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BACKGROUND: Liver transplantation is so far the most effective therapeutic modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury represents a critical barrier to liver transplantation. Primary graft dysfunction and small-for-size syndrome are closely associated with I/R injury. Ischemic preconditioning (IPC) is defined as a brief period of liver ischemia followed by reperfusion, and has demonstrated protections against a prolonged I/R injury and improved the capacity of regeneration. The article aimed to review IPC literatures for the understanding of the effects of IPC on I/R injury involving in the procurement of donor liver and protective mechanisms. DATA SOURCES: A literature search of MEDLINE and Web of Science databases using "liver transplantation", "liver regeneration", "hepatectomy", "ischemia/reperfusion" and "ischemic preconditioning" was performed, and then a large amount of related data was collected. RESULTS: The literature search provided a huge amount of evidence for the protective effects of IPC on I/R injury in liver transplantation, including reduction of blood loss in hepatectomy, intraoperative hemodynamic stability and its significant role in liver regeneration. The mechanism involves in balancing inflammatory cytokines, enhancing energy status and mitigating microcirculatory disturbance. CONCLUSION: IPC plays an essential role in hepatectomy before and after harvest of living donor liver and implantation of liver graft.
BACKGROUND: The pathogenesis of hepatopulmonary syndrome is complicated and remains unknown. This review aims to provide an updated knowledge about the pathogenesis of the syndrome. DATA SOURCES: Five medical databases, MEDLINE, Science-Direct, OVID, Springer Link, and Wiley InterScience were searched for articles on "hepatopulmonary syndrome", "cirrhosis", "angiogenesis", "intestinal endotoxemia", "nitric oxide", "carbon monoxide", and other related subjects. RESULTS: Currently, imbalance between vasodilation and vasoconstriction, intestinal bacterial translocation, intestinal endotoxemia, and activation of the lung monocyte/macrophage system may play important roles in the pathogenesis of hepatopulmonary syndrome. Recent studies found that angiogenesis is also an important factor in the pathogenesis of experimental hepatopulmonary syndrome. CONCLUSION: Angiogenesis inhibition may be a potential approach for the treatment of hepatopulmonary syndrome in the future.
BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.
BACKGROUND: Liver transplantation (LT) has been widely accepted as the treatment of choice for end-stage liver diseases. Due to the scarcity of cadaveric donors, adult-to-adult living donor liver transplantation (LDLT) is advocated as a practical alternative to deceased donor liver transplantation (DDLT). However, some reports suggest that the long-term and recurrence-free survival rates of LDLT are poorer than those of DDLT for hepatocellular carcinoma (HCC). This study aimed to compare the long-term and recurrence-free survival rates of HCC between LDLT and DDLT. METHODS: We retrospectively analyzed the clinical data of 150 patients with HCC from January 2005 to March 2009. Eleven patients who died of complications during the perioperative period were excluded. The remaining 139 eligible patients (101 DDLT and 38 LDLT) were regularly followed up to October 2009. The Chi-square test or Fisher s exact test were used to compare the characteristics of LDLT and DDLT. The long-term and recurrence-free survival curves of both groups were determined using the Kaplan-Meier method with comparisons performed using the log-rank test. One-way analysis of variance was performed to compare the waiting time of the two groups. RESULTS: Survival rates at 1, 2, 3, and 4 years for LDLT were 81%, 62%, 53%, and 45% and for DDLT were 86%, 60%, 50%, and 38%, respectively. The overall 1-, 2-, 3-, and 4-year recurrence-free rates for LDLT were 71%, 49%, 42%, and 38%, and for DDLT were 76%, 52%, 41%, and 37%, respectively. No significant differences were found by the log-rank test on both long-term and recurrence-free survival rates. CONCLUSIONS: The role of LDLT is reinforced by our study. It may expand the donor pool and achieve the same long-term and recurrence-free survival rates of DDLT.
