8 and 5. If needed, total hepatic Glissonean pedicle occlusion was used during parenchymal transection between segment 8 and the left liver. RESULTS: Compared to right hemihepatectomy, the percentage of future liver remnant volume was increased by an average of 13.9% if resection of segments 6, 7 and 8 was performed. Resection of segments 6, 7 and 8 was completed uneventfully. After hepatectomy, the inflow and outflow of segment 5 were maintained. There was no perioperative mortality, postoperative abdominal bleeding or bile leakage in this group. Alpha-fetoprotein (AFP) returned to the normal range within 2 mo after the operation in all the patients. One patient died 383 d postoperatively due to obstructive suppurative cholangitis. One patient suffered from severe liver dysfunction shortly after surgery and had intrahepatic recurrence 4 mo postoperatively. Postoperative lung metastasis was found in one patient. No tumor recurrence was found in the other patients and the parameters including liver function and AFP level were in the normal range. CONCLUSION: Anatomic liver resection of segments 6, 7 and 8 can be a conventional operation to improve the overall resection rate for hepatocellular carcinoma.

Coagulase-negative staphylococcus and enterococcus as predominant pathogens in liver transplant recipients with Gram-positive coccal bacteremia.

BACKGROUND: Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT. METHODS: A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients. RESULTS: In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month. The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates), methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades II - IV (P = 0.013, OR: 16.253, 95%CI: 1.822 - 144.995), pre-LT use of empirical antibiotics (P = 0.018, OR: 1.029, 95%CI: 1.002 - 1.057), post-LT urinary tract infections (P < 0.001, OR: 20.340, 95%CI: 4.135 - 100.048) and abdominal infection (P = 0.004, OR: 2.820, 95%CI: 1.122 - 10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli. CONCLUSIONS: Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.

Risk factors for pneumonia caused by multidrug-resistant Gram-negative bacilli among liver recipients.

Pneumonia caused by multidrug-resistant (MDR) Gram-negative bacilli is associated with a higher mortality rate. The appropriate empiric therapy is based on the understanding of local etiology and MDR pattern. This study was to evaluate the spectrum of Gram-negative bacilli, MDR rate, risk factors and mortality in 475 liver transplantation (LT) recipients. In the first six months after LT, the incidence of bacterial pneumonia was 21.3% (101/475). The overall infectious incidence during the first post-transplant month was 80.2%. The most frequent pneumonia isolates were Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. Gram-negative bacilli accounted for 69.6% of all pneumonia pathogens. Of the main 124 Gram-negative bacilli isolates, MDR rate was 58.9%. Four risk factors for post-LT pneumonia caused by MDR Gram-negative bacilli were LT candidates with grade II-IV encephalopathy (OR 2.275, 95%CI 1.249-4.124, p = 0.006), prolonged duration of endotracheal intubation (OR 8.224, 95%CI 4.276-15.815, p = 0.013), tracheostomy (OR 4.929, 95%CI 1.099-18.308, p = 0.027) and post-LT episode(s) of reoperations (OR 10.597, 95%CI 3.726-30.134, p < 0.001). MDR Gram-negative bacterial pneumonia-related mortality was significantly higher than that because of antibiotic-susceptible bacilli (45.6% vs. 11.4%, p = 0.010). Our data suggest that pneumonia caused by MDR Gram-negative bacilli after LT is common, and associated with the severity of underlying disease, prolonged mechanical ventilation and upper abdominal surgery.

Spectrum and risk factors for invasive candidiasis and non-Candida fungal infections after liver transplantation.

BACKGROUND: Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients. The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients. The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients. METHODS: A retrospective analysis was made of recorded data on the epidemiology, risk factors, and mortality of invasive fungal infections in 352 liver transplant recipients. RESULTS: Forty-two (11.9%) patients suffered from invasive fungal infection. Candida species infections (53.3%) were the most common, followed by Aspergillus species (40.0%). There were 21 patients with a superficial fungal infection. The median time to onset of first invasive fungal infection was 13 days, first invasive Candida infection 9 days, and first invasive Aspergillus infection 21 days. Fifteen deaths were related to invasive fungal infection, 10 to Aspergillus infection, and 5 to Candida infection. Invasive Candida species infections were associated with encephalopathy (P = 0.009) and postoperative bacterial infection (P = 0.0003) as demonstrated by multivariate analysis. Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy (P = 0.004), renal dysfunction (P = 0.005) and hemodialysis (P = 0.001). CONCLUSIONS: The leading etiologic species of invasive fungal infections are Candida and Aspergillus, which frequently occur in the first posttransplant month. Encephalopathy and postoperative bacterial infection predispose to invasive Candida infection. Posttransplant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection. More studies are needed to determine the effect of prophylactic antifungal therapy in high risk patients.

