Risk Factors for and Outcomes of Intraoperative Blood Loss in Liver Resection for Hepatocellular Tumors.

Intraoperative blood loss (IBL) during liver resection is a predictor of morbidity, mortality, and tumor recurrence after hepatectomy; however, there have been few reports on patient factors associated with increased IBL. We enrolled consecutive patients who underwent liver resection for primary liver malignancies, and evaluated the predictors of IBL using a data set in which factors that might influence IBL, such as surgical devices, methods and anesthetic technique, were all standardized. We studied 244 patients. A multivariate analysis revealed that higher IBL was an independent risk factor for post-hepatectomy liver failure grade ≥B and overall survival. Multiple linear regression analyses showed serum creatinine, clinically significant portal hypertension (CSPH), tumor size, and major hepatectomy were all significant predictors of IBL. In conclusion, higher IBL was significantly associated with increased morbidity and mortality in patients with primary HCC who underwent liver resection. The risk of IBL was related to several factors including tumor size, serum creatinine, CSPH, and major hepatectomy.

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. RESULTS: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. CONCLUSIONS: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.

Large surgically resected leiomyosarcoma of the liver: a case report.

BACKGROUND: Primary hepatic leiomyosarcoma (PHL) is an extremely rare type of tumor. We herein report a case of a large surgically resected leiomyosarcoma of the liver. CASE PRESENTATION: A 69-year-old man with a feeling of epigastric compression was referred for examination of an abdominal mass. He had no history of liver disease or alcohol abuse. Liver function tests indicated Child-Pugh class A. Tumor markers were negative. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a relatively well-contrasted 12 × 11 × 8 cm tumor with well-defined boundary replacing the lateral segment of the liver alongside multiple intrahepatic metastases. Several nodules up to 12 mm were found in both lungs, suggestive of metastasis. SUVmax of the liver mass and lung tumor in positron emission tomography were 10.4 and 1.5, respectively. Hepatocellular carcinoma was primarily suspected. Lateral segmentectomy of the liver was performed to confirm diagnosis and prevent tumor rupture. Macroscopically, the lateral segment of the liver had been replaced by a lobular or multinodular tumor with a maximum diameter of 15 cm. In pathological findings, the tumor consisted of bundle-like proliferation of complicated banding spindle-like cells with clear cytoplasm, accompanied by storiform pattern and compressed blood vessels. Nuclear fission images were observed in 8/10 HPF. Partial necrosis was present, with associated venous invasion and intrahepatic metastasis. Immunohistochemical staining for tumor cells revealed desmin, α-smooth muscle actin (αSMA), and h-caldesmon were all positive, informing a final diagnosis of PHL. The postoperative course was uneventful, and he was discharged on the 12th postoperative day. CONCLUSIONS: PHL is a rare malignant disease with relatively poor prognosis. To confirm a diagnosis of PHL, immunohistochemical analysis as well as histopathological findings is important. The preferred treatment is surgical resection, sometimes in combination with adjuvant chemotherapy and radiotherapy. Further studies are needed to elucidate and better understand this uncommon clinical entity.

Efficacy of Neoadjuvant Chemotherapy in Distal Pancreatectomy with En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer.

BACKGROUNDS: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. METHODS: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. RESULTS: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). CONCLUSION: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy.

Elevation of Mac-2 binding protein glycosylation isomer after hepatectomy is associated with post-hepatectomy liver failure, total Pringle time, and renal dysfunction.

BACKGROUND: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker used to assess liver fibrosis. However, it has been reported that M2BPGi is likely to reflect other factors not limited to liver fibrosis. METHODS: We retrospectively analyzed 79 patients with liver tumors who underwent liver resection. M2BPGi was measured within 1 week before operation and almost 1 month after operation. We introduced a value termed the "ΔM2BPGi ratio" (=M2BPGiafter operation/M2BPGibefore operation), and analyzed factors that influenced the ΔM2BPGi ratio. RESULTS: The median value of the ΔM2BPGi ratio was 1.28 (range, 0.36-5.68). In 64 patients (81.0%), the cutoff index values of M2BPGi were elevated approximately 1 month after operation, especially in patients who experienced post-hepatectomy liver failure (PHLF). Multiple linear regression showed total Pringle time, PHLF grade ≥B, and preoperative value of creatinine were significant predictors of the ΔM2BPGi ratio. The mean values of the ΔM2BPGi ratio were 1.37 ± 0.07, 1.52 ± 0.22, and 2.94 ± 0.30 for PHLF grade 0, grade A, and grade B, respectively, resulting in statistically significant differences by the Kruskal-Wallis test (P = 0.022). CONCLUSIONS: Total Pringle time, PHLF grade ≥B, and preoperative creatinine significantly influenced the elevation of M2BPGi almost 1 month after liver resection. This study strongly affirms the previous suggestion that M2BPGi is likely to reflect other factors not limited to liver fibrosis.

Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction.

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases.

A case of primary gastric undifferentiated high-grade pleomorphic sarcoma diagnosed with chief complaint of fever: a case report and literature review.

BACKGROUND: Undifferentiated high-grade pleomorphic sarcoma in gastrointestinal tract is extremely rare, and its prognosis is poor. CASE PRESENTATION: An 82-year-old man visited a previous hospital complaining of fever, general fatigue, and shaking chill, for which he received antibiotics therapy. As the fever continued, he was referred to our hospital, where computed tomography and upper gastrointestinal endoscopy showed a 6-cm gastric tumor. A preoperative biopsy was consistent with a malignant mesenchymal tumor, but could not provide a definitive pathological diagnosis nor prove a cause-and-effect relationship between the chief complaint and the gastric tumor. The gastric tumor had grown to 8 cm in diameter within a month so we performed a partial gastrectomy. The pathological postoperative diagnosis was undifferentiated high-grade pleomorphic sarcoma that produced granulocyte colony-stimulating factor. The patient's fever quickly improved, and he showed a good postoperative course. CONCLUSIONS: We herein report a case of rapidly growing, undifferentiated, high-grade pleomorphic gastric sarcoma, which presented as a chief complaint of fever.

[A Case of Virchow's Lymph Node Recurrence of Gastric Cancer Who Had Underwent Gastrectomy, and Treated with S-1 Monotherapy Leading to Complete Response (CR)].

We report the case of a 67-year-old male with Virchow's lymph node recurrence of gastric cancer, who underwent distal gastrectomy for type 2 forecourt part of pylorus gastric cancer, showing complete response(CR)in response to S-1 monotherapy. The tumor was pathologically diagnosed as Stage IIIb(well to poorly differentiated adenocarcinoma, T3[SE], N2 [20/51], M0). Virchow's lymph node metastasis was confirmed 2 months after surgery. One week after S-1 administration, a reduction in lymph node size was observed. After 5 courses of S-1 monotherapy, he achieved CR. The patient maintained CR for 2 years, before we switched to uracil and tegafur(UFT)monotherapy. The patient maintained CR for 2 years, after which UFT was discontinued. No relapse was observed 22 months after discontinuation.

Gastrointestinal bleeding and blood transfusion in the elderly in Japan.

BACKGROUND/AIMS: The incidence of gastrointestinal bleeding (GIB) increases with age and blood transfusion is frequently given for the management of GIB. In this report, we summarized our data of the patients with GIB and discussed the relationship between blood transfusion and age in patients with GIB. METHODOLOGY: The patients were divided into two groups according to age, following elderly (≥75 years old) and younger (<75 years old) group. The causes and clinical outcome (blood transfusions, management) of each group were compared. RESULTS: One-hundred and twenty patients with GIB were hospitalized (59 men, 61 women) with a mean age of 72.0±15.8 years (range 16-96 years old). Thirty-one patients (25.8%) received blood transfusion. The mean pre-transfusion hemoglobin was 6.4±1.2g/dL (elderly 6.3±1.4, younger 6.6±1.0g/dL) and the mean amount of blood transfusion was 2.8±1.6U (elderly 3.2±1.8, younger 2.3±0.9U). The elderly patients using antithrombotic drugs need greater amounts of blood transfusion than younger patients using antithrombotic drugs. The hemoglobin level of the elder patients without antithrombotic drugs was significantly lower than that of younger patients without antithrombotic drugs. CONCLUSIONS: Our data suggest that our blood transfusion strategy seems to be in tolerance level with restrictive blood transfusion strategy.

Gastrointestinal bleeding associated with antithrombotic therapy in the elderly in Japan.

BACKGROUND/AIMS: We summarize data of patients with gastrointestinal bleeding (GIB) and discuss the relationship between antithrombotic drug use and age in patients with GIB. METHODOLOGY: One-hundred and twenty patients with GIB were divided into two groups according to age (=75 years old and <75 years old). The causes and clinical outcome of each group were compared. RESULTS: Forty-two patients received antithrombotic therapy. The main antithrombotic drugs were low dose aspirin (38 patients), ticlopidine (5 patients) and warfarin (3 patients). Compared with younger GIB patients, elderly patients had more coexisting illness and antithrombotic drugs. In patients taking antithrombotic drugs, upper GIB is more frequent than those not taking antithrombotic drugs (p<0.05) and antithrombotic drugs were the risk for GIB from erosive lesions of the esophagus or stomach. In the lower gastrointestinal tract, there was no difference of incidence related to antithrombotic use. The initial endoscopic hemostasis was performed in 14 patients. Eight varices patients received endoscopic vanding and 6 of 43 gastroduodenal ulcer patients had mechanical clip hemostasis. CONCLUSIONS: From our findings, antithrombotic drugs were considered to be a risk for GIB. It might be important to prevent or minimize GIB in elderly patients prescribed antithrombotic drugs.

