Depletion of proteasome subunit PSMD1 induces cancer cell death via protein ubiquitination and DNA damage, irrespective of p53 status.

Hepatocellular carcinoma (HCC) is characterized by high incidence and fatality rates worldwide. In our exploration of prognostic factors in HCC, the 26s proteasome subunit, non-ATPase 1 (PSMD1) protein emerged as a significant contributor, demonstrating its potential as a therapeutic target in this aggressive cancer. PSMD1 is a subunit of the 19S regulatory particle in the 26S proteasome complex; the 19S particle controls the deubiquitination of ubiquitinated proteins, which are then degraded by the proteolytic activity of the complex. Proteasome-targeting in cancer therapy has received significant attention because of its practical application as an established anticancer agent. We investigated whether PSMD1 plays a critical role in cancer owing to its prognostic significance. PSMD1 depletion induced cell cycle arrest in G2/M phase, DNA damage and apoptosis of cancer cells, irrespective of the p53 status. PSMD1 depletion-mediated cell death was accompanied by an increase in overall protein ubiquitination. These phenotypes occurred exclusively in cancer cells, with no effects observed in normal cells. These findings indicate that PSMD1 depletion-mediated ubiquitination of cellular proteins induces cell cycle arrest and eventual death in cancer cells, emphasizing PSMD1 as a potential therapeutic target in HCC.

A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

NPFFR2 Contributes to the Malignancy of Hepatocellular Carcinoma Development by Activating RhoA/YAP Signaling.

G protein-coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma.

Prognosis after intrahepatic recurrence in the patients who underwent curative resection for hepatocellular carcinoma.

BACKGROUNDS/AIMS: Intrahepatic recurrence is frequent result after hepatectomy for hepatocellular carcinoma (HCC). We analyzed the clinical results of patients who had the intrahepatic recurrences of HCC after curative surgical resections. METHODS: From January 2009 to December 2016, 320 patients underwent curative surgical resection for HCC in department of Surgery, Korea Cancer Center Hospital. After surgical resection, 155 patients had suffered HCC recurrence during follow-up period. Among them, 122 patients had only intrahepatic recurrence initially, who were included in this retrospective study. We analyzed about the period of the recurrence after surgery, treatment methods for the recurred tumors, and poor prognostic factors for survival after intrahepatic recurrences. RESULTS: Among the 122 patients, 83 patients had recurrence within 24 months after surgery. Thirty-eight patients underwent curative treatment for the recurred tumors (re-resection in 18, radiofrequency ablation in 20 patients). Non-curative treatments were performed in 77 patients (TACE in 68 patients, radiotherapy in 9 patients) and conservative management in 7 patients. Five-year survival rate of patients who underwent curative treatment is 86.4% (p≤0.001). Five-year survival rate of non-curative treatment is 55.7% (p≤0.001), conservative management is 0% (p=0.021). Among the clinical factors, non-curative treatment for recurred tumor, AFP level at the time of recurrence, size of recurred tumor were independent poor prognostic factors for survival after intrahepatic recurrences (p<0.001). CONCLUSIONS: For the patients who had intrahepatic recurrent HCC after surgery, aggressive local treatment can improve the prognosis in selective cases. Further study is necessary to validate this retrospective investigation.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Comparison of the clinical results of surgical resection for extrahepatic cholangiocarcinomas: Hilar cholangiocarcinoma and mid-to-distal cholangiocarcinoma.

BACKGROUNDS/AIMS: Hilar cholangiocarcinomas (HLC) are known to have worse prognoses than mid-to-distal cholangiocarcinomas (CBDC). We analyzed the clinical results of surgical resections for extrahepatic cholangiocarcinomas to validate the differences in the prognoses of HLC and CBDC. METHODS: Two hundred and eighty-one patients underwent curative surgical resections for extrahepatic cholangiocarcinomas at the Department of Surgery in the Korea Cancer Center Hospital. Among them, we analyzed the T2 and T3 patients and compared the clinical results between those with HLC (n=74) and those with CBDC (n=65). RESULTS: The rate of R1 resections was significantly higher in the HLC patients compared to the CBDC patients (31.1% vs 12.3%, p=0.006). The overall survival rate of the T2/T3 patients was lower in the HLC group than in the CBDC group (24.5% vs 51.7, p=0.039). The recurrence-free survival rate was 23.3% in the HCL patients and 50.9% in the CBDC patients (p=0.06). In the subgroup analysis, the survival rates were not different in patients who had lymph node metastases or in patients who underwent R1 resections between the HLC and CBDC patients. Poor independent prognostic factors for the overall and recurrence-free survival rates in the T2/T3 extrahepatic cholangiocarcinoma patients were the presence of lymph node metastases and the hilar locations of tumor. CONCLUSIONS: HLC patients had poorer prognoses than CBDC patients. However, in patients with lymph node metastases, the prognosis was poor and was not different between the HLC and CBDC patients. Other adjuvant treatment methods are needed for extrahepatic cholangiocarcinoma patients with lymph node metastases to improve their prognoses.

