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Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been suggested to cause rapid liver hypertrophy among patients having inadequate future liver remnant (FLR). However, ALPPS is still considered as a controversial hepatocellular carcinoma (HCC) treatment, especially for those with cirrhosis. This is ascribed to the high mortality and morbidity. The present study aimed to evaluate the ALPPS safety and feasibility for HCC patients related to hepatitis B virus (HBV). Methods This was a retrospective observational study. Consecutive HCC cases undergoing ALPPS or RH at our hospital between September 2014 and June 2018 were included. The demographic and clinical data of patients were collected, and oncological results of ALPPS patients were compared with those receiving right hepatectomy (RH). Results A total of 14 ALPPS patients and 21 RH patients were consecutively collected between September 2014 and June 2018. All ALPPS patients received stage II operations, with 100% resection of R0. The median growth of FLR between operations was 48% (range, ‒0.06% to 100%) in 17 days (range, 9–30 days). 3 ALPPS patients (21.4%) suffered from severe complications (grade ≥IIIb) according to the Clavien-Dindo grade, including 1 with renal failure, and 2 with the FLR/SLV of

Objective Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. Design 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. Results 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. Conclusions Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

Background To assess resident perspectives on laparoscopic surgery and how it might differ compared to open surgery. Materials and Methods Anonymous surveys were sent to residents who came to hepatic surgery service rotation during Sep 2013 to Aug 2017. Statistical comparisons were conducted using student T-test, comparing mean satisfaction and preferences. Results A total of 80 residents responded to the survey, distributed across the spectrum of training levels. Of the 80 respondents, 9 were in their first year of training, while 18, 41, and 12 were in their second, third, or fourth years of training, respectively. Among them, there were 11 residents were not included in the final analysis. Residents indicated that they preferred open procedures for conferring greater exposure to operating (7.172 ± 1.4646 for open vs 4.414 ± 2.1442 for laparoscopy, p < 0.001). Residents indicated that laparoscopic procedures were preferred in aiding in understanding of the surgical procedure (6.814 ± 1.3323 for open vs 7.407 ± 1.3014 for laparoscopy, p = 0.016). Conclusions These results suggest that residents prefer open procedures for hands-on experience, while laparoscopic procedures confer the advantage of facilitating the learning of a surgical procedure. This provides an opportunity for intervention, as minimally invasive surgeries(MIS) are a major component of modern surgical practice and, therefore, must be an area of strength in the training of surgical residents.

Background and Aim: Immunoglobulin G4-associated cholangitis (IAC) shares many similar symptoms with cholangiocarcinoma (CCA). However, the treatment and the prognosis are substantially different. This study aimed to identify the important markers for the differential diagnosis of these 2 diseases. Methods: Thirty IAC patients and 275 CCA patients were reviewed retrospectively for their clinical symptoms, serological tests, and imaging characteristics. Posttreatment responses were also studied. Results: IgG4 had 100% specificity for IAC at a cutoff of 6 times the upper normal limit. IAC patients had a significantly higher incidence of weight loss (P=0.025) and a higher level of weight loss (P=0.008) than CCA patients. The positive rates of biological markers CA199, CA242, and CEA in CCA and IAC were 81.5% versus 42.9%, 45.5% versus 4.5%, and 29.2% versus 7.1%, respectively. Levels of these tumor markers in CCA were significantly higher than in IAC (P

Background and Aim Inflammatory myofibroblastic tumor of the liver (IMTL) is a very rare benign disease with a good prognosis. The study aims to determine the clinical, radiological, and pathological characteristics of IMTL. The diagnosis and treatment strategies were discussed. Methods A total of 11 patients with pathologically confirmed IMTL receiving treatment over a 15-year period were reviewed retrospectively. The analysis included demographics information and pertinent clinical data. Results obtained from patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC), and metastatic liver cancer (MLC) receiving surgical resection were compared. Results In comparison to HCC, IHCC, and MLC, IMTL has an earlier onset (P

Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. Preoperative UIs are highly correlated with Child score (P

Background To determine more precisely time interval from resection to recurrence of hepatocellular carcinoma (HCC) and to identify the risk factors associated with postoperative recurrence. Methods From January 2004 to December 2007, 178 patients who underwent resection of HCC were followed prospectively for at least 12 months. Recurrence was identified by the digital subtraction angiography (DSA). Demographic, tumor, and disease characteristics were compared between patients with recurrence within 6 months and between 7 and 12 months, and those without recurrence to evaluate for their prognostic significance. Patients with intrahepatic recurrence were treated with trans-arterial chemoembolization (TACE) and re-assessed by CT scans, contrast-enhanced ultrasound, or MRI. Results Recurrence developed in 52 patients between 1 and 6 months, 11 patients between 7 and 12 months, and 115 patients remained disease free for at least 1 year. The recurrence rates of 6 months and 1 year were 29.2% and 35.4%, respectively. No statistically significant difference between was observed. Fourteen (22.2%) patients with recurrence and 11 (9.6%) patients without recurrence had previously presented as multifocal HCC, and the difference is of statistical significance (P = 0.025). The diagnostic accuracy of DSA as validated by other diagnostic methods was 81.8%. Conclusions Recurrences are more likely to develop within the first 6 months after resection for HCC. Multifocal HCC is an important risk factor associated with early recurrence of advanced HCC after hepatectomy. DSA may serve as an important surveillance for early detection of intrahepatic recurrence after surgery. J. Surg. Oncol. 2009;100:488–493. © 2009 Wiley-Liss, Inc.

Background and Objectives Curative hepatic resection (CHR) was a modality that provides possibility of long-term survival for hepatocellular carcinoma (HCC). So far, prognostic factors of male patients with HCC after CHR remain unclear. Purposes of the present study were to identify these factors and to compare them with those for females. Methods Consecutive 151 male and 23 female patients with HCC undergoing CHR were enrolled in this retrospective study. Their prognostic factors were identified by uni- and multi-variate statistical analysis. Results One-, three- and five-year overall and disease-free survival of male patients were 82.4, 51.5, and 43.6%, and 65.8, 33.7, and 21.7%, respectively, with no significant differences compared to females. Univariate analysis showed that tumor size, TNM staging, Edmondson-Steiner grade, serum α-fetoprotein (AFP) level, presence of portal vein tumor thrombosis (PVTT) and satellite nodule were significant for males with HCC, but only Edmondson-Steiner grade, presence of PVTT and satellite nodule were independent. For females, Edmondson-Steiner grade was the single potential indicator for survival. Conclusions Malignant degree and invasive phenotypes were main factors that independently influenced survival of male patients with HCC after CHR. Among them, histological grade, which was also potentially significant for females, was the most powerful survival predictor. J. Surg. Oncol. 2007;95:298–303. © 2007 Wiley-Liss, Inc.

A 75-year-old man presented with a liver mass detected by abdominal ultrasonography for health check-up.

To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools.Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network.In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α.EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

Inflammatory myofibroblastic tumor of the liver (IMTL) is a very rare benign disease with a good prognosis. The study aims to determine the clinical, radiological, and pathological characteristics of IMTL. The diagnosis and treatment strategies were discussed.A total of 11 patients with pathologically confirmed IMTL receiving treatment over a 15-year period were reviewed retrospectively. The analysis included demographics information and pertinent clinical data. Results obtained from patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC), and metastatic liver cancer (MLC) receiving surgical resection were compared.In comparison to HCC, IHCC, and MLC, IMTL has an earlier onset (P 0.001). IMTL patients had significantly lower aspartate aminotransferase (P = 0.003) and higher alkaline phosphatase (P = 0.034) than HCC patients, and higher gamma-glutamyl transpeptidase (P = 0.010) than MLC patients. Increased serum α-fetoprotein level was detected in only one patient. Serum α-fetoprotein was significantly lower in patients with IMTL (P = 0.000) than in those with HCC but not IHCC (P = 0.558) or MLC (P = 0.514). In contrast to elevated serum CA19-9 in patients with HCC/IHCC/MLC, the serum CA19-9 in IMTL cases was generally normal (vs HCC P = 0.008; vs IHCC P = 0.000; vs MLC P = 0.022). In nine IMTL patients, the tumor appeared as a hypoechogenic solid mass on the ultrasonography. In contrast, most patients with HCC, IHCC, or MLC showed hybrid echo. In contrast computed tomography and magnetic resonance imaging, the lesion of IMTL and MLC appeared as peripheral enhancement.Lab tests, imaging features, and patient history are helpful in the differential diagnosis of IMTL from HCC/IHCC/MLC. Surgical resection is curative for IMTL.