BACKGROUND: At present, imaging is used not only to show the form of images, but also to make three-dimensional (3D) reconstructions and visual simulations based on original data to guide clinical surgery. This study aimed to assess the use of a medical image-processing system in liver transplantation surgery. METHODS: The data of abdominal 64-slice spiral CT scan were collected from 200 healthy volunteers and 37 liver cancer patients in terms of hepatic arterial phase, portal phase, and hepatic venous phase. A 3D model of abdominal blood vessels including the abdominal aorta system, portal vein system, and inferior vena cava system was reconstructed by an abdominal image processing system to identify vascular variations. Then, a 3D model of the liver was reconstructed in terms of hepatic segmentation and liver volume was calculated. The FreeForm modeling system with a PHANTOM force feedback device was used to simulate the real liver transplantation environment, in which the total process of liver transplantation was completed. RESULTS: The reconstructed model of the abdominal blood vessels and the liver was clearly demonstrated to be three-dimensionally consistent with the anatomy of the liver, in which the variations of abdominal blood vessels were identified and liver segmentation was performed digitally. In the model, liver transplantation was simulated subsequently, and different modus operandi were selected successfully. CONCLUSION: The digitized medical image processing system may be valuable for liver transplantation.
BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4+ T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4+ T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4+ T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4+ T cells. METHODS: We separated and purified CD4+ T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). We then assessed CD4+ T cell survival and proliferation and the expression of NF-κB and AP-1. RESULTS: Activated CD4+ T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4+ T cells, whereas MP reduced the survival of activated CD4+ T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-κB essential modifier-binding domain (NBD) inhibited the survival of activated CD4+ T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-κB induced by poly I:C and CpG DNA in activated CD4+ T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4+ T cells was not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4+ T cells is promoted by TLR ligands, but this effect is inhibited by MP.
BACKGROUND: Local cryoablation guided by CT or ultrasound has been widely applied in the treatment of hepatocellular carcinoma. However, it is still difficult to apply this technique in certain regions such as the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. This study aimed to evaluate the safety and efficacy of using magnetic resonance imaging (MRI)-guided percutaneous cryoablation as well as the effect of using an open MRI system in guiding and monitoring the treatment of hepatocellular carcinoma in these regions. METHODS: Cryoablation, guided by an open 0.35T MRI scanner and with the assistance of an MRI-compatible optical navigation system, was performed on 32 patients with hepatocellular carcinoma at the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. Each patient had one or two tumors. The total number of tumors treated was 36. The tumor diameters ranged from 2.5 to 10.0 cm (mean 4.7±1.8 cm). The cryosurgical system was MRI-compatible and equipped with cryoprobes 1.47 mm in outside diameter. Under the guidance of MRI in combination with the optical navigation system, the cryoprobes were introduced percutaneously into a tumor at the planned targeting points while critical organs or tissues were avoided. Each cryoablation procedure included two freezing-thawing cycles, and MRI images were acquired dynamically to monitor the ablation of the tumor from time to time during the operation. In order to investigate the therapeutic effects of a cryoablation procedure, AFP measurements and liver-enhanced MRI or CT-enhanced scans were performed at regular times. RESULTS: MRI and optical navigation system-guided cryoablation procedures were successfully performed on all 32 patients (36 tumor sites) and no serious complications occurred. The follow-up period ranged from 5 to 12 months. The 6- and 12-month overall survival rates were 96.8% and 90.6%, respectively. According to the diagnosis of liver-enhanced MRI scans, 10 patients (31.3%) had complete ablation, 18 (56.3%) partial ablation (>80%), 3 (9.4%) stable disease (>50% ablation), and 1 (3.1%) progressive disease (a new tumor site in the liver). The overall efficacy was 87.5%. CONCLUSIONS: MR-guided percutaneous cryoablation using optical navigation is a safe and effective minimally invasive procedure for the treatment of hepatocellular carcinoma at certain special regions, which is difficult to treat with other imaging guidance approaches. With its unique and superb imaging functions, MRI plays an important role in the display, guidance, and monitoring of the cryoablation procedure in treating hepatocellular carcinoma at these special regions. Equipped with an MRI-compatible optical navigation system, MRI-guided therapy makes the cryoablation procedure more precise and safe.