Long-term surviving patient with inferior vena cava tumor thrombus and extrahepatic metastasis after spontaneous ruptured hepatocellular carcinoma.

We present a case of long-term survival in a patient with inferior vena cava tumor thrombus (IVCTT) and extrahepatic metastasis after resection for spontaneous ruptured hepatocellular carcinoma (HCC). The patient was a 73-year-old Japanese man previously diagnosed with chronic hepatitis B. He was referred to our emergency room and diagnosed with spontaneous ruptured HCC. The patient was immediately treated with transcatheter arterial embolization, and we then performed second-stage hepatic resection 50 days later. Although des-gamma-carboxy prothrombin was reduced to a normal level after hepatectomy, it gradually increased and computed tomography showed a disseminated tumor in the diaphragm near S2 of the liver with IVCTT and right atrium tumor thrombus. Recurrent HCC was treated with monthly transcatheter arterial infusion chemotherapy (TAI) and conformal radiotherapy (RT) of 40 Gy. After TAI and RT procedures, the disseminated tumor and IVCTT completely disappeared. Four years after TAI and RT procedures, the tumors were well controlled with no local recurrence. About 6-7 years after spontaneous ruptured HCC, lung metastasis and spleen metastasis were detected and resected, respectively. The patient is still alive and doing well over 7 years after spontaneous ruptured HCC.

Immunohistochemical Examination of a Resected Advanced Hilar Cholangiocarcinoma Arising in a 29-Year-Old Male without Primary Sclerosing Cholangitis.

A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9) level was elevated to 939 IU/l, and the pathological findings revealed moderately differentiated tubular adenocarcinoma which involved almost the entire thickness of the hepatic duct and the adjacent liver tissue (T3) and which was associated with lymph node metastasis (N1). It was a stage IIB (T3N1M0) tubular adenocarcinoma according to UICC pathological staging. Immunohistochemical examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3-3sigma and p27 were negative. The pathological and immunohistochemical findings indicated high malignant potential indicating poor prognosis. We administrated the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient is alive without recurrence and doing well two years after surgery. We also review other reports of cholangiocarcinoma patients aged less than 30 years.

Significance of DNA polymerase delta catalytic subunit p125 induced by mutant p53 in the invasive potential of human hepatocellular carcinoma.

OBJECTIVE: To clarify the role of DNA polymerase delta in tumor progression, we examined the expression of its main catalytic subunit p125 encoded by POLD1 in hepatocellular carcinoma (HCC) and human HCC cell lines. METHODS: We examined the expression of p53 and p125 in HCC by using immunohistochemistry and Western blotting. Characteristic changes observed in human HCC cell lines after transfection were examined. RESULTS: Immunohistochemical examination revealed positive staining of p125 in HCC cell nuclei, but few positively stained cells were observed in noncancerous tissues (p < 0.0001). p125 expression in specimens significantly correlated with cellular differentiation (p = 0.0048) and the degree of vascular invasion (p = 0.0401). It also significantly correlated with abnormal p53 expression. In vivo studies showed that p125 was upregulated in mutant p53-transfected HepG2 cells, which had more invasive potential than did control cells. Furthermore, the expression and invasive potential were reduced by the silencer sequence for POLD1. CONCLUSIONS: These findings suggest that the DNA polymerase delta catalytic subunit p125 induced by mutant type p53 plays an important role in tumor invasion, which leads to a poorer prognosis in HCC.

Dual hepatic artery reconstruction in living donor liver transplantation using a left hepatic graft with 2 hepatic arterial stumps.

BACKGROUND: A left hepatic graft in living donor liver transplantation (LDLT) often has 2 thin and short hepatic arterial stumps, which makes hepatic artery (HA) reconstructions much more difficult to perform. Consequently, some investigators regard using a left graft as a contraindication to LDLT, whereas others report that the reconstruction of only 1 HA is sufficient for most LDLTs. The aim of this retrospective study was to investigate whether 2 HAs on a left hepatic graft in an LDLT can be reconstructed safely and whether the outcomes of LDLTs are affected by reconstructing both HAs (dual reconstruction). METHODS: A total of 175 LDLTs using a left graft between October 1996 and April 2008 were divided into 3 groups: group 1 (n = 104): 1 HA stump with 1 HA reconstruction; group 2 (n = 47): 2 HA stumps with dual HA reconstruction; and group 3 (n = 24): 2 HA stumps with only 1 HA reconstruction. We reconstructed HAs using microvascular surgical techniques. RESULTS: With technical advancement, we have been able to reconstruct both HAs in most cases without any HA-related complications, despite the fact that complex HA reconstructions were needed. Group 3 patients had a significantly greater incidence of anastomotic biliary stricture, which was decreased by dual HA reconstructions to the same level as observed in group 1. CONCLUSION: Dual HA reconstructions can be performed safely in LDLTs with a decreased incidence of anastomotic biliary stricture.