TMEM165, a Golgi transmembrane protein, is a novel marker for hepatocellular carcinoma and its depletion impairs invasion activity.

Transmembrane protein 165 (TMEM165), a Golgi protein, functions in ion homeostasis and vesicular trafficking in the Golgi apparatus. While mutations in TMEM165 are known to cause human 'congenital disorders of glycosylation', a recessive autosomal metabolic disease, the potential association of this protein with human cancer development has not been explored to date. In the present study, we revealed that TMEM165 is overexpressed in HCC and its depletion weakens the invasive activity of cancer cells through suppression of matrix metalloproteinase­2 (MMP­2) expression. Levels of TMEM165 mRNA and protein were clearly increased in HCC patient tissues and cell cultures. Quantitative real­time RT­PCR analysis of fresh HCC tissues (n=88) revealed association of TMEM165 overexpression with more frequent macroscopic vascular invasion, microscopic serosal invasion and higher α­fetoprotein levels. Notably, depletion of TMEM165 led to a marked decrease in the invasive activity of two different HCC cell types, Huh7 and SNU475, accompanied by downregulation of MMP­2. Our collective findings clearly indicated that TMEM165 contributed to the progression of HCC by promoting invasive activity, supporting its utility as a novel biomarker and therapeutic target for cancer.

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells.

Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher α-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched non-tumor regions. Consistent with the significant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

Promoter methylation of cysteine dioxygenase type 1: gene silencing and tumorigenesis in hepatocellular carcinoma.

BACKGROUNDS/AIMS: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the CDO1 methylation status and hepatocellular carcinoma (HCC) tumorigenesis was evaluated. METHODS: Using a HCC cell line (SNU423), an in vitro demethylation study was performed to confirm whether promoter methylation causes CDO1 down-regulation. The SNU423 cells transfected with the CDO1 cell function was compared to that of naïve cells. An in vivo study using immunohistochemical staining of HCC specimens that were collected from patients who underwent curative liver resection was also performed. RESULTS: CDO1 was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after CDO1 transfection (p<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of CDO1 (p=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of CDO1 expression was not an independent prognostic factor in this study's population. CONCLUSIONS: These results suggested that methylation down-regulated CDO1 expression in the HCC cells. CDO1 methylation may be a potentially valuable diagnostic biomarker for HCC.

The mitochondrial hinge protein, UQCRH, is a novel prognostic factor for hepatocellular carcinoma.

Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-Meier analysis revealed significantly shorter overall (P = 0.005) and recurrence-free survival (P = 0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the α-fetoprotein (AFP) level. The patient subgroup with higher AFP levels (≥20 ng/mL) exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (<20 ng/mL). Multivariate analysis defined UQCRH as an independent poor prognostic factor. Conclusively, our results indicate that UQCRH overexpression is correlated with poor outcomes of HCC patients. Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH overexpression could be a useful indicator for clinical treatment.

Hepatectomy, combined with intraoperative radiofrequency ablation in patients with multiple hepatocellular carcinomas.

BACKGROUNDS/AIMS: We compared the efficacy and safety of a hepatectomy, combined with intraoperative radiofrequency ablation to those of wider extent hepatectomy, alone, in patients with multiple hepatocellular carcinomas (HCCs). METHODS: Between January 2004 and December 2013, 78 patients with multiple HCCs underwent surgery. 25 patients were treated by hepatectomy, combined with intraoperative radiofrequency ablation (RFA) (group A), and 53 underwent hepatectomy only (group B). We retrospectively analyzed medical records to compare the clinical features of these two groups. RESULTS: Patients in group A had more limited resections (less than 2 segments) than those in group B (p<0.001). Patients in group A also tended to have fewer red blood cell transfusions than those in group B (p=0.060). Liver function- and surgery-related complications occurred only in group B. There were no in-hospital mortalities in both groups. The overall survival and disease-free survival outcomes were not significantly different between groups A and B (p=0.177 and p=0.305, respectively). CONCLUSIONS: Hepatectomy combined with intraoperative RFA could be a safe and effective treatment option for patients with multiple HCCs, comparable to extended hepatectomy alone.

CD44 expression in patients with combined hepatocellular cholangiocarcinoma.