We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha-fetoprotein (AFP)-negative small hepatic lesions.Small hepatic lesions (less than 2 cm in diameter) usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result.A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography (DSA), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced ultrasound (CEUS), or positron emission tomography-computed tomography (PET-CT) based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires.Hepatocellular carcinoma (HCC) diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively.DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

The rising of individualized therapy requires nutritional risk screening has become a major topic for each particular disease, yet most of the screenings were for malignancies, less for benign diseases. There is no report on the screening of patients with benign liver tumors postoperatively. We aim to evaluate the nutritional support strategies post operation for benign liver tumors through nutritional risk screening.In this prospective, randomized, controlled study, 95 patients who underwent hepatectomy for benign tumors were divided into two groups. Fifty patients in the control group were given routine permissive underfeeding nutritional supply (75 kJ/kg/d), and 45 patients in the experimental group were given lower energy (42 kJ/kg/d) in accordance of their surgical trauma. Routine blood tests, liver/kidney function were monitored before surgery and at the day 1, 3, 5, 9 after surgery, patients were observed for the time of flatus, complications, length of hospitalization (LOH), nutrition-related costs, and other clinical parameters. This completed study is registered with Clinicaltrials.gov, number NCT01292330.The nutrition-related expenses (494.0±181.0 vs. 1,514.4±348.4 RMB, P0.05) and the total hospital costs (18,495.2±4735.0 vs. 21,432.7±8,291.2 RMB, P0.05) for patients in the experimental group were significantly lower than those in the control group. Meanwhile, the lowered energy supply after the surgeries did not have adverse effects on clinical parameters, complications, and LOH.Patient with benign liver tumors can adopt an even lower postoperative nutritional supply that close to that for mild non-surgical conditions, and lower than the postoperative permissive underfeeding standard.

Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC.Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC.Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC.GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.

Background The inhibition of inflammation exerts benefits following massive hepatectomy in animals but not in the clinic. The aim of this study was to investigate the effectiveness and mechanism of ulinastatin on liver function and outcomes following hepatectomy. Methods One hundred seventy-six patients undergoing hepatectomy were randomized into the treatment group (n = 86) and the control group (n = 90), receiving ulinastatin 150,000 U twice daily for 3 days and saline vehicle, respectively. Liver function, coagulation, thrombokinase, lymphocyte subsets CD4 and CD8, C-reactive protein, inducible nitric oxide synthase, and cytokines were measured. Clinical outcomes were also evaluated. Results Serum alanine transaminase, aspartate transferase, inducible nitric oxide synthase, and tumor necrosis factor–α levels were significantly lower after ulinastatin treatment, and the response of bilirubin was delayed. The benefits of ulinastatin were shown mainly in major hepatectomy earlier after surgery. The treatment significantly reduced hospital length of stay and recovery-related cost. Conclusions Ulinastatin protects liver function and improves clinical outcomes, possibly via the inhibition of inflammation and oxidation at an earlier stage following major hepatectomy.

To determine more precisely time interval from resection to recurrence of hepatocellular carcinoma (HCC) and to identify the risk factors associated with postoperative recurrence.From January 2004 to December 2007, 178 patients who underwent resection of HCC were followed prospectively for at least 12 months. Recurrence was identified by the digital subtraction angiography (DSA). Demographic, tumor, and disease characteristics were compared between patients with recurrence within 6 months and between 7 and 12 months, and those without recurrence to evaluate for their prognostic significance. Patients with intrahepatic recurrence were treated with trans-arterial chemoembolization (TACE) and re-assessed by CT scans, contrast-enhanced ultrasound, or MRI.Recurrence developed in 52 patients between 1 and 6 months, 11 patients between 7 and 12 months, and 115 patients remained disease free for at least 1 year. The recurrence rates of 6 months and 1 year were 29.2% and 35.4%, respectively. No statistically significant difference between was observed. Fourteen (22.2%) patients with recurrence and 11 (9.6%) patients without recurrence had previously presented as multifocal HCC, and the difference is of statistical significance (P = 0.025). The diagnostic accuracy of DSA as validated by other diagnostic methods was 81.8%.Recurrences are more likely to develop within the first 6 months after resection for HCC. Multifocal HCC is an important risk factor associated with early recurrence of advanced HCC after hepatectomy. DSA may serve as an important surveillance for early detection of intrahepatic recurrence after surgery.

Aim Comprehensive data regarding elderly patients with hepatocellular carcinoma (HCC) were limited. The present study aims to widen the knowledge based on patients in China. Methods Fifty-four elderly (≥65 years) and 125 non-elderly HCC patients undergoing hepatectomy were enrolled in this retrospective study. Clinicopathological features and post-surgical survival were compared between two groups. Prognostic indicators of elderly patients were defined by uni- and multivariate analyses. Results Contrast to non-elderly patients, the elderly presented significantly lower rates of HBsAg positivity, Child–Pugh grade A, α-fetoprotein (AFP) marked elevation, portal vein tumour thrombosis (PVTT), satellite nodule, and intrahepatic recurrence, smaller tumour sizes, earlier TNM staging and better histological differentiation. No significant differences were found in perioperative mortality rate and post-surgical survival between two groups. PVTT and Edmondson-Steiner grading were identified as independent prognostic indicators of both overall and disease-free survival by multivariate analysis, whereas Child–Pugh grading independently affected the overall survival. Conclusions HCC in the elderly seemed to be less HBV-associated, less progressive and less aggressive than that in the non-elderly. Hepatectomy for the elderly could make a satisfactory prognosis and be well tolerated. Some tumour-related factors independently predict the prognosis of elderly HCC patients, and their liver function status should be further valued.

How to properly manage neuroendocrine liver metastasis (NELM) remains debatable, and only limited clinical data have been published from Asian population. The objective of this study is to identify possible prognostic factors affecting overall survival time and to provide a guideline for future clinical practice. A retrospective study was performed on 1286 patients who had neuroendocrine tumors in our specialized center, and data from 130 patients who had NELM were summarized. Demographic and clinicopathologic data, tumor grade, treatment method, and prognosis were statistically analyzed. Most of the NELMs originated from pancreas (65.4%). Important prognostic factors that included tumor location and size were identified with multivariate analysis. Patients with either primary tumor resection or liver metastasis resection showed a 5-year survival of 35.7% or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year survival. More importantly, resection was performed on 7 patients with grade 3 (G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%, and 28.6%, respectively, whereas the other 9 G3 patients without resection died within 3 years. P = 0.49 comparing the resected group with nonresected group in G3 patients. Besides, the overall 5-year survival rates for resected and nonresected patients were 40.5% and 5.4%, respectively. Multiple prognostic factors influenced the overall outcome of NELM including patient age, tumor location, and size, etc. Aggressive surgical approaches could be considered for maximum survival time disregarding the pathological grade of the tumor. Study with larger sample size should be considered to reevaluate the recommendation of the WHO guidelines for G3 neuroendocrine tumors.