BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition.
DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD.
RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors, such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia-reperfusion injury is considered the direct cause. Potential managements which are helpful to improve graft function were investigated. Some of them are promising.
CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1) bilirubin ≥10 mg/dL on postoperative day 7; (2) international normalized ratio ≥1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase >2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses into primary non-function, the patients need to be treated with re-transplantation.

BACKGROUND: Macrophages are widely-distributed innate immune cells playing diverse roles in various physiological and pathological processes. The primary function of macrophages is to phagocytize and clear invading pathogens.
DATA SOURCES: A systematic search of PubMed was performed to identify relevant studies in English language literature using the key words such as macrophage and inflammation. A total of 122 articles related to inflammatory response of macrophages in infection were systematically reviewed.
RESULTS: The inflammatory responses of macrophages triggered by infection comprise four interrelated phases: recognition of pathogen-associated molecular patterns by pattern-recognition receptors expressed on/in macrophages; enrichment of quantity of macrophages in local infected tissue by recruitment of circulating monocytes and/or in situ proliferation; macrophage-mediation of microbicidal activity and conversion to anti-inflammatory phenotype to terminate anti-infectious response and to promote tissue repair. Complicated regulation of macrophage activation at molecular level recognized in the past decade is also reviewed, including intracellular multiple signaling molecules, membrane molecules, microRNAs and even epigenetic-associated molecules.
CONCLUSION: The inflammatory response of macrophages in infection is an orderly and complicated process under elaborate regulation at molecular level.

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.
METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence, and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed.
RESULTS: The cumulative recurrence-free survival rates at 1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase (before 2 years; n=164) and late phase (after 2 years; n=83). Cox's multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status (P=0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1 of the 2 early recurrence risk factors (multiplicity of tumors ≥2 and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6, respectively).
CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

BACKGROUND: The global risk of hepatocellular carcinoma (HCC) is largely due to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years, however, an increased prevalence of non-viral HCC has been noted. The clinical impact of the presence/absence of viral infections in HCC remains controversial. The present study aimed to assess the effect of hepatitis viruses on demographics, clinical and pathological features and long-term outcome in a large cohort of Romanian patients who underwent surgery for HCC.
METHODS: The study included 404 patients with HCC who had undergone resection, transplantation or radiofrequency ablation at a single institution between 2001 and 2010. The patients were divided into four groups: 85 patients with hepatitis B virus infection (HBV group), 164 patients with hepatitis C virus infection (HCV group), 39 patients with hepatitis B and C virus co-infection (HBCV group), and 116 patients without viral infection (non-BC group).
RESULTS: The patients of both HBV (56.0±11.3 years) and HBCV groups (56.0±9.9 years) were significantly younger than those of the HCV (61.0±8.5 years, P=0.001) and non-BC groups (61.0±13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis was significantly lower in the non-BC group (47%) than in any other subsets (72%-90%, P<0.002). Furthermore, the non-BC patients were more advanced according to the Barcelona Clinic Liver Cancer stages than the patients of the HCV or HBCV groups (P<0.020); accordingly, they were more frequently assessed beyond the Milan criteria than any other groups (P=0.001). No significant differences in the disease-free or overall survival rates were observed among these groups.
CONCLUSIONS: Patients with non-viral HCC are diagnosed at advanced ages and stages, a situation plausibly due to the poor effectiveness of cancer surveillance in community practice. The presence of viral infections does not appear to impair the long-term prognosis after surgical treatment in patients with HCC; however, there is a trend for worse disease-free survival rates in HBCV patients, though statistical significance was not reached.

BACKGROUND: Angiographic embolization (AE) as an adjunct non-operative treatment of intrahepatic arterial bleeding has been widely used. The present study aimed to evaluate the efficacy of selective AE in patients with hepatic trauma.
METHODS: Seventy patients with intrahepatic arterial bleeding after blunt abdominal trauma who had undergone selective AE in 10 years at this institution were retrospectively reviewed. The criteria for selective AE included active extravasation on contrast-enhanced CT, an episode of hypotension or a decrease in hemoglobin level during the non-operative treatment. The data of the patients included demographics, grade of liver injuries, mechanism of blunt abdominal trauma, associated intra-abdominal injuries, indications for AE, angiographic findings, type of AE, and AE-related hepatobiliary complications.
RESULTS: In the 70 patients, 32 (45.71%) had high-grade liver injuries. Extravazation during the early arterial phase mainly involved the right hepatic segments. Thirteen (18.57%) patients underwent embolization of intrahepatic branches and the extrahepatic trunk and these patients all developed AE-related hepatobiliary complications. In 19 patients with AE-related complications, 14 received minimally invasive treatment and recovered without severe sequelae.
CONCLUSIONS: AE is an adjunct treatment for liver injuries. Selective and/or super-selective AE should be advocated to decrease the incidence and severity of AE-related hepatobiliary complications.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE) in combination with continuous renal replacement therapy (CRRT) (PE+CRRT) for AFLP still needs evaluation.
METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT.
RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results, and they were cured and discharged home after the treatment. One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after 2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively.
CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

