Emergency, ABO-Incompatible Living Donor Liver Re-Transplantation for Graft Failure Complicated by Pneumonia-Associated Sepsis.

Although liver re-transplantation is the only therapeutic option for acute and chronic graft failure, few studies have addressed the use of ABO-incompatible living donors in the emergency setting. Here, based on our experience, we report a successful case of emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation (LDLT) for late graft failure from chronic rejection complicated by pneumonia-related sepsis. A fifty-five-year-old man had undergone LDLT for hepatocellular carcinoma accompanied by hepatitis C virus (HCV)-related cirrhosis in 30 September 2013. The voluntary donor was his 56-year-old wife, who was also a carrier of HCV. The donor and recipient blood types were the same: O and Rh positive. She underwent a right hepatectomy and was discharged on postoperative day (POD) seven. The patient was also discharged without complications on POD eleven and was followed up with on an outpatient basis. Abdominal distension and jaundice were developed at 6 months after LDLT, when the serum total bilirubin level was 2.7 mg/dL. The serum total bilirubin levels increased rapidly to 22.9 mg/dL over the next 4 months. Chronic rejection was diagnosed via liver biopsy. On 3 October 2014, he developed pneumonia-related sepsis and showed the progressive deterioration of liver function. Liver re-transplantation using the right liver from his ABO-incompatible, 20-year-old nephew was performed as an emergency in 15 October 2014. The donor blood type was A and Rh positive. The resection of the failed graft and the implantation of a new graft was performed by the intragraft dissection technique to re-use previously transplanted graft vessels in order to cope with severe adhesions. The recipient went through a gradual recovery process and was finally discharged on POD 50 with normal liver function, while the donor had an uneventful recovery and was discharged on POD 7. Biloma due to bile leak was detected three months after re-transplantation and was cured by percutaneous interventional procedures. Since then, the postoperative course has been event-free at regular outpatient follow-ups. The patient has so far had normal laboratory findings and no signs of complications. It has been 98 months since the re-transplantation, and the recipient and two donors are still in good condition with normal liver function, having complete satisfaction with the results obtained from this re-transplantation. In conclusion, long-term, satisfactory outcomes can be achieved in emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation for graft failure complicated by pneumonia-related sepsis in selected patients.

Metachronous pancreatic cancer 18 years after resection of common bile duct cancer: A case report.

We report an extremely rare case of metachronous double cancers of the bile duct and pancreas in a single patient who underwent successful curative resections consecutively. At the age of 57, a woman underwent pylorus-preserving pancreaticoduodenectomy for a lesion that was pathologically diagnosed as moderately differentiated adenocarcinoma of the distal common bile duct. Eighteen years later, a pancreatic mass was detected during a follow-up examination. Abdominal computed tomography showed a bigger 2.3 cm lesion at the remnant pancreas body, which suggested a diagnosis of primary pancreatic cancer or metastasis. After admission and further work-up confirming no other lesions, completion total pancreatectomy was performed. The pathological diagnosis of the resected specimen was moderately differentiated pancreatic ductal adenocarcinoma, and this case highlights the occurrence of metachronous double primary cancers developed in both the distal bile duct and the pancreas with an interval of 18 years. This is the first report on the metachronous primary cancers of the bile duct and pancreas with a long interval within an English review of the literature in the MEDLINE. This case serves as another data point to guide surgeons that they should be vigilant for the postoperative long-term surveillance of patients with pancreatobiliary cancer.

