Double tract reconstruction versus double flap technique: short-term clinical outcomes after laparoscopic proximal gastrectomy for early gastric cancer.

BACKGROUND: Laparoscopic proximal gastrectomy (LPG) is increasingly preferred for operative management of early gastric cancer, although there is no consensus on a standard reconstruction method after resection. Two popular methods used after LPG are double tract reconstruction (DTR) and double flap technique (DFT). This study assessed comprehensive clinical outcomes including quality of life (QoL) and body composition change 1 year after DFT and DTR. METHODS: We retrospectively reviewed prospectively collected data from 51 to 18 patients who underwent DTR and DFT, respectively, between September 2014 and December 2018. Short-term surgical outcomes, presence of reflux esophagitis, nutritional supplementation, medications, nutritional status (laboratory results and body composition analysis), and QoL measured preoperatively and at 1 year postoperatively were compared between both groups. RESULTS: Both groups did not differ significantly in clinicopathological characteristics. The DFT as compared to the DTR group required significantly longer time for anastomosis (79.4 vs. 60.9 min, p < 0.001) and use of fewer staplers (3.39 vs. 6.86, p < 0.001). While the presence of endoscopic reflux esophagitis and iron/vitamin B12 replacement were comparable, the DTR group showed a higher tendency of taking anti-reflux medications for reflux symptoms (DTR: 13.7% vs. DFT: 0.0%, p = 0.177). The DTR group lost significantly more weight (p = 0.038) and body fat (p = 0.009). QoL analysis showed significant deterioration in diarrhea, eating restriction, and taste problems in both groups (DTR group: p = 0.008, p < 0.001, p = 0.010, respectively, and DFT group: p = 0.017, p = 0.024, p = 0.034, respectively). However, only the DTR group showed significant deterioration in physical function (p = 0.009), role function (p = 0.033), nausea/vomiting (p = 0.041), appetite loss (p = 0.019), dysphagia (p = 0.001), pain (p = 0.025), and body image (p = 0.004). CONCLUSIONS: Despite requiring a longer anastomosis time, performing DFT after LPG was shown to be an ideal reconstruction method in terms of better 1-year QoL and nutritional outcome. Further larger studies over longer postoperative periods are necessary to confirm our findings.

ERK1 Directly Interacts With JNK1 Leading to Regulation of JNK1/c-Jun Activity and Cell Transformation.

ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phosphorylation cascades; however, the activation of these pathways is not mutually exclusive. Little doubt exists that MAP kinases engage in crosstalk, but the extent or the direct effect of these "conversations" is unclear. Here, we report the possible points of direct interaction as "crosstalk" points between ERK1 and JNK1 and a potential mechanism for ERK1 function in repressing Ras/JNK-mediated cell transformation. ERK1, but not ERK2, directly interacts with and antagonizes JNK1 phosphorylation and activity, resulting in suppression of neoplastic cell transformation mediated by the Ras/JNK/c-Jun signaling pathway. Interestingly, ERK1 phosphorylation was increased in normal tissues compared to liver cancer tissues. Furthermore, predominant JNK/c-Jun activation was observed in liver cancer tissues. These phenomena can provide evidence for the existence of a functional association between ERK and JNK signaling pathways during in vivo tumorigenesis. Overall, our findings provide new evidence supporting the paradigm of an ERK1/JNK1 antagonistic interaction as a novel mechanism of trans-regulation between different MAP kinase signaling modules. J. Cell. Biochem. 118: 2357-2370, 2017. © 2017 Wiley Periodicals, Inc.

Hepatic ischemia/reperfusion injury disrupts the homeostasis of kidney primary cilia via oxidative stress.

Acute kidney injury (AKI) is a major complication of hepatic surgeries. The primary cilium protrudes to the lumen of kidney tubules and plays an important role in renal functions. Disruption of primary cilia homeostasis is highly associated with human diseases including AKI. Here, we investigated whether transient hepatic ischemia induces length change and deciliation of kidney primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress regulates those. HIR induced damages to the liver and kidney with increases in ROS/oxidative stress. HIR shortened the cilia of kidney epithelial cells and caused them to shed into the urine. This shortening and shedding of cilia was prevented by Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, an antioxidant). The urine of patient undergone liver resection contained ciliary proteins. These findings indicate that HIR induces shortening and deciliation of kidney primary cilia into the urine via ROS/oxidative stress, suggesting that primary cilia is associated with HIR-induced AKI and that the presence of ciliary proteins in the urine could be a potential indication of kidney injury.