BACKGROUND: Health care workers (HCWs) constitute a high-risk population of HBV infection. There are limited data on the efficacy of vaccination in HCWs in India. This study was to evaluate the efficacy of indigenous recombinant hepatitis B vaccine, Shanvac-B, in HCWs. METHODS: In 597 HCWs screened before the vaccination, 216 (36.2%) showed the presence of at least one of the markers of HBV/HCV infection. Of the remaining 381 (63.8%) HCWs who were considered for vaccination, only 153 (age 18-45 years; 48 males and 105 females) were available for final assessment. These HCWs received 20 µg of vaccine at 0, 1 and 6 months. They were asked for the reactogenicity and monitored for the seroprotective efficacy of the vaccination. Anti-HBs titres were measured after vaccination at 1, 2 and 7 months. The presence of anti-HBs titers equal to 1 MIU/ml was considered as seroconversion and that of titres greater than 10 MIU/ml as seroprotection. RESULTS: After vaccination, 32 males (67%) and 76 females (72%) showed seroconvertion; finally 12 (25%) of the males and 47 (45%) of the females were seroprotected. Seroprotection at 2 and 7 months was more dominant in the females than in the males (96% vs. 56%, P=0.001, 100% vs. 85%, P=0.0001), respectively. Geometric mean titres of anti-HBs after vaccination were also higher in the females than in the males (257±19.7 vs. 29±1.88 MIU/ml, P=0.01, 1802±35.2 vs. 306±13.6 MIU/ml, P≤0.05, 6465±72 vs. 2142±73.6 MIU/ml, P<0.05). Seven male HCWs showed unsatisfactory response, non-response (n=3, 6%) and hypo-response (≤10 MIU/ml, n=4, 8%) at the end of vaccination. Smoking and alcoholism were significantly correlated with unsatisfactory response. No significant adverse effects of vaccination were observed in any HCW. CONCLUSIONS: The presence of HBsAg in HCWs indicates that a high proportion of HCWs are infected with HBV and HCV in India. Recombinant indigenous vaccine Shanvac-B is highly efficacious in HCWs, and its immunogenicity is significantly higher in females than in males. However, pre-vaccination screening of HCWs is strongly recommended in India.
BACKGROUND: Data on the prevalence of hepatitis C in patients with inflammatory bowel diseases (IBD) are limited and conflicting. This study was to assess the prevalence of hepatitis C virus (HCV) infection in IBD patients and to define the clinical and immunologic profile of IBD associated with HCV infection. METHODS: Ten patients (seven females and three males) with IBD and HCV infection were consecutively recruited in our department between June 2005 and May 2010. We analyzed the clinical and serologic description of all patients. RESULTS: The mean age of the 10 patients was 41 years and the median disease duration was 7 years. With present and/or past HCV infection, the patients had clinical manifestations and were positive for endoscopic study or histological test. Compared with the HCV-negative IBD group, the HCV-positive IBD group have a higher positive rate of autoantibodies (antinuclear antibodies, antieutrophil cytoplasmic antibody, and anti-SSa/SSb). In the HCV-positive group, 8 patients were positive for p-antieutrophil cytoplasmic antibody, 4 positive for antinuclear antibodies, and 3 positive for anti-SSa/SSb. Four patients had an elevated level of transaminase (alanine transminase, and aspartate transminase). CONCLUSIONS: HCV positive in IBD may induce autoanti-bodies (antinuclear antibodies, antieutrophil cytoplasmic antibody, anti-SSa/SSb) and damage of liver function. In managing IBD patients, physicians should be aware of screening of HCV and prescribe antiviral treatment.
