Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis.

Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P = .003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P < .0001) and overall survival (P = .0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma.

Training for laparoscopic pancreaticoduodenectomy.

In recent years, laparoscopic procedures have developed rapidly, and the reports of laparoscopic pancreatic resection including laparoscopic pancreaticoduodenectomy (LPD) have increased in number. Although LPD is a complex procedure with high mortality, the training system for LPD remains unestablished. Ensuring patient safety is extremely important, even in challenging surgeries such a LPD. At present, several tools have been developed for surgical education to ensure patient safety preoperatively, such as video learning, virtual reality simulators, and cadaver training. Although LPD is reported as a safe and feasible choice, LPD is still a challenging operation. An LPD training system should be established with a board-certified system.

Predictors of portal and splenic vein thrombosis after laparoscopic splenectomy: a retrospective analysis of a single-center experience.

PURPOSE: Laparoscopic splenectomy (LS) has become the standard operative approach for splenectomy. Portal or splenic vein thrombosis (PSVT) is a serious and common complication after LS, and lethal complications of PSVT can occur when the portal vein is completely occluded by portal vein thrombosis (PVT). We aimed to clarify the predictors of PSVT after LS and to determine which of them were also predictors of PVT. METHODS: A total of 56 consecutive patients who underwent elective LS were enrolled in this study. The patients were divided into two groups based on the presence or absence of PSVT after LS. In addition, patients with PSVT were divided into two groups: a PVT group and a non-PVT group. The preoperative and intraoperative clinical data were compared among the groups. RESULTS: Thirty (53.6%) patients developed PSVT. The splenic vein diameter was the most useful predictor for the development of PSVT, and 10 mm was an accurate splenic vein diameter cut-off value for use as a predictive factor for PSVT. In addition, the splenic vein diameter was the most useful predictor of the development of PVT from splenic vein thrombosis (SVT), and 14 mm was found to be an accurate cut-off value. CONCLUSION: PSVT is a common postoperative complication that is identified on enhanced computed tomography. The splenic vein diameter is not only a predictor of PSVT but also of the development of PVT from SVT.

Prognostic Impact of Preoperative Lymph Node Enlargement in Intrahepatic Cholangiocarcinoma: A Multi-Institutional Study by the Kyushu Study Group of Liver Surgery.

BACKGROUND: Although lymph node metastasis (LNM) has been considered an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), the impact of lymph node enlargement on the prognosis of ICC, and the accuracy of diagnosis of LNM, have not been fully clarified. METHODS: Using a chart review of 225 patients with ICC, we compared survival times between patients with and without lymph node enlargement, and we evaluated the accuracy of diagnosis of LNM. We also performed a multivariate analysis to determine the variables affecting overall survival in the study population. RESULTS: The survival time of patients without lymph node enlargement was significantly longer than that of patients with lymph node enlargement (median survival time [MST] 43.7 vs. 20.1 months; p = 0.007). However, in the group with enlarged lymph nodes, survival time was prolonged as a result of hepatectomy (MST 20.1 vs. 7.6 months; p < 0.01). The sensitivity of lymph node size and positron emission tomography-computed tomography findings for diagnosing LNM were 50.0 % (23/46) and 31.2 % (5/16), respectively, and were thus insufficient. Multivariate analysis identified the serum carcinoembryonic antigen (hazard ratio [HR] 1.830) and carbohydrate antigen 19-9 (HR 2.189) levels, blood transfusion (HR 1.792), intrahepatic metastasis (HR 1.988), and final stage (HR 8.684) as prognostic factors for overall survival, but lymph node enlargement was not identified as a prognostic factor. CONCLUSION: Preoperative evaluation of LNM proved to be difficult, and survival time in ICC patients with lymph node enlargement was prolonged as a result of hepatectomy. Thus, ICC patients with preoperative lymph node enlargement should not be prematurely deemed non-curative cases.

Vitamin D binding protein-macrophage activating factor inhibits HCC in SCID mice.

BACKGROUND: A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC. METHODS: The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d. RESULTS: DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group. CONCLUSION: DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC.