One Hundred Hepatectomies without Hospital Death under Intermittent Hepatic Inflow Clamping for 30 Minute Duration.

BACKGROUND/AIMS: Temporary clamping of the hepatic inflow is routinely applied to minimize haemorrhage during liver parenchyma. In this report, we describe successful intermittent application of the hepatic inflow for 30 minutes with zero hospital death in consecutive 100 hepatectomies. METHODOLOGY: One hundred consecutive patients undergoing elective liver resection were entered for this prospective study. A synthetic protease inhibitor (gabaxate mesilate, GM) was intravenously administrated continuously starting 12 hours before the operation until the second postoperative day. The patients underwent hepatectomy with a cycle consisting of intermittent application of inflow clamping for 30 minutes, followed by 5 minutes of declamping. Intraoprative data were evaluated together with complications and hospital death rates. Liver function tests were performed on postoperative days, 1, 3 and 7. RESULTS: All the patients discharged the hospital with a zero motality and an average hospital stay of 8 days postoperatively. Peak for aminotransferase were observed postoperative day 1 (382 ± 268, 245 ± 204 IU/L, mean ± SD for serum S-AST and S-ALT). The bilirubin and prothrombin times were normalized day 7 postsurgery. There were no differences between GM protocols. CONCLUSIONS: We have successfully confirmed that a cycle consisting of intermittent application of the hepatic inflow clamping yields safe hepatectomy under effective control of bleeding, when combined with use of a protease inhibitor.

Various types of reconstruction after pancreaticoduodenectomy for the patients who underwent all types of gastrectomy: a single-enter experience.

Purpose: The incidence of patients requiring pancreaticoduodenectomy (PD) following any type of gastrectomy is increasing as the population of elderly patients is increasing, especially in endemic areas of gastric cancer such as Korea. All types of gastrectomy can be categorized as subtotal gastrectomy with Billroth I (BI), Billroth II (BII), and total gastrectomy with Roux-en-Y anastomosis. In this paper, we reviewed our experiences of PD for patients who previously underwent gastrectomy. Methods: We reviewed the medical records of the patients who underwent PD following any type of gastrectomy among 505 consecutive patients who underwent PD in a single institution between 2011 and 2020 retrospectively. Results: There were 13 patients who had undergone gastrectomy including 7 patients of BI, 1 patient of BII, and 5 patients of total gastrectomy. For all 7 patients of BI, the reconstruction was not different from conventional PD. For the 1 patient of BII, previous gastrojejunal anastomosis was preserved and reconstruction was performed in Roux-en-Y method. For the 5 patients with total gastrectomy, 2 different types of reconstruction were performed. In one patient, we removed the remaining jejunum with the specimen, and reconstruction was performed. For the other 4 patients, the remaining jejunum, distal to the Treitz ligament, was preserved and was utilized for anastomosis. Surgeries for all patients were uneventful. Conclusion: PD following any type of gastrectomy can be safe. Especially, if the length of remained jejunum is long enough, its utilization for the reconstruction can be an appropriate option.

Unfavorable effect of high postoperative fluid balance on outcome of pancreaticoduodenectomy.

Purpose: Despite the many efforts to overcome postoperative complications, pancreaticoduodenectomy (PD) is still accompanied with considerable concerns of lethal complications. The clinical factors are known to affect postoperative outcomes such as diameter of pancreatic duct, texture of pancreas, and comorbidity of the patients are mostly uncorrectable. Thus, investigation for correctable risk factors is required. Recently, perioperative fluid volume was reported to be associated with complications after PD. This study aims to determine the relationship between postoperative fluid balance and surgical outcome after open PD. Methods: We reviewed, retrospectively, 172 consecutive patients who underwent open PD in a single institution between 2015 and 2019. The status of perioperative fluid balance 2 days after surgery and clinical factors were investigated to determine the association with postoperative outcome including postoperative pancreatic fistula (POPF). According to postoperative fluid balance, patients were divided into high- and low-balance groups, and clinical features and surgical outcomes were compared between both groups. Multivariate analysis were performed to identify risk factors for POPF. Results: The percentage of morbidity and the incidence of POPF were higher in the high-balance group compared to the low-balance group (61.6% vs. 37.2%, P = 0.001; 15.1% vs. 3.5%, P = 0.009). High postoperative fluid balance and the presence cardiovascular disease were correlated with POPF on multivariate analysis (odds ratio [OR], 4.574; 95% confidence interval [CI], 1.229-17.029; P = 0.023 and OR, 3.517; 95% CI, 1.209-12.017; P = 0.045). Conclusion: Higher amount of postoperative fluid balance and the presence of cardiovascular disease are associated with POPF after PD.

Factors associated with prolonged viral detection in asymptomatic and mildly symptomatic patients with SARS-CoV-2 infection.

INTRODUCTION: Data on the clinical course and duration of viral RNA detection in patients with mild or asymptomatic coronavirus disease 2019 are limited. METHODOLOGY: In this retrospective analysis, clinical characteristics and serial real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results were reviewed in a cohort of 1186 asymptomatic and mildly symptomatic coronavirus disease 2019 patients in South Korea. Factors associated with prolonged duration of RT-PCR positivity for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) were also evaluated. Patients with two consecutive negative RT-PCR tests ≥ 24 hours apart were considered to be in virologic remission and discharged. RESULTS: The average virologic remission period, defined as the number of days from diagnosis to virologic remission, was 22.0 ± 9.7 days; patients with longer than 30 days accounted for 21.2% (251/1186) of the population. Patients who took longer than 30 days to achieve virologic remission had a higher frequency of overall symptoms (p < 0.001) and respiratory symptoms (p < 0.001). In multivariate analysis using Cox-proportional hazard regression, it was confirmed that respiratory symptoms (hazard ratio [HR], 0.7372; 95% confidence interval [CI], 0.6540-0.8311) and gastrointestinal symptoms (HR, 0.8213; 95% CI, 0.6970-0.9679) were independent factors associated with prolonged virologic remission. Age and co-morbidity such as diabetes and hypertension were not associated with the prolonged RT-PCR positivity. CONCLUSIONS: A considerable percentage of asymptomatic and mildly symptomatic patients with coronavirus disease 2019 showed prolonged RT-PCR positivity for SARS-CoV-2; which was independently associated with the presence of symptoms, but not with age and co-morbidity.

Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.

The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT.

Prognostic factors after early recurrence in patients who underwent curative resection for hepatocellular carcinoma.

BACKGROUND: The prognosis of the patients with early recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) is usually dismal. METHODS: One hundred twenty-four patients underwent curative resection for HCC at Kyungpook National University Hospital from January 2002 to December 2006. An early recurrence was defined as a recurrence within 2 years after a curative resection. The risk factors associated with an early recurrence were analyzed as well as other risk factors correlated with survival after early recurrence. RESULTS: Early disease recurrence developed in 56 patients (45.2%). The risk factors associated with an early recurrence were a tumor size larger than 5 cm (P = 0.001) and the presence of tumor micrometastasis (P < 0.001). The 1 year/2 year overall survival, after early recurrence, was 57.0%/41.0% and the preoperative α-fetoprotein, C-reactive protein (CRP), tumor size, macroscopic vascular invasion, and number of tumors were associated with survival on the univariate analysis. The multivariate analysis showed that the independent risk factors for survival, after early disease recurrence, were a preoperative CRP >1.0 mg/dl and macroscopic vascular invasion. (P = 0.004, P < 0.001, respectively). CONCLUSION: The preoperative CRP and macroscopic vascular invasion were associated with the aggressiveness of early recurrent HCC.

Prolonged SARS-CoV-2 detection and reversed RT-PCR results in mild or asymptomatic patients.

BACKGROUND: The clinical course and viral detection period in mild or asymptomatic coronavirus disease 2019 (COVID-19) patients are not yet known. The presumed low diagnostic sensitivity of upper respiratory specimens for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) makes it difficult to confirm infection and recommend de-isolation. METHODS: We retrospectively reviewed real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test results of mild or asymptomatic COVID-19 patients who were admitted at the Daegu-Gyeongbuk 7th community treatment centre in Korea between 9 March 2020 and 10 April 2020. Patients underwent an upper respiratory RT-PCR test every week until discharge. From the RT-PCR results, we evaluated the rate of prolonged (>3 weeks) SARS-CoV-2 RNA positivity. We analysed the proportion of reversed results, defined as a positive or indeterminate result one day after a negative RT-PCR result, according to time (<14, 15-21, 22-28, >28 days) from the initial positive RT-PCR result. RESULTS: In 23% (69/300) of patients, SARS-CoV-2 was detected more than 3 weeks after the initial positive RT-PCR. In 14% (42/300) of patients, the RT-PCR results were positive for more than 4 weeks. For 37.5% (152/405) of negative RT-PCR results, the results were reversed in the next day's test. And 43.5% (123/283) of negative RT-PCR results were reversed within 3 weeks of diagnosis. CONCLUSIONS: The detection of SARS-CoV-2 lasting more than 3 weeks was common in mild or asymptomatic patients. Upper respiratory RT-PCR results were frequently reversed from negative to positive.

Malignant melanoma of the gallbladder: A case report and literature review.

Metastatic melanoma of the gallbladder is extremely rare. It has a poor prognosis. Its optimal treatment remains unclear. Surgical resection is generally considered the mainstay of treatment. However, there are no standards to guide the choice between open surgery and laparoscopic surgery. Criteria for the extent of surgical dissection have not been established yet either. We report a patient diagnosed with gallbladder cancer who underwent extended cholecystectomy but had metastatic melanoma at the final biopsy. We reviewed the literature on the treatment of metastatic melanoma in the gallbladder and compared it with our case to determine a treatment strategy.

Optimal surgical treatment in patients with T1b gallbladder cancer: An international multicenter study.

BACKGROUND: There is no consensus on the optimal treatment of T1b gallbladder cancer (GBC) due to the lack of evidence and the difficulty of anatomy and pathological standardization. METHODS: A total of 272 patients with T1b GBC who underwent surgical resection at 14 centers with specialized hepatobiliary-pancreatic surgeons and pathologists in Korea, Japan, Chile, and the United States were studied. Clinical outcomes including disease-specific survival (DSS) rates according to the types of surgery were analyzed. RESULTS: After excluding patients, the 237 qualifying patients consisted of 90 men and 147 women. Simple cholecystectomy (SC) was performed in 116 patients (48.9%) and extended cholecystectomy (EC) in 121 patients (51.1%). The overall 5-year DSS was 94.6%, and it was similar between SC and EC patients (93.7% vs. 95.5%, P = 0.496). The 5-year DSS was similar between SC and EC patients in America (82.3% vs. 100.0%, P = 0.249) as well as in Asia (98.6% vs. 95.2%, P = 0.690). The 5-year DSS also did not differ according to lymph node metastasis (P = 0.688) or tumor location (P = 0.474). CONCLUSIONS: SC showed similar clinical outcomes (including recurrence) and survival outcomes as EC; therefore, EC is not needed for the treatment of T1b GBC.

Practical experience of a no abdominal drainage policy in patients undergoing liver resection.

BACKGROUND/AIMS: Routine use of abdominal drainage after liver resection is controversial. The aim of this study was to investigate the practical application of a "no abdominal drainage" policy for consecutive patients undergoing hepatic resection. METHODOLOGY: The present trial included 60 consecutive patients who underwent elective hepatic resection. Fifty-two patients underwent no abdominal drainage, and in the remaining eight drainage was necessary because of gross contamination of the surgical field associated with bilioenteric anastomosis, uncontrollable bile leakage from the cut surface of the liver, or the surgeon's preference. Patient demographics, intraoperative data, and postoperative complications and mortality were evaluated. RESULTS: There was no hospital death. Eight complications occurred in 8 patients in the no-drainage group (morbidity rate 15.4%, 8/52): bleeding, abscess, ascites requiring peritoneal tap, pleural effusion requiring thoracentesis, and pneumonia in one case each, and three cases of wound infection. Three complications were encountered in 2 patients in the drainage group (morbidity rate 25%, 2/8): bleeding, infected biloma and pleural effusion in one case each. Postoperative hospital stay tended to be shorter in the no-drainage group (10.7 +/- 3.9 days) than in the drainage group (15.6 +/- 6.4 days) (p = 0.07). Considering early uneventful removal of the drain on the morning of postoperative day 1, half of the drained patients might have not required drainage. Furthermore, in the setting of concomitant bilioenteric anastomosis (n=4), one patient underwent hepatectomy uneventfully without drainage, and two of three patients with drainage had their drains removed successfully on day 1. The third patient retained the drain for an unnecessarily long period, but did not develop subsequent complications. CONCLUSIONS: Our data support the view that prophylactic abdominal drainage is unnecessary in most patients who undergo elective hepatic resection. Bilioenteric anastomosis may not be a contraindication for a no abdominal drainage policy.

Intrahepatic splenic tissue without medical history of splenic injury or splenectomy.

Only a few cases of intrahepatic splenic tissue have so far been reported in the English literature. Those cases were developed after splenic injury or a splenectomy. We report here a case of intrahepatic splenic tissue which has two distinctive features compared to previous literature. A 59-year-old female who previously had no medical history of splenic injury or splenectomy underwent hepatic resection for intrahepatic tumor mimicking hepatocellular carcinoma. However, pathologic examination revealed it as intrahepatic splenic tissue directly abutted to the normal liver tissue without a capsule. Lacking an invasive diagnostic modality, the diagnosis of intrahepatic splenic tissue without an accompanying medical history is very difficult.

Successful intermittent application of the Pringle maneuver for 30 minutes during human hepatectomy: a clinical randomized study with use of a protease inhibitor.

BACKGROUND/AIMS: There is experimental evidence that the liver can safely tolerate a cycle involving application of the Pringle maneuver for 30 minutes each time. METHODOLOGY: One hundred and twenty patients who underwent elective hepatectomy were randomly assigned to two groups of intermittent occlusion (30-min or 15-min Pringle group, n=60 each). A synthetic protease inhibitor (gabexate mesilate, GM, 2 mg/kg/h) was administered to pharmacologically alleviate visceral congestion, accompanied by hepatic pedicle clamping. Intraoperative data, liver function parameters and portal plasma levels of the inflammatory cytokine, interleukin (IL)-6 (a marker reflecting the status of visceral congestion), were examined as well as the postoperative course. Additionally, ten more patients randomly underwent right hepatectomy without GM, in order to clarify the influence of this agent on the present outcomes. RESULTS: The two groups of patients were comparable in terms of preoperative assessments, hepatic inflow occlusion time, extent of resection and background liver conditions. The 30-min Pringle group showed less blood loss during surgery (p=0.02) with a tendency for better postoperative mortality and morbidity. The postoperative liver functions were similar between the two groups. The portal plasma levels of IL-6 during pedicle clamping did not differ significantly between the two groups. When GM was not used, the 30-min intermittent Pringle maneuver induced a two-fold rise in serum transaminase levels on day 1 compared with the 15-min group. CONCLUSIONS: Our study indicates that intermittent application of the Pringle maneuver for 30 minutes each time can be accomplished effectively and safely for human hepatectomy, when combined with use of a protease inhibitor.

Evaluation of a protease inhibitor in the prevention of ischemia and reperfusion injury in hepatectomy under intermittent Pringle maneuver.

BACKGROUND: The severity of ischemia and reperfusion (I/R) injury is an important determinant of patient outcome in hepatic surgery. The aim of this study was to investigate the efficacy of a protease inhibitor in alleviating I/R injury to human liver in the setting of hepatectomy under intermittent Pringle maneuver. METHODS: Sixty patients who underwent liver resection under conditions of intermittent inflow occlusion were randomly assigned to 2 groups (n = 30 each) according to the use of a synthetic protease inhibitor (gabexate mesilate or GM). GM was administered intravenously at a dosage of 2.0 mg/kg/h starting 12 hours before surgery until postoperative day 2. Preoperative and intraoperative clinical variables and postoperative outcomes were evaluated. The plasma levels of a cytokine, interleukin (IL)-6, as well as laboratory biochemical liver function parameters were analyzed to evaluate hepatic I/R injury. RESULTS: The 2 groups of patients were comparable with regard to hepatic inflow occlusion time, extent of liver resection, and background liver histology. The preoperative administration of GM (GM group) substantially alleviated hepatic I/R injury compared with the untreated control group; postoperative serum transaminase levels were significantly decreased in association with marked suppression of IL-6 levels in blood circulation during surgery. This was accompanied by a lower incidence of postoperative complications. The patients without postoperative complications had significantly lower activities of plasma IL-6 at 24 hours after surgery. CONCLUSIONS: This prospective randomized study demonstrated the hepatoprotective effect of a synthetic protease inhibitor in the setting of hepatectomy under the intermittent Pringle maneuver.

Outcomes and recurrence pattern after non-anatomic liver resection for solitary hepatocellular carcinomas.

BACKGROUNDS/AIMS: Anatomic resection (AR) is preferred for eradicating portal tributaries in patients with hepatocellular carcinoma (HCC). However, the extent of resection is influenced by underlying liver disease and tumor location. We compared the surgical outcomes and recurrence pattern between non-anatomic resection (NR) and AR. METHODS: From March 2009 to February 2012, 184 patients underwent surgical resection for HCC. Among these, 79 patients who were primarily treated for a single tumor without rupture or macroscopic vascular invasion were enrolled. The patients were divided into 2 groups based on the extent of resection: AR (n=31) or NR (n=48). We compared the clinical characteristics, overall survival, disease-free survival, pattern of recurrence, and biochemical liver functions during the perioperative period between the two groups. RESULTS: The extent of resection had no significant effect on overall or disease-free survival rates. The overall 1- and 3-year survival rates were 97% and 82% in the AR group, and 96% and 89% in the NR group, respectively (p=0.49). In addition, the respective 1- and 3-year disease-free survival rates for the AR and NR groups were 84% and 63%, and 85% and 65%, respectively (p=0.94). On the other hand, the presence of hepatic cirrhosis and a tumor size of >5 cm were significant risk factors for recurrence according to multivariate analysis (p<0.001 and p=0.003, respectively). The frequency of early recurrence, the first site of recurrence, and the pattern of intrahepatic recurrence were similar between the 2 groups (p=0.419, p=0.210, and p=0.734, respectively); in addition, the frequency of marginal recurrence did not differ between the 2 groups (1 patient in the AR group and 2 in the NR group). The NR group showed better postoperative liver function than the AR group. CONCLUSIONS: Non-anatomic liver resection can be a safe and efficient treatment for patients with a solitary HCC without rupture or gross vascular invasion.

[The comparative results of radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma].

BACKGROUND/AIMS: Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC. METHODS: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups. RESULTS: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups. CONCLUSIONS: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results.

Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray.

We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.

Hepatocyte protection by a protease inhibitor against ischemia/reperfusion injury of human liver.

BACKGROUND: Total clamping of the hepatic pedicle can induce profound hepatic ischemia/reperfusion (I/R) injury, which remains a potentially lethal problem after hepatectomy. STUDY DESIGN: The purpose of this study was to evaluate the efficacy of a protease inhibitor in ameliorating I/R injury of the human liver. In a prospective, randomized, clinical study, 66 patients who underwent liver resection under conditions of continuous inflow occlusion were randomly assigned to three groups: 25 patients were given a synthetic protease inhibitor (gabexate mesilate [GM], 2.0 mg/kg/hr) intravenously starting 24 hours before surgery until postoperative day 3 (preop GM group); 16 were similarly given GM at the beginning of surgery (intraop GM group); and 25 served as controls (without GM group). Laboratory data and intraoperative and postoperative variables were analyzed and plasma levels of cytokines--tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6)--were measured to determine the relationship between surgical stress and hepatic I/R injury. RESULTS: The three groups of patients were similar in terms of age, gender, preoperative assessments, hepatic inflow occlusion time (approximately 50 minutes), extent of resection (proportion of major and minor hepatectomy), and background liver conditions. Preoperative administration of gabexate mesilate (preop GM group) substantially ameliorated hepatic I/R injury as compared with the other patients (intraop and without GM groups); postoperative serum transaminase levels were notably decreased in association with marked suppression of IL-6 levels in blood circulation during liver surgery. This was accompanied by a lower rate of postoperative complications and no mortality. Gabexate mesilate pretreatment abrogated the positive correlation between postreperfusion hepatocyte injury and hepatic ischemia time. CONCLUSIONS: Preoperative administration of GM is useful for preventing I/R injury of the human liver, accompanied by suppression of the plasma proinflammatory cytokine IL-6.