BACKGROUND: Active hemorrhage arising from hepatic injury can be life-threatening and require immediate attention. At present, nonoperative management of abdominal solid organ injuries has become the usual method of care. The purpose of this study was to determine whether hemocoagulase injection alone guided by contrast-enhanced ultrasonography (CEUS) could control active bleeding in rabbit liver. METHODS: The livers of 30 rabbits were punctured with an 18-gauge semiautomatic biopsy needle to create an active bleeding liver model, which was confirmed with CEUS. The animals were randomly divided into two groups: a treatment group (n=15) and a control group (n=15). In the treatment group, hemocoagulase was injected into the bleeding site under CEUS guidance. In the control group, the active bleeding site was treated with normal saline. When these treatment procedures had been performed, lactated Ringer s solution was given to both groups to maintain the mean arterial pressure at 70 mmHg for 1 hour. The intraperitoneal blood loss, hematocrit, mean heart rate, and macroscopic and microscopic examinations were analyzed at the end of the study. RESULTS: CEUS showed hypoechoic and anechoic perfusion defects in active bleeding liver models. Macroscopic and microscopic examinations also supported the results. After the hemocoagulase injection, the former bleeding site appeared on CEUS as an area devoid of contrast. The blood loss was lower in the treatment group than in the control group (38.0±16.6 ml versus 107.9±20.8 ml; t=10.172, P<0.05). The mean hematocrit value and the heart rate were higher in the treatment group than in the control group (hematocrit: 23.9±3.8% versus 18.8±4.1%; t=3.541, P<0.05; heart rate: 250±18 versus 223±15; t=4.551, P<0.01). CONCLUSION: Hemocoagulase injection alone under the guidance of CEUS is a simple and quick method to control blood loss in active liver bleeding.
BACKGROUND: Biliary leak is an uncommon but significant complication following cholecystectomy. Endotherapy is an established method of treatment. However, the optimal intervention is not known. METHOD: Eighty-five patients with postcholecystectomy biliary leaks from July 2000 to March 2009 were retrospectively evaluated. RESULTS: The study population was 20 males and 65 females with a mean age of 42.47 years. Patients presented with abdominal pain (46), jaundice (23), fever (23), abdominal distension (42), or bilious abdominal drain (67). Endoscopic retrograde cholangiopancreatography detected a leak at the cystic duct stump in 45 patients, stricture with middle common bile duct leak in 4, leak from the right hepatic duct in 3, and a ligated common bile duct in 32. Twelve also had bile duct stones. One had a broken T-tube with stones. Endotherapy was possible in 53 patients. Three patients with stones, one with a broken T-tube with stones, and 4 with stricture of the common bile duct with a leak were managed with sphincterotomy and stenting. Eight patients with a cystic duct stump leak with stones were managed with sphincterotomy and stone extraction. Three outpatients and 12 inpatients with a cystic duct stump leak were managed with sphincterotomy and stent and sphincterotomy and nasobiliary drain, respectively. Five patients with a cystic duct stump leak were managed with stenting. Sixteen with coagulopathy were managed with only nasobiliary drain (9) or stent (7). Leak closure was achieved in 100% patients. Four developed mild pancreatitis which improved with conservative treatment. CONCLUSIONS: Endoscopic intervention is a safe and effective method of treatment of postcholecystectomy biliary leaks. However, management should be individualized based on factors such as outpatients or inpatients, presence of stone, stricture, ligature, or coagulopathy.
BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gall-bladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Bax, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61±0.39 vs. 9.78±0.61 cm3, P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08±1.49% vs. 5.49±0.59%, P= 0.0001) along with a decreased percentage of cells in S phase (43.47±2.83% vs. 69.85±1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 and Bax proteins/mRNAs in the NCTD group compared with the control group. CONCLUSION: NCTD inhibits the growth of xenografted tumors of human gallbladder carcinoma in nude mice by inducing apoptosis and blocking the cell cycle in vivo.