Minimal Surgical Manpower for Living Donor Liver Transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) is widely performed with good outcomes in the current era of improved surgical techniques. However, few studies have addressed how many human resources are required in the surgery itself. This study aimed to introduce how to perform LDLT with minimal manpower and evaluate the outcomes in adult patients. METHODS: The main surgical procedures of donor and recipient operations of LDLT were performed by a single specialist surgeon who led a team of minimal manpower that only included one fellow, one resident, one intern, and three nurses. He also provided postsurgical care and followed up all the patients as a primary care physician. The outcomes were analyzed from the standpoints of the feasibility and acceptability. RESULTS: Between November 2018 and February 2020, a total of 47 patients underwent LDLT. Ten patients had ABO-incompatible donors. The median age of the overall recipients was 57 years old (36-71); 37 patients (78.7%) were male. The MELD score was 10 (6-40), and the main etiologies were hepatic malignancy (38 patients or 80.9%) and liver failure (9 patients or 19.1%). The median age of the overall donors was 34 years old (19-62); 22 patients (46.8%) were male. All the graft types were right liver except for one case of extended right liver with middle hepatic vein. All donors had an uneventful recovery with no complications. There was one intraoperative mortality due to cardiac arrest after reperfusion in one recipient. Hepatic artery thrombosis was developed in 5 (10.6%) recipients. An acute rejection episode occurred in one patient. The median follow-up period for all the patients was 32.9 months (range, 24.7-39.8). Biliary complications were developed in 11 (23.4%) recipients. In total, 7 (15%) patients died, including 1 intraoperative mortality, 5 from cancer recurrence, and 1 from intracranial hemorrhage. The 1-, 2-, and 3-year overall survival rates in the recipient group were 91.5%, 87.2%, and 85.1%, respectively. CONCLUSIONS: LDLT with minimal surgical manpower is feasible under the supervision of a single expert surgeon who has the capacity for all the main surgical procedures in both donor and recipient operations without compromising the outcomes in the present era of advanced surgical management.

Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma.

INTRODUCTION: Serum α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy-pro-thrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. METHODS: From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. RESULTS: Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-ß-catenin signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF-ß and VEGF signaling were activated in ↑AFP&L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort. CONCLUSIONS: Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for TP53 and CTNNB1. These findings may facilitate development of an evidence-based approach to treatment.

A multicenter, prospective, randomized clinical trial of marine mussel-inspired adhesive hemostatic materials, InnoSEAL Plus.

PURPOSE: InnoSEAL Plus is an adhesive, coagulant-free hemostatic material that mimics the adhesion mechanism of marine mussels. This study reports on the safety and efficacy of InnoSEAL Plus for patients with hemorrhage after hepatectomy despite first-line hemostasis treatments. METHODS: This is a multicenter, prospective, single-blinded, randomized clinical trial involving 96 hepatectomy patients. TachoSil was used as a comparator group. Three-minute and 10-minute hemostatic success rates were monitored. Rebleeding rates were also observed. Safety was assessed by recording all novel undesirable symptoms. RESULTS: InnoSEAL Plus showed a 3-minute hemostasis rate of 100%, while TachoSil had a rate of 98.0% (48 of 49 patients), demonstrating that the 2 had similar hemostatic efficacies. The difference in efficacy between the test and comparator group was 2.04%, and the lower limit of the one-sided 97.5% confidence interval was -1.92%; as this is greater than the noninferiority limit of -23.9%, the 2 treatments were equivalent. Meanwhile, the 10-minute hemostatic success rate was the same in both groups (100%). No rebleeding occurred in either group. In the safety evaluation, 89 patients experienced adverse events (45 in the test group and 44 in the comparator group). The difference between the 2 groups was not significant. No death occurred after application of the test or comparator group product. CONCLUSION: Given that InnoSEAL Plus is a coagulation factor-free product, the hemostasis results are encouraging, especially considering that TachoSil contains a coagulation factor. InnoSEAL Plus was found to be a safe and effective hemostatic material for control of bleeding in hepatectomy patients.

Hyperammonemic Encephalopathy Mimicking Ornithine Transcarbamylase Deficiency in Fibrolamellar Hepatocellular Carcinoma: Successful Treatment with Continuous Venovenous Hemofiltration and Ammonia Scavengers.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.

Novel Model to Predict HCC Recurrence after Liver Transplantation Obtained Using Deep Learning: A Multicenter Study.

Several models have been developed using conventional regression approaches to extend the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) beyond the Milan criteria. We aimed to develop a novel model to predict tumor recurrence after LT by adopting artificial intelligence (MoRAL-AI). This study included 563 patients who underwent LT for HCC at three large LT centers in Korea. Derivation (n = 349) and validation (n = 214) cohorts were independently established. The primary outcome was time-to-recurrence after LT. A MoRAL-AI was derived from the derivation cohort with a residual block-based deep neural network. The median follow-up duration was 74.7 months (interquartile-range, 18.5-107.4); 204 patients (36.2%) had HCC beyond the Milan criteria. The optimal model consisted of seven layers including two residual blocks. In the validation cohort, the MoRAL-AI showed significantly better discrimination function (c-index = 0.75) than the Milan (c-index = 0.64), MoRAL (c-index = 0.69), University of California San Francisco (c-index = 0.62), up-to-seven (c-index = 0.50), and Kyoto (c-index = 0.50) criteria (all p < 0.001). The largest weighted parameter in the MoRAL-AI was tumor diameter, followed by alpha-fetoprotein, age, and protein induced by vitamin K absence-II. The MoRAL-AI had better predictability of tumor recurrence after LT than conventional models. The MoRAL-AI can also evolve with further data.