PURPOSE: Combined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis. METHODS: Thirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively. RESULTS: There was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040). CONCLUSION: The expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC.

Prognostic Value of SUVmax Measured by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography in Patients with Gallbladder Cancer.

OBJECTIVE: The aim of this study is to investigate the prognostic value of F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder cancer patients. METHODS: From June 2004 to June 2010, a total of 50 patients with gallbladder cancer who underwent diagnostic staging with F-18 FDG PET/CT following curative or palliative treatments were retrospectively evaluated. For the analysis, all patients were classified by age, sex, maximum standardized uptake value (SUVmax), lymph node (LN) or distant metastasis, serum level of CA19-9 and CEA, type of treatment and American Joint Committee on Cancer (AJCC) stage. RESULTS: The median survival for the 50 patients was 245 days and the median SUVmax in PET/CT was 8.3 (range, 0-19.7). Patients with SUVmax < 6 survived significantly longer than patients with SUVmax ≥ 6 (median 405 days vs 203 days, p = 0.0400). On Kaplan-Meier analysis, SUVmax (p = 0.0400), stage (p = 0.0001), CA19-9 (p = 0.013), CEA (p = 0.006), LN metastasis (p = 0.0001), distant metastasis (p = 0.0020), type of treatment (p = 0.0001) were significantly associated with overall survival. Multivariate analysis study revealed that the patients with lower SUVmax measured from initial staging PET/CT (p = 0.0380), no LN metastasis (p = 0.0260), a lower stage (p = 0.026) and curative treatment (p = 0.0005) had longer survivals. CONCLUSIONS: The present study shows that SUVmax on F-18 FDG PET/CT can provide prognostic information in patients with gallbladder cancer.

High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma.

BACKGROUND: Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. METHODS: Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy). RESULTS: LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. CONCLUSIONS: This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

Hepatic resection for hepatic metastases from gastric adenocarcinoma.

PURPOSE: The effects of hepatic resection on patients with metastatic tumors from gastric adenocarcinomas are unclear. Therefore, we analyzed early clinical outcomes in patients who underwent surgical resection for hepatic metastases from gastric adenocarcinomas. MATERIALS AND METHODS: From January 2003 to December 2010, 1,508 patients with primary gastric cancers underwent curative gastric resections at the Korea Cancer Center Hospital. Of these patients, 12 with liver-only metastases underwent curative hepatic resection. Their clinical data were analyzed retrospectively. RESULTS: The median follow-up period was 12.5 months (range, 1~85 months); no operative mortalities or major complications were observed. Three patients underwent synchronous resections, and 9 underwent metachronous resections. In the latter group, the median interval between gastrectomy and hepatectomy for hepatic metastasis was 10.5 months (range, 5~47 months). The overall 1- and 5-year survival rates of these 12 patients were 65% and 39%, respectively, with a median overall survival of 31.0 months; 2 patients survived for >5 years. CONCLUSIONS: Hepatic resection can be a feasible procedure for treating hepatic metastases from gastric adenocarcinomas. Although this study was small and involved only selected cases, the outcomes of the hepatic resections were comparable and long-term (>5 years) survivors were identified. Surgical resection of the liver can be considered a feasible option in managing hepatic metastases from gastric adenocarcinomas.

Laparoscopic major liver resection in Korea: a multicenter study.

INTRODUCTION: We report our experience with laparoscopic major liver resection in Korea based on a multicenter retrospective study. MATERIALS AND METHODS: Data from 1,009 laparoscopic liver resections conducted from 2001 to 2011 were retrospectively collected. Twelve tertiary medical centers with specialized hepatic surgeons participated in this study. RESULTS: Among 1,009 laparoscopic liver resections, major liver resections were performed in 265 patients as treatment for hepatocellular carcinoma, metastatic tumor, intrahepatic duct stone, and other conditions. The most frequently performed procedure was left hemihepatectomy (165 patients), followed by right hemihepatectomy (53 patients). Pure laparoscopic procedure was performed in 190 patients including 19 robotic liver resections. Hand-assisted laparoscopic liver resection was performed in three patients and laparoscopy-assisted liver resection in 55 patients. Open conversion was performed in 17 patients (6.4 %). Mean operative time and estimated blood loss in laparoscopic major liver resection was 399.3 ± 169.8 min and 836.0 ± 1223.7 ml, respectively. Intraoperative transfusion was required in 65 patients (24.5 %). Mean postoperative length of stay was 12.3 ± 7.9 days. Postoperative complications were detected in 53 patients (20.0 %), and in-hospital mortality occurred in two patients (0.75 %). Mean number and mean maximal size of resected tumors was 1.22 ± 1.54 and 40.0 ± 27.8 mm, respectively. R0 resection was achieved in 120 patients with hepatic tumor, but R1 resection was performed in eight patients. Mean distance of safe resection margin was 14.6 ± 15.8 mm. CONCLUSIONS: Laparoscopic major liver resection has become a reliable option for treatment of liver disease in Korea.

