Yoon Jin Hwang

In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD)

The detoxification capacities of single‐pass albumin dialysis (SPAD), the molecular adsorbents recirculation system, (MARS) and continuous veno‐venous hemodiafiltration (CVVHDF) were compared in vitro. In each experiment 4,100 mL of toxin‐loaded human plasma was processed for 6.5 hours. MARS treatment (n = 6) was undertaken in combination with CVVHDF. For SPAD (n = 6) and CVVHDF (n = 6) a high‐flux hollow fiber hemodiafilter (identical to the MARS filter) was used. Levels of ammonia, urea, creatinine, bilirubin, and bile acids were determined. Concentrations before and after application of detoxification procedures were expressed as differences and were compared using the Kruskal‐Wallis test. Post hoc comparisons for pairs of groups were adjusted according to Bonferroni‐Holm. Time, group, and interaction effects were tested using the nonparametric ANOVA model for repeated measurements. SPAD and CVVHDF induced a significantly greater reduction of ammonia levels than MARS. No significant differences were found among SPAD, MARS, and CVVHDF with respect to other water‐soluble substances. SPAD induced a significantly greater reduction in bilirubin levels than MARS. Reductions in bile acid levels were similar for SPAD and MARS. When operating MARS in continuous veno‐venous hemodialysis mode, as recommended by the manufacturer, no significant differences in the removal of bilirubin, bile acids, urea, and creatinine were found. However, MARS in continuous veno‐venous hemodialysis mode was significantly less efficient in removing ammonia than MARS in CVVHDF mode. In conclusion, the detoxification capacity of SPAD is similar to or even greater than that of MARS. (HEPATOLOGY 2004;39:1408–1414.)

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

The prognosis of the patients with early recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) is usually dismal.

Prognostic factors in patients with middle and distal bile duct cancers

AIM To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers. METHODS Between August 1990 and June 2011, data regarding the clinicopathological factors of 194 patients with surgical and pathological confirmation were collected. A total of 133 patients underwent resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct resection (BDR) was selected according to the sites of tumors and co-morbidities of the patients after confirming resection margin by the frozen histology in all cases. Univariate and multivariate analyses of clinicopathologic factors were performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis. RESULTS The overall 5-year survival rate for the 133 patients who underwent resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3 years among the 61 patient who underwent nonresectional surgeries. The 5-year survival rate of the patients who underwent a PD (n = 90) was higher than the rate of those who underwent BDR (n = 43), although the difference was not statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762). The 5-year survival rates of R0 and R1 resections were not significantly different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P = 0.0001). Although positive lymph node, presence of perineural invasion, presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis (TNM) stage, and involvement of resection margin were significant prognostic factors in univariate analysis, multivariate analysis identified only TNM stage and LVI as independent prognostic factors. CONCLUSION PD had a greater likelihood of curative resection and R1 resection might have some positive impact. The TNM stage and LVI were independent prognostic factors.

Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site

Extrahepatic bile duct (EHBD) cancer may occur metachronously, and these cancers are resectable with a favorable prognosis. We aimed to identify the pattern of metachronous EHBD cancer. We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer. A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor (pT1N0M0). A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer (pT2N1M0). Imaging studies of both patients taken at 14 and 24 mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy (PD). Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas (pT3N0M0). Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery. Through a review of the literature on these cases, we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia. The proximal remnant bile duct was most commonly involved. Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor. Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors.

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.

Totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy using anterior approach in HCC patient with Type II portal vein anomaly

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gradually developed because of rapid hypertrophy of the future liver remnant volume (FLR) in spite of high morbidity. To minimize the patients postoperative pain and morbidity including wound complication caused by two consecutive major abdominal operations, we adopted a totally laparoscopic approach and used a composite mesh graft. Also, to maximize the oncologic efficacy, we adopted the “anterior approach” technique. A 44-year-old woman with large hepatitis B-related hepatocellular carcinoma (HCC) in her right lobe was transferred to our hospital for surgical treatment. Preoperatively predicted FLR by a CT scan was 21% and type II portal vein anomaly was detected. A totally laparoscopic approach was planned. During the first stage operation, right anterior and posterior portal veins were meticulously dissected and tied. After parenchymal transection by the “anterior approach” technique, two glissonian pedicles of the right liver were individually isolated. A composite mesh graft was used to prevent severe adhesion on both liver partition surfaces. During the second-stage operation, 9 days after the first stage operation, the two isolated glissonian pedicles were initially transected. After full mobilization of the right lobe, the right hepatic vein was also transected. The right lobe was removed through the Pfannenstiel incision. She was discharged 7 days after the second stage operation. Her postoperative course was uneventful and there was no HCC recurrence for 15 months after hepatectomy. A totally laparoscopic ALPPS procedure can be a feasible technique that ensures patient safety and oncologic superiority, even in patients with complicated anatomical variation.