Ruptured Massive Hepatocellular Carcinoma Cured by Transarterial Chemoembolization.

Spontaneous tumor rupture is a serious but rare complication of hepatocellular carcinoma (HCC) and has a low survival rate. Here, we report a case of massive HCC that ruptured and was treated successfully with transarterial chemoembolization (TACE). A 55-year-old man with abdominal pain was diagnosed with a 12-cm-wide ruptured HCC at segment 8. The overall liver function was scored as Child-Pugh A, but the single nodule tumor had ruptured; therefore, TACE treatment was initiated. After the first TACE treatment, residual tumors were found; thus, secondary TACE was performed 5 months later. No new lesions or extrahepatic metastases were found 16 months after the first TACE treatment, so hepatic resection was performed for curative treatment. The postoperative pathology results did not reveal any cancer cells; hence, TACE alone resulted in a cure. We report this case because the cure has been maintained for more than 3 years after resection.

Surgery for elderly patients with resectable pancreatic cancer, a comparison with non-surgical treatments: a retrospective study outcomes of resectable pancreatic cancer.

BACKGROUND: We designed a retrospective study to compare prognostic outcomes based on whether or not surgical resection was performed in elderly patients aged(≥75 years) with resectable pancreatic cancer. METHODS: We retrospectively analyzed 49 patients with resectable pancreatic cancer (surgery group, resection was performed for 38 cases; no surgery group, resection was not performed for 11 cases) diagnosed from January 2003 to December 2014 at the National Cancer Center, Korea. RESULTS: There was no significant difference in demographics between the two groups. The surgery group showed significantly better overall survival after diagnosis than the no surgery group (2-year survival rate, 40.7% vs. 0%; log-rank test, p = 0.015). Multivariate analysis revealed that not having undergone surgical resection [hazard ratio (HR) 2.412, P = 0.022] and a high Charlson comorbidity index (HR 5.252, P = 0.014) were independent prognostic factors for poor overall survival in elderly patients with early stage pancreatic cancer. CONCLUSIONS: In the present study, surgical resection resulted in better prognosis than non-surgical resection for elderly patients with resectable pancreatic cancer. Except for patients with a high Charlson comorbidity index, an aggressive surgical approach seems to be beneficial for elderly patients with resectable pancreatic cancer.

Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries. METHODS: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model. RESULTS: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts. CONCLUSIONS: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.

Repeat hepatectomy for recurred colorectal liver metastasis: is it justified?

PURPOSE: Liver resection is considered the only curative treatment modality for colorectal liver metastasis. The recurrence rate after hepatectomy is >50%. Two or more hepatectomies are applied to treat recurred metastases. We assessed the efficiency and feasibility of repeat hepatectomy and analyzed the prognostic factors after a repeat hepatectomy. METHODS: In total, 248 patients were diagnosed with recurred liver metastasis between January 2003 and May 2016. Second and third hepatectomies were performed in 70 and 7 patients, respectively. The other 171 patients did not undergo a repeat hepatectomy. Clinical features were collected from the medical records. We analyzed survival rates of the repeat hepatectomy group and the nonrepeat hepatectomy group. We also investigated factors affecting overall and disease-free survival of patients who received a repeat hepatectomy using univariate and multivariate analyses. RESULTS: Median overall survival was significantly higher in the repeat hepatectomy group than in the nonrepeat group (83.0 months vs. 25.0 months, P < 0.001). The morbidity and mortality rates of repeat hepatectomy were 9.1% and 0%, respectively. Median overall and disease-free survival of the repeat hepatectomy group were 62.0 and 51.0 months, respectively. The number of recurred tumors was the only significant factor for disease-free survival (P = 0.029). None of the factors affected overall survival. CONCLUSION: Repeat hepatectomy is necessary, effective, and safe for treating recurred colorectal liver metastasis. Repeat hepatectomy can be considered in patients with fewer than three recurred metastatic tumors.

Efficacy and safety of prolonged-release versus immediate-release tacrolimus in de novo liver transplant recipients in South Korea: a randomized open-label phase 4 study (MAPLE).