Extrahepatic recurrence of hepatocellular carcinoma after curative hepatic resection.

BACKGROUNDS/AIMS: This study was designed to compare the recurrence patterns after curative hepatectomy, to compare the prognosis according to the initial site of metastasis, and to investigate the independent predictive factors associated with extrahepatic recurrence in hepatocellular carcinoma (HCC) patients after curative hepatectomy. METHODS: From January 2000 to July 2009, 307 patients underwent curative hepatectomies for HCC at our institution; 152 patients showed recurrences. Patients were divided into 2 groups according to their initial recurrence site: the intrahepatic recurrence (IHR) group and extrahepatic recurrence (EHR) group. The IHR group was comprised of 111 patients and the EHR group was comprised of 41 patients. The study investigated the preoperative, intraoperative, and postoperative factors related to the recurrence pattern retrospectively and compared the prognoses of the patients. RESULTS: A five-year survival rate after an initial recurrence was lower in the EHR group (21.5%) than the IHR group (36.3%) (p<0.001). The preoperative alpha-fetoprotein (AFP) level was an independent risk factor for extrahepatic recurrence (p=0.014). CONCLUSIONS: Patients with a preoperative AFP level greater than 200 ng/ml have a higher incidence of extrahepatic metastases after a curative resection of HCC. Increased level of preoperative AFP is an indication for a short-term follow up hepatectomy.

Fat Tissue Infiltration into the Pancreas Parenchyme and Its Effect on the Result of Surgery.

PURPOSE: In Korea, there are few reports regarding the infiltration of fat tissue in pancreatic parenchyma in surgically resected organs. It is necessary to ascertain the correlation between the presence of fat tissue in the resection margin of the pancreas and the surgery outcome. METHODS: Fifty four patients who underwent pancreatic resection from Jan. 2007 to Nov. 2008 were enrolled in this study. Pathologic examination was performed to determine the presence of fat tissue in resected pancreatic parenchyma. Statistical correlation between the presence of fat tissue with clinical parameters and postoperative complication rates was analyzed. RESULTS: Among the specimens of all fifty four patients, fat tissue was found in 32 specimens of patients (59.3%). Female gender and patients whose body mass index exceeded 24 kg/m(2) were statistically correlated with the presence of the fat tissue in pancreatic parenchyma. There was no statistical relationship between infiltration of fat tissue with postoperative complications. CONCLUSION: This study may serve as the base data for study in radiological imaging in detecting pancreatic tissue. A further larger scaled study is needed to validate the result of this study.

Hypophosphatemia after live donor right hepatectomy.

BACKGROUND: It is known that hypophosphatemia can frequently develop after hepatectomy and may result from an increased renal phosphate leak. However, its clinical significance has not been well defined in live donor right hepatectomy (LDRH). The purpose of this study was to investigate the correlation between postoperative hypophosphatemia and both donor morbidity and the degree of hepatic resection in LDRH. METHODS: In all, 88 live liver donors were enrolled, who had undergone right hemihepatectomy between January 2002 and December 2005. Based on the severity of the postoperative hypophosphatemia, we divided the donors into 3 groups: mild (1.5-2.5 mg/dL, n = 30), moderate (1.0-1.5 mg/dL, n = 41), and severe (<1.0 mg/dL, n = 17), and we compared the incidence of complications among these groups. In addition, we investigated the possible correlation between the nadir phosphorus levels and both remnant liver volume and alkaline phosphate (ALP) levels. RESULTS: All donors developed hypophosphatemia postoperatively. The mean value of the nadir phosphorus levels was 1.4 +/- 0.04 mg/dL. However, no significant difference was observed in the incidence of postoperative complications among the hypophosphatemia groups. The phosphorus level was positively correlated with the remnant liver volume (r = 0.389, P < 0.001), but it was negatively correlated with a postoperative increase in the ALP (r = -0.276, P = 0.014). CONCLUSIONS: Hypophosphatemia developed very frequently after LDRH. However, transient hypophosphatemia was unlikely to lead to severe complications in healthy donors. Therefore, based on the serum level, oral or intravenous phosphorus replacement treatment might be more appropriate than routine aggressive replacement by TPN. In addition, although the factors responsible for posthepatectomy hypophosphatemia have not been identified, they might be substances that are associated with hepatic regeneration.