Diverse effects of FK506 on the apoptosis of hepatocytes and infiltrating lymphocytes in an allografted rat liver.

BACKGROUND: The current study investigated whether FK506 (FK) regulates the apoptotic systems in allografted rat liver and the contribution of Fas/Fas-ligand system and Bcl-2 family during acute rejection. MATERIALS AND METHODS: The recipients were divided into three groups, the allo, the allo-FK, and the syn group. Rats were euthanized 1, 3, 5, and 7 d after OLT. Apoptotic activity was explored using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression of Fas/Fas-ligand and Bcl-2/Bax in the grafted livers was investigated by Western blotting and immunohistochemistry. RESULTS: The apoptotic index (AI) of hepatocytes in the allo-FK group was less than that in the allo group. Fas in the allo group was more intense than that in the allo-FK group in the periportal areas on day 1 and 3, while Bcl-2 in the allo group was less intense than that in the allo-FK group in the pericaval areas at all time-points after OLT. CONCLUSION: FK provides beneficial antiapoptotic effects on hepatocytes in the grafted rat livers through both the down-regulation of Fas expression in the periportal areas and the up-regulation of Bcl-2 expression in the pericaval areas.

A case of lupus-associated pancreatitis with ruptured pseudoaneurysms.

Pancreatitis is a relatively rare complication in systemic lupus erythematosus (SLE). Herein we report a case of SLE with the initial development of acute pancreatitis, subsequently complicated by bleeding pseudoaneurysms. A 55-year-old Japanese woman was admitted to our hospital for the treatment of SLE. During the course of treatment, she complained of upper abdominal pain. An abdominal computed tomography (CT) scan showed that the pancreas was diffusely enlarged, and she was diagnosed with acute pancreatitis. Her pancreatitis was resistant to glucocorticoid therapy and was subsequently associated with pancreatic pseudocysts and recurrent rupture of the pseudoaneurysms. After surgical drainage of the hemorrhagic pseudocysts, the patient's clinical condition gradually improved with intensive therapies. Our case indicates that lupus pancreatitis can be associated with the potentially fatal complication of recurrent bleeding of pseudoaneurysms.

S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

[A case of ectopic hepatocellular carcinoma].

A 47-year-old otherwise healthy woman, presented elevation of alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. A screening abdominal CT revealed no abnormal change. An abdominal MRI and repeated CT, however, revealed a 20-mm tumor adjacent to the inferior vena cava and adjacent to or involving the liver. A surgical resection of the tumor was performed. The tumor was adjacent to, but distinct from, the liver. The Capsule of the tumor was connected to the liver but it was distinct from hepatic, renal, and adrenal tissue. A histological examination yielded a diagnosis of moderately differentiated hepatocellular carcinoma, with positive staining of hepatocyte-specific antigen and AFP.

The Feasibility and Efficacy of Laparoscopic Extended Total Mesorectal Excision for Locally Advanced Lower Rectal Cancer.

BACKGROUND/AIM: Extended total mesorectal excision (ETME) is defined as en bloc resection of the adjacent organs outside the mesorectal fascia, that is indicated in cases with locally advanced lower rectal cancer (T4 tumor). The aim of this study was to evaluate the clinical and oncological outcomes of laparoscopic ETME (L-ETME) for locally advanced lower rectal cancer. PATIENTS AND METHODS: The present study analyzed clinical outcomes and oncological outcomes of 11 consecutive patients who underwent L-ETME for cT4 lower rectal cancer in Nagasaki Medical Center between 2012 and 2015. RESULTS: Of the 11 patients, 7 underwent neoadjuvant therapy, and 7 underwent pelvic node dissection. One case (7.1%) underwent resection of anterior organs (prostate), 6 cases (54.5%) had resection of the lateral organs (neurovascular bundle, hypogastric nerve, pelvic plexus, ovary, and internal iliac blood vessels) and 4 cases (36.4%) had resection of both anterior and lateral organs. In all cases enrolled in this study, R0 resection was achieved. The median operation time and intraoperative blood loss were 416 min and 350 ml, respectively. The postoperative complication rate was 18.2% (2/11). The 3-year overall survival rate was 79.5%, and the 3-year local recurrence-free survival rate was 87.5%. There was no mortality and no re-operation in this series. CONCLUSION: The results of the present study suggest that L-ETME is feasible and has efficacy for locally advanced lower rectal cancer.