Background: Prolonged-release tacrolimus is associated with better long-term graft and patient survival than the immediate-release formulation in liver transplant patients. However, no clinical data are available to assess the efficacy and safety of early conversion from twice-daily, immediate-release tacrolimus to once-daily, prolonged-release tacrolimus in de novo liver transplant recipients in Korea. Methods: A 24-week, randomized, open-label study was conducted in 36 liver transplant recipients. All patients received immediate- release tacrolimus (0.1-0.2 mg/kg/day, divided into two doses) for 4 weeks after transplantation, at which time 50% of the patients were converted, at a ratio of 1 mg to 1 mg, to prolonged-release tacrolimus (once-daily). The primary efficacy endpoint was the incidence of biopsy-confirmed acute rejection (BCAR) from weeks 4 to 24 after transplantation (per-protocol set). Medication adherence, adverse event profiles, laboratory tests, vital signs, and physical changes were also recorded. Results: BCAR frequency at 24 weeks was similar between the two treatment groups; two cases (mean±standard deviation, 0.14±0.53 cases) of BCAR were reported in one patient treated with prolonged-release tacrolimus (n=14), while no such cases were reported among patients treated with immediate-release tacrolimus (n=12). The tacrolimus blood concentration at weeks 12 and 24, medication adherence, and adverse event profiles were also similar between the formulations, with no unusual laboratory test results, vital signs, or physical changes reported. Conclusions: Early conversion to a simplified, once-daily, prolonged-release tacrolimus regimen may be an effective treatment option for liver transplant recipients in Korea. Larger-scale studies are warranted to confirm non-inferiority to immediate-release tacrolimus formulation in de novo liver transplant recipients.

Perioperative transfusion in pancreatoduodenectomy: The double-edged sword of pancreatic surgeons.

We designed the study to clarify the prognostic significance of perioperative (preoperative, intraoperative, and postoperative) red blood cell (RBC) transfusion following pancreaticoduodenectomy (PD) for periampullary cancers.This study retrospectively analyzed 244 periampullary cancer patients (pancreatic cancer, 124 patients; bile duct cancer, 63 patients; and ampullary cancer, 57 patients) treated by PD from June 2001 to June 2010 at the National Cancer Center, Korea (NCC2017-0106).A total of 112 (46%) of 244 patients had received transfusion (preoperative, 5%; intraoperative, 17%; and postoperative, 37%). The 5-year survival rate of patients without perioperative transfusion was 36%, whereas that of patients with a transfusion was 25% (P = .04). Perioperative transfusion and intraoperative transfusion were found to be independent poor prognostic factors [relative risk (RR): 1.52 and 1.95, respectively]. The independent factors associated with perioperative transfusion were being female, operation time >420 minutes, portal vein (PV) resection, and preoperative serum hemoglobin (Hb) < 12 mg/dL. As the amount of perioperative transfusion increased, overall survival (OS) decreased.Perioperative transfusion, especially intraoperative transfusion was an independent prognostic factor for survival after PD. Therefore, for patients with periampullary cancer, intraoperative bleeding and operation time should be minimized and preoperative anemia corrected.

Outcomes for Patients with Recurrent Intrahepatic Cholangiocarcinoma After Surgery.

BACKGROUND: This study aimed to analyze the postoperative outcomes for patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to determine the prognostic factors. In addition, this study investigated the effects of various treatment methods for patients with recurrent ICC. METHODS: This retrospective study analyzed the postoperative outcomes and prognostic factors of recurrent ICC that occurred for 81 of 128 patients who underwent hepatic resection for ICC between April 2001 and April 2013. In addition, the outcomes for a number of treatment methods were assessed for patients with recurrent ICC. RESULTS: After resection, the 128 patients with ICC had survival rates of 73 % at 1 year, 52 % at 3 years, and 43 % at 5 years. Recurrent ICC developed in 81 patients (56 men and 25 women) with a median age of 63 years. The median time from initial resection to recurrence was 9 months (range, 0-124 months), and the median survival time after recurrence was 8 months (range, 0-108 months). After recurrence, the overall survival rates were 47 % at 1 year, 23 % at 3 years, and 15 % at 5 years. Multivariate analysis showed disease-free survival time shorter than 1 year and bile duct invasion to be significant prognostic factors. Among the treatment methods, local management such as surgery, transarterial chemoembolization, and radiofrequency ablation were effective in select cases with localized intrahepatic and extrahepatic recurrence. CONCLUSION: Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence.