BACKGROUND: Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. METHOD: Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. RESULTS: The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. CONCLUSIONS: Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the first choice for diagnostic evaluation of the pancreatic and biliary tree and can be accompanied by a high diagnostic sensitivity and a poor therapeutic outcome. In the current study, we described our experiences in the indications, findings, and technical success of ERCP in a sample of the Iranian population admitted to a referral center in Iran. METHODS: In a retrospective review database-based study, 780 patients (393 males and 387 females; mean age 57.5 years) who had undergone diagnostic and therapeutic ERCP with the primary diagnosis of hepatobiliary disorder between 2006 and 2008 at Taleghani Hospital in Tehran were reviewed. The key data were demographic characteristics, clinical information, laboratory parameters, as well as post-ERCP complications. RESULTS: A history of cholecystectomy was found in about one-third (36.3%) of participants and 80 (10.3%) out of 780 patients had a previous history of biliary stone. A minority (1.4%) of the patients suffered from hepatobiliary carcinomas, and 11 patients had cirrhosis. The most common clinical manifestations in the patients undergoing diagnostic ERCP were icterus (47.3%), weight loss (31.2%), and dark urine (26.9%). Selective biliary cannulation was technically successful in 87.0% of the patients; however, cannulation failed in 13.0%. The most frequent final diagnosis of ERCP was common bile duct stone that was detected in 40.1% of the patients. The ERCP results in 11.0% of the patients were normal. Regarding appropriate treatment, successful stenting was performed in 43 patients (15.2%). Among post-ERCP complications, pancreatitis was the most adverse event with an incidence rate of 3.3%. Other complications including local bleeding, cholangitis and gastrointestinal perforation, rarely occurred. Post-ERCP pancreatitis was reported in 1.8% of men and 3.6% of women (P=0.120). Pancreatitis was more common in women below 70 years than in those who were older than 70 years (3.6% versus 0.5%; OR: 8.216, P=0.015). This might be due to the more functionally active pancreas in younger women than in the older ones. However, other complications were similar in the two age groups. CONCLUSIONS: Based on our experience, ERCP indications, final diagnosis and related complications are comparatively consistent with those reported in other countries. The most common post-ERCP complication is pancreatitis that is more often observed in younger patients.
BACKGROUND: Giant cell tumors are rare and highly malignant tumors of the pancreas. Based on two distinct cell populations, they have been divided into two subtypes corresponding to the osteoclast-like giant cell tumor and the pleomorphic giant cell carcinoma of the pancreas. Distinctive imaging features of the tumors remain uncharacterized. Surgical removal is the only appropriate treatment for them, but responses to chemotherapy or radiotherapy remain undocumented. METHODS: Clinical, radiological, histopathologic, and immunohistochemical features of two cases of giant cell tumor of the pancreas are presented along with a brief review of the literature. RESULTS: En-bloc resection was done successfully in both cases. The patient with an osteoclast-like giant cell tumor remained disease-free with no clinical or radiological evidence of recurrence at 6 months after surgery. However, the patient with the pleomorphic type died 4 months later due to diffuse pulmonary metastasis. CONCLUSIONS: En-bloc surgical resection is the only appropriate treatment for giant cell tumors. The overall prognosis of these tumors is poorer than that of pancreatic ductal adenocarcinoma, especially the pleomorphic type. More studies are required to document the management and outcomes of the tumors.
BACKGROUND: The number of females who undergo liver transplantation is growing and sometimes gynecologic operations are needed to control gynecologic diseases after liver transplantation. METHOD: Total laparoscopic hysterectomy was performed in 2 patients who had undergone liver transplantation, one for adenomyosis and the other for hysteromyoma. RESULTS: It was safe to create a pneumoperitoneum through the umbilical skinfold even though mild adhesion in the pelvic cavity occurred in one patient. The operative times were 95 and 90 minutes, with blood loss of about 100 and 60 ml, respectively. Oral intake, flatus passage, and ambulation recovered within a day, after the operation. No significant changes in liver function were observed except complication of diarrhea caused by Candida albicans in one patient. CONCLUSIONS: The result of the two patients suggest that total laparoscopic hysterectomy is a safe and effective surgical approach for patients who have undergone liver transplantation.
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