Adherence to Adjuvant Endocrine Therapy in Women With Breast Cancer: A Prospective Observational Study in Japanese Women.

INTRODUCTION: Nonadherence to adjuvant endocrine therapy has been poorly studied in Asian patients with breast cancer. We therefore assessed adherence to endocrine therapy among women with breast cancer in Japan. PATIENTS AND METHODS: We conducted a prospective observational study among Japanese women with hormone receptor-positive breast cancer. Patients brought their pill packets to visits for 1 year and answered a questionnaire. We also examined prescription records during the study period. Adherence to endocrine therapy was defined as patients who had taken > 80% of the pills according to the packets during the study. Clinicopathologic features and questionnaires were compared between adherent and nonadherent patients. RESULTS: A total of 234 patients completed the trial, of whom 85% demonstrated adherence based on pill packets, and 98% demonstrated adherence based on prescription records. Mastectomy, higher stage, nodal metastasis and adjuvant chemotherapy were correlated with adherence based on pill packets. Adjuvant chemotherapy was an independent factor associated with adherence. According to the questionnaire, adherent patients were more likely to consult a nurse when they had trouble with their medication. These patients also emphasized the efficacy rather than the side effects of the medication. Nonadherent patients were aware that they were being nonadherent. CONCLUSION: The results of this study revealed that 85% of patients were adherent to endocrine therapy, but physicians were unaware of the nonadherent patients. Raised awareness of nonadherence and information sharing between patients and medical teams might increase adherence to endocrine therapy.

Human intrahepatic biliary epithelial cell as a possible modulator of hepatic regeneration: Potential role of biliary epithelial cell for hepatic remodeling in vivo.

BACKGROUND: During liver regeneration, the process of hepatic wound healing, a complex cascade of inflammatory signals, recruit inflammatory cells, stimulate hepatobiliary cell proliferation, direct cell migration and induce vascularization to restore tissue integrity, irrespective of its etiology. This might also be the case in cholangiopathies, in which the initial target is the branch of the intrahepatic biliary tree; that is, primary biliary cirrhosis. Previous studies about biliary wound healing focused mainly on the inducers of compensatory biliary proliferation following bile duct insult. Nevertheless, the microenvironment around biliary wound healing responses, which in turn might affect hepatic remodeling, possibly by biliary epithelial cells themselves via paracrine manner, is still less known. METHODS: In this study, we defined the humoral factors that are released from human intrahepatic biliary epithelial cell lines (HIBEC) with human cytokine array, and reviewed their relevance according to the previous published work. RESULTS: Conditioned medium of HIBEC were revealed to be rich in multiple cytokines and chemokines, including ELR(+)CXC chemokines, such as interleukin-8/CXCL8, growth-related oncoprotein (GRO), epithelial neutrophil chemoattractant (ENA-78), known chemoattractants with a wide range of non-leukocytic activities. Subsequent enzyme-linked immunosorbent assay analyses confirmed that the secretion was commonly observed in various culture conditions and in both an apical and basolateral direction. CONCLUSIONS: Considering that some of these factors had been already reported to have direct autocrine mitogenic influence on HIBEC, these findings could further strengthen an active role of HIBEC as a modulator of hepatic regeneration, through its biological reactivity on inflamed milieu.

Clinical and Oncological Outcomes of Laparoscopic Lateral Pelvic Lymph Node Dissection in Advanced Lower Rectal Cancer: Single-institution Experience.

AIM: The aim of this study was to compare the clinical outcomes of laparoscopic versus open surgery for total mesorectal excision (TME) with lateral pelvic lymph node dissection (LPLD) in advanced lower rectal cancer. PATIENTS AND METHODS: Forty-four patients who underwent TME with LPLD for lower rectal cancer (pStage II/III) between January 2008 and December 2014 were divided into two groups according to the type of surgical approach as follows: open LPLD group (OLD, n=17) and laparoscopic LPLD group (LLD, n=27). RESULTS: Operative time was comparable between the groups (p=0.15), whereas intraoperative blood loss and complication rates were significantly less in LLD than in OLD. Postoperative hospital stay was shorter in LLD than in OLD. Overall survival and local recurrence-free survival were similar in the two groups. Disease-free survival was better in LLD than in OLD, although the difference was not significant. CONCLUSION: Laparoscopic TME with LPLD is safe and feasible.

The long-term survival in primary retroperitoneal mucinous cystadenocarcinoma: a case report.

BACKGROUND: Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is extremely rare, and its biological behavior, pathogenesis, optimum treatments, and prognosis remain to be elucidated. We herein report a case of PRMC with an 80-month follow-up. CASE PRESENTATION: A 29-year-old woman was diagnosed with unknown retroperitoneal tumor with benign right ovarian cyst and uterine fibroids, and she underwent laparotomy. The tumor was completely resected with a subsequent histopathological diagnosis of primary retroperitoneal mucinous cystadenocarcinoma (PRMC). Eighty months after surgery, she remains recurrence-free. CONCLUSION: PRMC is an extremely rare tumor. Only around 60 cases have so far been published in the literature. The preoperative diagnosis of PRMC is difficult, and a definitive diagnosis can usually only be made based on the findings of histopathological examinations after surgery. Presently, only radical resection is useful for both diagnostic and therapeutic purposes. The optimal long-term management after surgery is still not well established. Further studies on PRMC are therefore needed to elucidate the etiology and establish effective treatments.

A case of single incision laparoscopic total colectomy for intestinal neuronal dysplasia type B.

INTRODUCTION: Intestinal neuronal dysplasia type B (IND-B) is an infrequent disease of the submucosal plexus of intestine manifesting chronic intestinal obstruction or severe chronic constipation. IND is rarely reported in adult patients. PRESENTATION OF A CASE: The present study reports on the case of a 36 year-old woman suffering from longstanding chronic constipation and who was diagnosed with severe constipation in more than 20 years. Although she began to take a large amount of stimulant laxatives, such as "senna" and "bisacodyl", constipation symptoms did not improve, she was admitted to our hospital. It was diagnosed with refractory constipation of the medication treatment-resistance, total colectomy with ileorectal anastomosis by single incision laparoscopic surgery (SILS) was performed. The final pathological diagnosis was IND-B. DISCUSSION: Refractory constipation after medical treatment is often seen in young generation. SILS has benefits of better cosmesis, reduced morbidity, reduced postoperative pain, and reduced length of hospital stay. CONCLUSION: For the patients with refractory constipation associated with neuropathy such as IND, total colectomy by SILS was very effective.

Anterior approach for right hepatectomy with hanging maneuver for hepatocellular carcinoma: a multi-institutional propensity score-matching study.

BACKGROUND: This multi-institutional study aimed to assess the benefits of anterior approach for right hepatectomy with hanging maneuver (ARH-HM) for hepatocellular carcinoma (HCC) compared with conventional right hepatectomy (CRH). METHODS: From January 2000 to December 2012, 306 patients with HCC ≥5 cm were divided into two groups: ARH-HM (n = 104) and CRH (n = 202). RESULTS: After one-to-one propensity score-matched analysis, 72 ARH-HM and 72 CRH patients presented comparable background factors. Patients in the ARH-HM group demonstrated significantly less intraoperative blood loss (480 vs. 1,242 g, P < 0.001) and a lower frequency of red cell concentrate transfusion (21.1% vs. 50.7%, P < 0.001) compared with patients in the CRH group. The 5-year overall survival rate was significantly better in the ARH-HM group compared with the CRH group (50.2% vs. 31.4%, P = 0.021). Limited to patients with HCC ≥10 cm, recurrence-free and overall survival of the ARH-HM group was significantly greater than those of the CRH group. CONCLUSION: In comparison with CRH, ARH-HM for large HCC can provide better overall survival rates with a decrease in intraoperative blood loss and transfusion rates. Survival impact was evident especially in patients with HCC ≥10 cm.

Surgical management of recurrent intrahepatic cholangiocarcinoma: predictors, adjuvant chemotherapy, and surgical therapy for recurrence: A multi-institutional study by the Kyushu Study Group of Liver Surgery.

Objectives of the present study were to identify predictors of the recurrence of intrahepatic cholangiocarcinoma (ICC), and to evaluate the survival benefit of adjuvant chemotherapy and surgical treatment for ICC recurrence. A multi-institutional retrospective study was carried out in 356 patients with ICC who underwent curative surgery at one of 14 institutions belonging to the Kyushu Study Group of Liver Surgery. A total of 214 patients (60%) had recurrence. Predictors of ICC recurrence were as follows: positive for pathological intrahepatic metastasis (im), positive for lymph node metastasis (n), positive for pathological lymphatic infiltration (ly), pathological bile duct invasion (b), and tumor size ≥4.4 cm. Adjuvant chemotherapy was given to 120 patients (34%) and, in the patients with im or tumor size ≥4.4 cm, adjuvant chemotherapy showed a survival benefit. Only 37 patients (17%) underwent surgical treatment for ICC recurrence. The surgical treatment resulted in a good 5-year survival rate (44%), which is similar to the rate obtained by the first operation for primary ICC. Prognosis of patients with primary im after the second operation was significantly worse (5-year survival 18%) compared to patients without primary im. Primary im+ should be considered a contraindication for surgical treatment for ICC recurrence.

Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: Comparative analysis after propensity score matching: A multicenter study.

BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. METHODS: This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. In total, 173 patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by curative surgery from 1994 to 2008 were evaluated. Clinicopathologic features and adverse events were compared between patients who underwent TT and those who underwent TL. After adjustment for differences in baseline clinicopathologic factors using propensity score matching, we compared recurrence-free survival (RFS) and OS. RESULTS: TL was performed in 120 patients and TT in 53 patients. Patients who underwent TT were older; had larger tumors; more frequently had nodal metastasis, multifocal tumors, and extracapsular invasion; and more frequently underwent radioactive iodine ablation than patients who underwent TL. Hypocalcemia requiring medication and recurrent laryngeal nerve paralysis were more frequent in TT than TL. The 10-year RFS and OS of all patients were 93.3% and 96.7%, respectively. There was no significant difference in RFS (90.6% vs 93.0% in TT and TL groups, respectively) or OS (96.2% vs 96.9% in TT and TL groups, respectively) according to the extent of surgical resection after propensity score matching. CONCLUSION: Equivalent prognoses were observed for patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by TL or TT after propensity score matching. Adverse events occurred less frequently in patients who underwent TL than TT.

Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs.

AIM: To characterize and evaluate the therapeutic efficacy of bioartificial liver (BAL) as compared to that of continuous hemodiafiltration (CHDF) with plasma exchange (PE), which is the current standard therapy for fulminant hepatic failure (FHF) in Japan. METHODS: Pigs with hepatic devascularization were divided into three groups: (1) a non-treatment group (NT; n = 4); (2) a BAL treatment group (BAL; n = 4), (3) a PE + CHDF treatment group using 1.5 L of normal porcine plasma with CHDF (PE + CHDF, n = 4). Our BAL system consisted of a hollow fiber module with 0.2 mum pores and 1 multiply 10(10) of microcarrier-attached hepatocytes inoculated into the extra-fiber space. Each treatment was initiated 4 h after hepatic devascularization. RESULTS: The pigs in the BAL and the PE + CHDF groups survived longer than those in the NT group. The elimination capacity of blood ammonia by both BAL and PE + CHDF was significantly higher than that in NT. Aromatic amino acids (AAA) were selectively eliminated by BAL, whereas both AAA and branched chain amino acids, which are beneficial for life, were eliminated by PE + CHDF. Electrolytes maintenance and acid-base balance were better in the CPE + CHDF group than that in the BAL group. CONCLUSION: Our results suggest that PE + CHDF eliminate all factors regardless of benefits, whereas BAL selectively metabolizes toxic factors such as AAA. However since PE + CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE + CHDF might be more effective for FHF.