Efficacy of hepatitis B immunoglobulin in relation to the gene polymorphisms of human leukocyte Fcgamma receptor III (CD16) in Chinese liver transplant patients.

BACKGROUND: Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients. METHODS: Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. RESULTS: Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5%) subjects, whereas TG in 31 (40.3%) and GG in 11 (14.3%). In the 559G carrier group (n = 42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n = 35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P < 0.05). CONCLUSIONS: A single nucleotide polymorphism (T/G) at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG administration.

[Reduction of endotoxin may protect lung from injury in rats with hepatopulmonary syndrome].

OBJECTIVE: To study the protective effects of ofloxacin by reduction of endotoxin on lung in rats with hepatopulmonary syndrome (HPS). METHODS: Rat models of HPS were induced by ligating the bile duct to result in the biliary cirrhosis. Thirty male SD rats were randomly divided into three groups with 10 animals in each one: sham operation group (the bile ducts were isolated and 2 ml NS was injected i.p), HPS model group (the bile ducts were ligated and 2 ml NS was injected i.p) and levofloxacin group (the bile ducts were did as the former group and 20 mg/kg ofloxacin injected i.p). After 6 weeks the portal pressure, ratios of dry weight to wet weight of lung (D/W), weight of spleen, plasma levels of endotoxin, MPO active and MDA contents in the lung. Plasma and lavage fluid of lung were examined. The results of the blood-gas analysis, the bacterial culture of blood, bile and ascites and the evaluation of pathologic change of lung be also investigated. RESULTS: In levofloxacin group, portal pressure [(19.28 +/- 2.3) compare with (17.80 +/- 2.18)cm H2O, P<0.01], D/W [(5.1 +/- 0.7) compare with (4.9 +/- 0.7), P <0.01], plasma endotoxin levels [(59 +/- 6.2) compare with (268 +/- 35.6)ng/L, P<0.01], MPO active [(0.40 +/- 0.10) compare with (0.24 +/- 0.03)U, P<0.01] and MDA [(0.32 +/- 0.05) compare with (0.22 +/- 0.03) micromol/L, P<0.01] contents in the lung were significantly decreased compared with those in HPS group, and the inflammation of lung was also obviously alleviated. CONCLUSION: Reduction of endotoxin can attenuate the injury of lung in HPS rats.

Increased expression of non-interleukin-2 T cell growth factors and their implications during liver allograft rejection in rats.

BACKGROUND AND AIM: Rejection remains a problem in the transplantation field. The aim of this study was to establish acute and chronic rejection models in rats and to investigate the roles of non-interleukin (IL)-2 T cell growth factors such as IL-15, IL-7 and IL-13 during rejection. METHODS: A liver transplant model was established using Dark Agouti and Brown Norway rats. The rats were divided into group A, left without treatment; group B, received cyclosporinee (1 mg/kg/day); and group C, cyclosporinee (4 mg/kg/day). Histopathological, reverse transcriptase-polymerase chain reaction and western blot were performed in liver specimens obtained from different time-points after transplantation in the three groups. RESULTS: In group A, the livers showed irreversible acute cellular rejection with cell infiltration. In group B, chronic liver rejection was found, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy and liver fibrosis. No apparent histological alterations were observed in group C. IL-15, IL-7 and IL-13 messenger RNA and their protein were all highly expressed in the liver specimens of groups A and B. Upregulated expression was found in IL-15 since the first day after transplantation and in IL-7 and IL-13 since day 6. The extent of IL-15 upregulation was more than that of IL-7 and IL-13. CONCLUSIONS: Liver transplantation in Dark Agouti to Brown Norway rats with low-dose immunosuppression can induce chronic rejection. In the process of acute and chronic allograft rejections, non-IL-2 T cell growth factors such as IL-15, IL-7 and IL-13 play roles. Strategies should pay more attention to regulating these cytokines after liver transplantation.

Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation.

OBJECTIVE: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. METHODS: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-gamma level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). RESULTS: No signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9-15) d posttransplantation with a median survival time of (10.7+/-0.5) d and (11.2+/-2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-gamma in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. CONCLUSION: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.