New prediction factors of small-for-size syndrome in living donor adult liver transplantation for chronic liver disease.

Small-for-size syndrome (SFSS), which is characterized by synthetic dysfunction and prolonged cholestasis, is a major cause of worse short-term prognoses after living donor adult liver transplantation (LDALT). However, the risks of SFSS remain unclear. The aim of this study was to clarify the risks of SFSS, which were analysed in 172 patients who underwent LDALT for chronic liver disease. Graft types included left lobe with caudate lobe graft (n = 110) and right lobe graft (n = 62). Thirty-four cases (24 with left lobe grafts and 10 with right lobe grafts) were determined as SFSS. SFSS developed even if the actual graft-to-recipient standard liver volume ratio was >40%. Logistic regression analysis revealed three independent factors associated with SFSS development in left and right lobe grafts: donor age, actual graft-to-recipient native liver volume ratio, and Child's score. Donor age and actual graft-to-recipient native liver volume ratio may become predictive factors for SFSS development in left and right lobe grafts in patients undergoing LDALT.

Phase I/II study of the lipiodolization using DDP-H (CDDP powder; IA-call(®)) in patients with unresectable hepatocellular carcinoma.

PURPOSE: Lipiodol Ultra-Fluid (Lipiodol(®)), an oily contrast medium, is selectively retained in hepatocellular carcinoma (HCC) through hepatic arterial infusion. DDP-H (IA-call(®)) developed as a CDDP powder, and may be a possible chemotherapeutic agent with lipiodol. We carried out a phase I/II study of the lipiodolization using DPP-H in patients with unresectable HCC. METHODS: Phase I and pharmacokinetic study: The dose-limiting toxicity (DLT), the maximum tolerance dose (MTD), and the recommended dose (RD) were determined using a modified Fibonacci scheme. The concentration-time profile of total platinum in plasma was analyzed. Phase II study: Thirty-five patients with unresectable HCC received lipiodolization using DDP-H under RD, and the efficacy and safety were assessed. RESULTS: DLT was grade 3 vomiting at 40 mg/m(2). Therefore, MTD and RD were 35 mg/m(2). The peak of total platinum in plasma was over 1.0 µg/ml at 40 mg/m(2) at 30 min after infusion. Of the 35 patients, 16 (45.7%) demonstrated complete responses, and 4 (11.4%) demonstrated partial responses with an additional 9 patients (25.7%) having stable diseases, as assessed by RECIST. Grade 3 thrombocytopenia was found in 1 patient (2.9%), grade 2 hyperbilirubinemia was found in 2 patients (5.7%), and grade 2 vomiting was found in 4 patients (11.4%). CONCLUSION: Lipiodolization using DDP-H at 35 mg/m(2) is effective and well tolerated in patients with unresectable HCC.

Fascin expression in progression and prognosis of hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Fascin is an actin-bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry. METHODS: A total of 137 patients with HCC were stained with anti-fascin antibody. The tumor cells having unequivocal cytoplasmic and/or membranous fascin immunoreactivity were defined as fascin-positive. RESULTS: Immunohistochemically, 23 (16.8%) HCCs having unequivocal fascin immunoreactivity were found. Tumors showing fascin expression were larger and less differentiated than those showing no fascin expression (P = 0.0239 and 0.0018, respectively). Portal venous invasion, bile duct invasion, and intrahepatic metastasis were detected significantly more frequently in fascin-positive group (P = 0.0029, 0.0333, and 0.0403, respectively). In addition, high alpha-fetoprotein (AFP) levels were significantly associated with the fascin expression in HCC (P = 0.0116). Fascin-positive group had significantly poorer outcomes than fascin-negative group and was an independent prognostic factor for disease-free survival. CONCLUSIONS: Fascin might become a novel marker of progression in HCC and a significant indicator of a poor prognosis for patients with HCC.

Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan.

BACKGROUND: A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. METHODS: A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. RESULTS: The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). CONCLUSIONS: Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.

Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation.

BACKGROUND: Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. METHODS AND RESULTS: A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). CONCLUSIONS: A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC.

Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C.

BACKGROUND: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. MATERIALS AND METHODS: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. RESULTS: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. CONCLUSION: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients.