Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

Innate-like bystander-activated CD38+ HLA-DR+ CD8+ T cells play a pathogenic role in patients with chronic hepatitis C.

BACKGROUND AND AIMS: HCV-specific T cells are few and exhausted in patients with chronic hepatitis C (CHC). Whether these T cells are responsible for the liver damage and fibrosis is still debated. However, cluster of differentiation 38-positive (CD38+ ) human leukocyte antigen DR-positive (HLA-DR+ ) CD8+ T cells are regarded as bystander CD8+ T cells that cause liver injury in acute hepatitis. We propose that these innate CD8+ T cells play a pathogenic role in CHC. METHODS: Lymphocytes from peripheral blood were obtained from 108 patients with CHC and 43 healthy subjects. Immunophenotyping, functional assays, T-cell receptor (TCR) repertoire, and cytotoxic assay of CD38+ HLA-DR+ CD8+ T cells were studied. RESULTS: The percentage of CD38+ HLA-DR+ CD8+ T cells increased significantly in patients with CHC. These cells expressed higher levels of effector memory and proinflammatory chemokine molecules and showed higher interferon-γ production than CD38- HLA-DR- CD8 T cells. They were largely composed of non-HCV-specific CD8+ T cells as assessed by HLA-A2-restricted pentamers and next-generation sequencing analysis of the TCR repertoire. In addition, these CD38+ HLA-DR+ CD8+ T cells had strong cytotoxicity, which could be inhibited by anti-DNAX accessory molecule 1, anti-NKG2 family member D, and anti-natural killer NKp30 antibodies. Lastly, the percentage of CD38+ HLA-DR+ CD8+ T cells was significantly associated with liver injury and fibrosis and decreased significantly along with serum alanine aminotransferase normalization after successful direct-acting antiviral treatment. CONCLUSIONS: The TCR-independent, cytokine-responsive bystander CD38+ HLA-DR+ CD8+ T cells are strongly cytotoxic and play a pathogenic role in patients with CHC.

Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.

Fish Oil, Se Yeast, and Micronutrient-Enriched Nutrition as Adjuvant Treatment during Target Therapy in a Murine Model of Lung Cancer.

Despite the effectiveness of primary treatment modalities for cancer, the side effects of treatments, medication resistance, and the deterioration of cachexia after disease progression lead to poor prognosis. A supportive treatment modality to overcome these limitations would be considered a major breakthrough. Here, we used two different target drugs to demonstrate whether a nutraceutical formula (fish oil, Se yeast, and micronutrient-enriched nutrition; NuF) can interfere with cancer cachexia and improve drug efficacy. After Lewis lung cancer (LLC) tumor injection, the C57BL/6 mice were orally administered targeted therapy drugs Iressa and Sutent alone or combined with NuF for 27 days. Sutent administration effectively inhibited tumor size but increased the number of lung metastases in the long term. Sutent combined with NuF had no significant difference in tumor weight and metastasis compare with Sutent alone. However, NuF slightly attenuated metastases number in lung may via mesenchymal marker N-cadherin suppression. NuF otherwise increased epithelial-like marker E-cadherin expression and induce NO-mediated intrinsic apoptotic pathway in tumor cells, thereby strengthening the ability of the targeted therapy drug Iressa for inhibiting tumor progression. Our results demonstrate that NuF can promote the anticancer effect of lung cancer to targeted therapy, especially in Iressa, by inhibiting HIF-1α and epithelial-mesenchymal transition (EMT) and inducing the apoptosis of lung cancer cells. Furthermore, NuF attenuates cancer-related cachectic symptoms by inhibiting systemic oxidative stress.

Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment.

BACKGROUND: The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. MATERIALS AND METHODS: A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. RESULTS: Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. CONCLUSION: The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.

Models to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND AND OBJECTIVES: Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS: Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS: Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001). CONCLUSION: Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection.

Low-dose anti-hepatitis B immunoglobulin regimen as prophylaxis for hepatitis B recurrence after liver transplantation.

BACKGROUND: Combination of anti-hepatitis B immunoglobulin (HBIg) and antiviral nucleotide/nucleoside is the most common regimen for prophylaxis against hepatitis B virus (HBV) recurrence. However, what the optimal regimen is for HBIg administration remains subject to debate. METHODS: Two hundred and thirty-two HBV patients who had liver transplantation were included in this study. According to the decline rate of HBIg, the patients were divided into quick (group Q, n = 95) and slow decline groups (group S, n = 137). Quick HBIg decline was defined as anti-HBs titer <200 IU/mL at postoperative month (POM) 1, when 24 000 IU of HBIg was given perioperatively. HBV recurrence was defined as reappearance of hepatitis B surface antigen (HBsAg). RESULTS: After a mean (range) follow-up of 42.2 (24.1-76.8) months, the HBV recurrence rate was 12.1% for all 232 patients. The median (interquartile) HBIg titer was 96.2 (41.0-158.0) IU in group Q patients, compared to 418.0 (298.8-692.8) IU in group S patients at POM 1 (P < .001). For the patients in group Q, 18 patients (18.9%) had HBV recurrence; this was higher than the 10 (7.3%) patients in group S (P = .013). Multivariate analysis showed that quick HBIg decline and hepatocellular carcinoma recurrence were the risk factors for HBV recurrence. CONCLUSION: Perioperative low-dose HBIg and antiviral nucleotide/nucleoside can effectively prevent HBV recurrence in patients with slow HBIg decline. For patients with quick HBIg decline, the idealized HBIg and antiviral agent regimen should be adjusted to establish an effective regimen as prophylaxis against HBV recurrence.

PlantTalk: A Smartphone-Based Intelligent Hydroponic Plant Box.

This paper proposes an IoT-based intelligent hydroponic plant factory solution called PlantTalk. The novelty of our approach is that the PlantTalk intelligence can be built through an arbitrary smartphone. We show that PlantTalk can flexibly configure the connections of various plant sensors and actuators through a smartphone. One can also conveniently write Python programs for plant-care intelligence through the smart phone. The developed plant-care intelligence includes automatic LED lighting, water spray, water pump and so on. As an example, we show that the PlantTalk intelligence effectively lowers the CO2 concentration, and the reduction speed is 53% faster than a traditional plant system. PlantTalk has been extended for a plant factory called AgriTalk.

Stapleless laparoscopic left lateral sectionectomy for hepatocellular carcinoma: reappraisal of the Louisville statement by a young liver surgeon.

BACKGROUND: Laparoscopic liver resection has been regarded as the standard treatment for liver tumors located at the left lateral liver sector. However, few studies have reported the results of laparoscopic left lateral sectionectomy (LLS) for HCC, not to mention the feasibility of this emerging technique for the less experienced liver surgeons. The current study would reappraise the Louisville statement by examining the outcome of LLS performed by a young liver surgeon. METHODS: We retrospectively reviewed two separate groups of patients who underwent open or laparoscopic left lateral sectionectomies at Chung Gung Memorial Hospital, Linkou. All laparoscopic hepatectomies were performed by the index young surgeon following a stepwise stapleless LLS. The surgical results and oncological outcomes of laparoscopic vs. open hepatectomies (LH and OH, respectively) with the surgical indication of HCC at left lateral liver sector were further compared and analyzed. RESULTS: 18 of 29 patients in the laparoscopic group and 75 patients in the conventional open group had primary HCC. The demographic data was essentially the same for the two groups. Statistical analysis revealed that the LH group had smaller tumor size, higher blood transfusion requirement, longer duration of inflow control and parenchymal transection, and longer operation time. However, no significant difference was observed in terms of complication rate, mortality rate, and hospital stay between the two groups. After adjusting for tumor size, LH and OH showed no statistical difference in the amount of blood transfusion, operation time and patient survival. CONCLUSIONS: This study demonstrated that stapleless LLS is a safe and feasible procedure for less experienced liver surgeons to resect HCC located at the left lateral liver sector. This stepwise stapleless LSS can not only achieve surgical results comparable to OH but also can provide a platform for liver surgeons to apply laparoscopic technique before conducting more complicated liver resections.

Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy.

BACKGROUND: Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved. METHODS: A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed. RESULTS: Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07-2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99-1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors. CONCLUSION: The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.

Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer.

Activating mutation of epidermal growth factor receptor (EGFR) is correlated with malignant lung tumor. In our study, we demonstrated that recombinant LZ-8 (rLZ-8), a medicinal mushroom Ganoderma lucidum protein, induced cell cycle arrest and apoptosis by downregulating the expression of wild-type and mutated EGFR and inhibiting EGFR downstream effectors, AKT and ERK1/2 in lung cancer cells. We showed that rLZ-8 effectively inhibited lung cancer progression and suppressed EGFR expression of lung tumor lesions in mouse model. Functional studies revealed that rLZ-8 reduced the amount of EGFR in cell membranes by altering EGFR localization to enhance the EGF-induced degradation of EGFR. Mechanistically, we demonstrated that rLZ-8 bound to EGFR to induce EGFR autophosphorylation at tyrosine1045 and trigger ubiquitination by inducing the formation of EGFR/Cbl complexes, resulting in the degradation of EGFR; however, Cbl-shRNA abolished rLZ-8-induced EGFR degradation. We provide the first evidence showing that rLZ-8 inhibits growth and induces apoptosis of lung cancer cells by promoting EGFR degradation. The current findings therefore suggest a novel anti-cancer function of rLZ-8 that targeting EGFR overexpression or mutation as well as EGFR-dependent processes in cancer cells.

Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis.

BACKGROUND: Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear. METHODS: Surgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry. RESULTS: Clinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5-47) vs. 53 (ranged 33-85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine-homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis. CONCLUSION: Metabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid-base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.

Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.

BACKGROUND: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. METHODS: All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis. RESULTS: Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage. CONCLUSION: Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.

Microscope-assisted hepatic artery reconstruction in adult living donor liver transplantation-A review of 325 consecutive cases in a single center.

BACKGROUND: Despite the technical and medical improvements in the recent years, hepatic artery thrombosis (HAT) remains a devastating complication after living donor liver transplantation (LDLT). We described our surgical techniques and monitoring protocols for hepatic artery reconstruction. We reported one of the lowest incidence rates of HAT in the literature. METHODS: Between 2008 and 2015, a total of 325 LDLTs performed at our institute were retrospectively analyzed. Under microscope assistance, all hepatic artery anastomosis were performed in a risk-free and back-wall first manner. We collected donors' and recipients' demographics, operative procedures, and outcome. RESULTS: A total of 325 adult LDLTs were enrolled in the study. Of these, 297(91.4%) were right liver graft. The mean diameter of the hepatic arteries of the graft was 1.9 ± 0.3 mm. A single HA anastomosis was performed in 310 patients (95.4%). The 1-, 3-, and 5-year overall patient survival rates were 84.8%, 76.8%, and 75.2%, respectively. Only one (0.3%) episode of HAT was encountered in our series. The patient was treated successfully with nonsurgical management. CONCLUSION: Our study showed that the occurrence of HAT is avoidable. Identifying risk factors associated with HAT, meticulous surgical techniques, and careful routine flow monitoring are mandatory to avoid disastrous complications.

Prognostic impact and risk factors of low body mass index in patients undergoing liver transplantation.

We aimed to investigate the effect of body mass index (BMI) on the overall survival rates and to identify the risk factors associated with adverse outcomes. A total of 381 adult-to-adult living donor liver transplantations performed were retrospectively analyzed. These patients were classified according to the BMI categories established by the World Health Organization: The underweight group (BMI<18.5 kg/m2 ) and the non-underweight group (BMI≥18.5 kg/m2 ). The underweight group had significantly worse outcomes, compared with that of the non-underweight group (5-year overall survival: 45.6% vs 74.6%, P<.001). Underweight patients with CD4/CD8 ratio <1.4 had a significant worse prognosis, compared with those with CD4/CD8 ratio ≥1.4. (The 1-, 3-, and 5-year overall patient survival rates in both groups were 71.0% vs 20%, 58.9% vs 0%, and 53.6% vs 0%, respectively, P=.002.) In the multivariate analysis, only CD4/CD8 ratio <1.4 was an independent poor prognostic factor (hazard ratio=7.063, 95% confidence interval=1.329-37.547, P=.022). CONCLUSIONS: Pre-operative CD4/CD8 ratio <1.4 is an independent poor prognostic indicator for underweight patients undergoing liver transplantation. Early intervention in replenishing the nutrient deficit and cautious use of immunosuppressive regimens are essential to prepare this high-risk population for a more successful liver transplantation.

Colorectal cancer cell-derived interleukin-6 enhances the phagocytic capacity and migration of THP-1 cells.

Macrophages perform a versatile range of functions in response to environmental stimuli. In the present study, we evaluated whether interleukin-6 (IL-6), a cytokine released from colorectal cancer (CRC) cells and associated with CRC pathogenesis and metastasis, modulates the phagocytic capacity and migratory ability of macrophages, using a monocyte-macrophage THP-1 cell model and human peripheral monocytes. We found that CRC cells enhanced the phagocytic capacity and migration of THP-1 cells and human peripheral monocytes. CRC cell culture supernatants and recombinant IL-6 neutralized with anti-IL-6 and anti-gp130 antibodies considerably decreased IL-6-mediated phagocytosis by and migration of THP-1 cells and human peripheral monocytes, via the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Our data suggest that CRC cells secreting IL-6 via STAT3 phosphorylation can enhance the phagocytic capacity and migration of macrophages in the tumor microenvironment.

Impact of spontaneous tumor rupture on prognosis of patients with T4 hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Compare the outcomes of three groups of patients with T4 hepatocellular carcinoma (HCC): tumor rupture with shock (RS group), tumor rupture without shock (R group), and no tumor rupture (NR group). MATERIALS AND METHODS: We retrospectively reviewed 221 patients with T4 HCC from 2010 to 2012. The clinical background and prognosis were analyzed. RESULTS: Overall in-hospital mortality rate was 18.1%; overall median survival time was 4 months. The NR group were more likely to have multiple and infiltrative tumors (P < 0.001). Relative to the NR group, the R + RS group had better survival rates at 6 months (49.2% vs. 32.2%), 1 year (35.3% vs. 21.0%), 3 years (22.5% vs. 11.0%), and 5 years (17.7% vs. 5.5%) (P = 0.010). Patients in the RS group had a higher in-hospital mortality rate, but significantly better long-term survival than the NR and R group (P < 0.001). Multivariate analysis indicated that Child-Pugh class B or C, presence of portal venous thrombosis, and absence of shock were significantly associated with poor survival. CONCLUSION: Patients with tumor rupture and shock had worse in-hospital survival. However, patients without decompensated liver cirrhosis and portal venous thrombosis, and eligible for curative treatment had favorable long-term outcome. J. Surg. Oncol. 2016;113:789-795. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.