Celiac axis stenosis as a rare but critical condition treated with pancreatoduodenectomy: report of 2 cases.

We describe 2 cases of patients with loss of hepatic arterial flow during surgery for pancreatic head cancer due to celiac stenosis caused by median arcuate ligament compression. The first case underwent pylorus-resecting pancreatoduodenectomy for pancreatic head cancer. After resection of the gastroduodenal artery, flow in the common hepatic artery disappeared, and celiac axis stenosis was identified. Interventional stent insertion was attempted, however, it failed due to the acute angle of the celiac orifice (os). This problem was resolved by arterial reconstruction. The second case underwent pylorus-preserving pancreatoduodenectomy for pancreatic head cancer and the same phenomenon occurred during the procedure. Interventional stent insertion was also tried; in this patient, however, it failed due to the acute angle of the celiac os. The problem was resolved by changing a femoral approach to a brachial approach, and the stent was inserted into the celiac os successfully.

Two classes of intrahepatic cholangiocarcinoma defined by relative abundance of mutations and copy number alterations.

Intrahepatic cholangiocarcinoma (ICC) is a biliary tree-origin epithelial malignancy in liver with unfavorable clinical outcomes. Systematic genome analyses may advance our understanding of ICC pathogenesis also improving current diagnostic and therapeutic modalities. In this study, we analyzed 17 ICC tumor-vs-matched normal pairs using either whole-exome (n = 7), transcriptome sequencing (n = 7) or both platforms (n = 3). For somatic mutations, we identified recurrent mutations of previously reported genes such as KRAS, TP53, APC as well as epigenetic regulators and those of TGFß signaling pathway. According to the abundance of somatic mutations and DNA copy number alterations (CNA), ten ICC exome cases were distinguished into two classes as those primarily driven by either somatic mutations (M class) or CNAs (C class). Compared to M class ICCs (92-147 somatic mutations; n = 5) with a relative deficit of CNAs, C class ICCs (54-84 mutations; n = 5) harbor recurrent focal CNAs including deletions involving CDKN2A, ROBO1, ROBO2, RUNX3, and SMAD4. We also show that transcriptome sequencing can be used for expression-based ICC categorization but the somatic mutation calling from the transcriptome can be heavily influenced by the gene expression level and potentially, by posttranscriptional modification such as nonsense mediated decay. Along with a substantial level of mutational heterogeneity of ICC genomes, our study reveals previously unrecognized two ICC classes defined by relative abundance of somatic mutations over CNAs or vice versa, which should be considered in the selection of genotyping platforms and sensitive screening of targets for ICC therapeutics.

Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

OBJECTIVE: To develop and validate a model to predict tumor recurrence after living donor liver transplantation (LDLT) (MoRAL) for hepatocellular carcinoma (HCC) beyond the Milan criteria (MC). BACKGROUND: Some subgroups of HCC exceeding the MC experience substantial benefit from LDLT. METHODS: This multicenter study included a total of 566 consecutive patients who underwent LDLT in Korea: the beyond-MC cohort (n = 205, the derivation [n = 92] and validation [n = 113] sets) and the within-MC cohort (n = 361). The primary endpoint was time-to-recurrence. RESULTS: Using multivariate Cox proportional hazard model, we derived the MoRAL score using serum levels of protein induced by vitamin K absence-II and alpha-fetoprotein, which provided a good discriminant function on time-to-recurrence (concordance index = 0.88). Concordance index was maintained similarly on both internal and external validations (mean 0.87 and 0.84, respectively). At cut off of 314.8 (75th percentile value), a low MoRAL score (≤314.8) was associated with significantly longer recurrence-free (versus > 314.8, HR = 5.29, P < 0.001) and overall survivals (HR = 2.59, P = 0.001) in the beyond-MC cohort. The 5-year recurrence-free and overall survival rates of beyond-MC patients with a low MoRAL score were as high as 66.3% and 82.6%, respectively. The within-MC patients with a high MoRAL score showed a higher risk of recurrence than beyond-MC patients with a low MoRAL score (HR = 2.56, P = 0.035). The MoRAL score was significantly correlated with explant histology. CONCLUSIONS: This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.

Upper midline incision for liver resection.