BACKGROUND: FBW7 is a tumor suppressor which regulates a network of proteins with central roles in cell division, cell growth and differentiation. This study aimed to evaluate the role of FBW7 in chemosensitivity and epithelial-mesenchymal transition (EMT) in different hepatocellular carcinoma (HCC) cell lines and to investigate the relevant underlying mechanisms.
METHODS: Different human HCC cell lines (Hep3B, Huh-7, and SNU-449) were cultured. The cell viability was evaluated by cell counting kit-8, and FBW7 mRNA transcription and protein expression were quantitated by real-time PCR and Western blotting. Expressions of vimentin (mesenchymal biomarker) and E-cadherin (epithelial biomarker) were evaluated by Western blotting and immunocytochemistry. Cell invasion was assayed by Transwell migration, and FBW7 plasmid or siRNA was used to evaluate the effect of FBW7 overexpression or silencing on cell chemosensitivity.
RESULTS: FBW7 expression affected tumor cell chemosensitivity to doxorubicin and tumor cell invasive capacity in different HCC cell lines. FBW7hi (high FBW7 expression) Hep3B and FBW7mi (median FBW7 expression) Huh-7 cells were more sensitive to doxorubicin and lower in invasive capacity than FBW7lo (low FBW7 expression) SNU-449 cells. Silencing of FBW7 in Huh-7 and Hep3B cells induced the resistance to doxorubicin and enhanced cell invasion, whereas overexpression of FBW7 in SNU-449 cells restored the sensitivity to doxorubicin and significantly reduced invasive capacity. Furthermore, doxorubicin induced EMT toward mesenchyme in HCC cells. Downregulation of FBW7 in Huh-7 and Hep3B cells or upregulation of FBW7 in SNU-449 cells altered the direction of EMT.
CONCLUSIONS: The level of FBW7 expression impacted the tumor resistance to doxorubicin and the invasion capability of HCC cells. FBW7 therefore may be a potential target for the chemotherapy of HCC through the regulation of EMT.

BACKGROUND: Chronic pancreatitis (CP) is a risk factor of pancreatic adenocarcinoma (PA). The discovery of a pancreatic head lesion in CP frequently leads to a pancreaticoduodenectomy (PD) which preceded by a multidisciplinary meeting (MM). The aim of this study was to evaluate the relevance between this indication of PD and the definitive pathological results.
METHODS: Between 2000 and 2010, all patients with CP who underwent PD for suspicion of PA without any histological proof were retrospectively analyzed. The operative decision has always been made at an MM. The definitive pathological finding was retrospectively confronted with the decision made at an MM, and patients were classified in two groups according to this concordance (group 1) or not (group 2). Clinical and biological parameters were analyzed, preoperative imaging were reread, and confronted to pathological findings in order to identify predictive factors of malignant degeneration.
RESULTS: During the study period, five of 18 (group 1) patients with CP had PD were histologically confirmed to have PA, and the other 13 (group 2) did not have PA. The median age was 52.5±8.2 years (gender ratio 3.5). The main symptoms were pain (94.4%) and weight loss (72.2%). There was no patient's death. Six (33.3%) patients had a major complication (Clavien-Dindo classification ≥3). There was no statistical difference in clinical and biological parameters between the two groups. The rereading of imaging data could not detect efficiently all patients with PA.
CONCLUSIONS: Our results confirmed the difficulty in detecting malignant transformation in patients with CP before surgery and therefore an elevated rate of unnecessary PD was found. A uniform imaging protocol is necessary to avoid PD as a less invasive treatment could be proposed.

BACKGROUND: Multi-visceral resection for extra-pancreatic carcinoma is an uncommon procedure that may offer palliation and potential cure but must be balanced against the risk for morbidity and mortality.
METHODS: A retrospective analysis was made of patients who had undergone multi-visceral resection of non-pancreatic carcinoma. Factors influencing this procedure included histology, pathologic confirmation of pancreaticoduodenal invasion, tumor clearance, peri-operative morbidity and outcome.
RESULTS: Sixteen patients had en bloc resection including a Whipple procedure (6 patients) and a distal resection (10). Primary pathology mostly originated from the stomach and adenocarcinoma was predominately histological. An R0 resection was made in 13 patients, and actual cancer invasion or abutment into the pancreas or duodenum was confirmed pathologically in 11 patients. Twelve patients suffered from at least one complication. Ten patients required therapeutic intervention for complications. There were 2 in-hospital deaths. The median survival of deceased patients was 7.5 months. Six patients are alive at a median of 21 months, and 4 patients have no evidence of disease to the present.
CONCLUSIONS: Multi-visceral resections for extra-pancreatic carcinoma are associated with substantial morbidity that requires therapeutic intervention. Clinical determination of pancreaticoduodenal abutment and achievement of tumor clearance is excellent. Survival with and without recurrent disease is often limited, supporting that it is necessary to cautiously perform the aggressive procedures in consideration of neoadjuvant therapy.

BACKGROUND: Postoperative pancreatic fistula is one of the most common complications after pancreatectomy. This study aimed to assess the occurrence and severity of pancreatic fistula after central pancreatectomy.
METHODS: The medical records of 13 patients who had undergone central pancreatectomy were retrospectively studied, together with a literature review of studies including at least five cases of central pancreatectomy. Pancreatic fistula was defined and graded according to the recommendations of the International Study Group on Pancreatic Fistula (ISGPF).
RESULTS: No death was observed in the 13 patients. Pancreatic fistula developed in 7 patients and was successfully treated non-operatively. None of these patients required re-operation. A total of 40 studies involving 867 patients who underwent central pancreatectomy were reviewed. The overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of 279 patients, 250 (89.6%) had grade A or B fistulae of ISGPF and were treated non-operatively, and the remaining 29 (10.4%) had grade C fistulae of ISGPF. In 194 patients, 15 (7.7%) were re-operated upon. Only one patient with grade C fistula of ISGPF died from multiple organ failure after re-operation.
CONCLUSION: Despite the relatively high occurrence, most pancreatic fistulae after central pancreatectomy are recognized a grade A or B fistula of ISGPF, which can be treated conservatively or by mini-invasive approaches.

BACKGROUND: Hypertriglyceridemia induces acute recurrent pancreatitis, but its role in the etiology of chronic pancreatitis (CP) is controversial. This study aimed to evaluate the clinical, laboratory and radiological findings of 7 patients with CP due to type 1 hyperlipidemia compared to CP patients with other or undefined etiological factors.
METHODS: We retrospectively analyzed the clinical, laboratory and radiological findings of 7 CP patients with type 1 hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7 patients had multiple episodes of acute pancreatitis and had features of CP on abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasonography.
RESULTS: All CP patients were classified into two groups: a group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58). The mean triglyceride level was 2323±894 mg/dL in the first group. Age at the diagnosis of CP in the first group was significantly younger than that in the second group (16.5±5.9 vs 48.3±13.5, P<0.001). The number of episodes of acute pancreatitis in the first group was significantly higher than that in the second group (15.0±6.8 vs 4.0±4.6, P=0.011). The number of splenic vein thrombosis in the first group was significantly higher than that in the second group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age was an independent predictor of CP due to hypertriglyceridemia (r=0.418, P=0.000).
CONCLUSIONS: Type 1 hyperlipidemia appears to be an etiological factor even for a minority of patients with CP. It manifests at a younger age, and the course of the disease might be severe.

Residual cystic duct stones (CDSs) after cholecystectomy have been recognized as a cause of post-cholecystectomy pain. This study was undertaken to determine the incidence of CDSs during laparoscopic cholecystectomy (LC). A cohort of 330 consecutive patients (80 males and 250 females) undergoing LC between November 2006 and May 2010 was studied. Their age ranged between 16 and 88 years (median 50, IQR: 36.62). The data were prospectively collected of preoperative liver function tests, imaging, the presence of intraoperative CDSs, and common bile duct stones at on-table cholangiogram. CDSs were detected intraoperatively in 64 of the 330 patients (19%). Ultrasound failed to detect CDSs in any of these cases. Deranged liver function tests were noted in 73% of the patients with CDSs and in 57% without CDSs. Common bile duct stones were detected in 9% (29) of the 330 patients. CDSs occur commonly at routine cholecystectomy, and preoperative investigations are not helpful in their diagnosis. As CDSs may lead to postoperative morbidity, they should be actively sought out during surgery if present.

BACKGROUND: One of the best treatments for isolated hepatocellular carcinoma in the caudate lobe is major hepatectomy with caudate lobectomy, but it is not suitable for patients with poor liver function reserve. Isolated caudate lobectomy, which is a very difficult operation, is thus an alternative option.
METHODS: Here we report an isolated caudate lobectomy with an anterior approach in the treatment of a large hepatocellular carcinoma with underlying cirrhosis, with focus on the technical aspects.
RESULTS: In the operation, both the left and right lobes of the liver were mobilized. Hepatotomy was done along the round ligament where parenchymal transection was minimal. After exposure of the left and middle hepatic veins and the hilar plate, the caudate lobe and the tumor were resected en bloc with a 5-mm margin.
CONCLUSION: Isolated caudate lobectomy can be performed safely with this anterior approach on patients with poor liver function reserve.