OBJECTIVES: The optimal incision for liver resection in living donors or patients with small tumours should be revisited. This study introduces the upper midline incision (UMI) above the umbilicus for various liver resections using a conventional open-surgery technique. METHODS: A retrospective study based on a prospectively collected database of 308 liver resections performed by a single surgeon was conducted to evaluate the feasibility, safety and applicability of the UMI. RESULTS: From September 2006 to September 2010, this incision was used successfully in 308 consecutive liver resections in all patients with tumours measuring ≤ 5 cm and all living donors without any extension of the incision. The median length of the incision was 16.4 cm (range: 12-20 cm).The median operating time was 189 min (range: 54-305 min). The median postoperative hospital stay was 8 days (range: 6-17 days). One patient died in the postoperative period from heart failure. All other patients fully recovered and returned to their previous level of activity. Over a median follow-up of 31 months (range: 20-68 months), 25 complications (8.1%) developed. Seven wound infections (2.3%) occurred with no incisional hernia. CONCLUSIONS: The UMI can be used safely and effectively in conventional open surgery in various liver resections and should therefore be given priority as the first-line technique in living liver donors and patients with tumours measuring ≤ 5 cm.

Hanging manoeuver for a left hepatectomy using Glisson's approach with a focus on tape position in liver hilum.

BACKGROUND: Successful use of the hanging manoeuver during a hepatic resection requires the tape to be placed anatomically. The aim of this study is to describe the outcomes after variations in tape placement while using the hanging manoeuver during a left hepatectomy. METHODS: A whole cohort in whom the hanging manoeuver was attempted for a left hepatectomy from March 2003 to October 2011 was divided chronologically into three groups based on the tape position in the hilum along the ligamentum venosum (LV); conventionally between the right and left Glisson's pedicles (group 1), at the ventral side of the LV (group 2), and at the dorsal side of the LV (group 3). Patient characteristics, operative outcomes and complications defined using Clavien's classification were compared. RESULTS: A total of 151 patients were enrolled in one of three groups: group 1 (n = 54), group 2 (n = 35), and group 3 (n = 62). The hanging tape was successfully positioned in all patients as planned in the three groups. In group 2 and 3, the hanging manoeuver was continuously applied during a parenchymal transection. The Glisson's pedicle injury during hilar dissection was more common in group 2 (%, 51.4 versus 5.6 in group 1 and 3.2 in group 3; P = 0.001). Group 3 showed a shorter median operative time (min, 151 versus 210 in group 1 and 220 in group 2; P = 0.001), a shorter median hospital stay (days, 7 versus 10 in group 1 and 2; P = 0.012) and a lower complication rate (%, 1.6 versus 13.0 in group 1 and 37.1 in group 2; P = 0.001) without any operative mortality, major morbidity, blood transfusion or reoperation. CONCLUSIONS: The hanging manoeuver had 100% feasibility with good outcomes during a left hepatectomy. The tape should be positioned to surround the left Glisson's pedicle and LV together as this helps to protect the caudate lobe.

Up-regulation of the BTG2 gene in TPA- or RA-treated HL-60 cell lines.

The key pathogenesis of leukemia is the defection of the differentiation processes of hematopoietic stem cells. There are five APRO (anti-proliferative) genes, BTG1, BTG2, BTG3, TOB and TOB2, and it was reported that certain APRO genes are associated with cell differentiation. However, it is still unknown whether APRO genes are related with the differentiation process of blood cells. In this study, we investigated the expression of APRO genes in 12-O-tetra-decanoylphorbol-13-acetate (TPA) or retinoic acid (RA)-treated HL-60 cell lines. Our data show that the expression of the BTG2 gene was increased in 32 nM TPA-treated and 1 microM RA-treated HL-60 cells, but the expression of the BTG1 and BTG3 genes was not increased. The expression of BTG2 in TPA- or RA-treated HL-60 cells was also increased even in the presence of cyclohexamide, which is an inhibitor of translation, implying that the increased expression of BTG2 mRNA did not require the new synthesis of another protein. Notably, the up-regulation of BTG2 in TPA- or RA-treated HL-60 cells was observed prior to the increased expression of p21. Our data show that PKC pathways are uninvolved with the up-regulation of BTG2 in TPA- or RA-treated HL-60 cells. Thus, the up-regulation of BTG2 genes may be involved in the differentiation process of HL-60 cells after TPA or RA treatment. Furthermore, this event occurred prior to p21 expression, implying that the BTG2 expression plays a role at a very early point during the differentiation processes of hematopoietic cells.