Yujiro Nishioka

Effect of Background Liver Cirrhosis on Outcomes of Hepatectomy for Hepatocellular Carcinoma

Importance Background hepatocarcinogenesis is considered a major cause of postoperative recurrence of de novo hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). The degree of underlying liver injury has reportedly correlated with surgical outcomes of HCC. However, the pattern and annual rate of recurrence of postoperative de novo HCC are still unclear. Objective To clarify the pattern and rate of recurrence of de novo HCC in patients with LC. Design, Setting, and Participants Data from 799 patients who underwent curative hepatectomy for HCC at Toranomon Hospital and The Johns Hopkins Hospital between January 1, 1995, and December 31, 2014, were retrospectively collected and analyzed. Of the patients who underwent curative hepatectomy for HCC, 424 met inclusion criteria: 73 with normal liver (NL) and 351 with LC. Sixty-four patients who had histologically proven NL parenchyma were matched with an equal number of patients who had established LC, and postoperative outcomes were compared. Interventions Hepatectomy in patients with HCC. Main Outcomes and Measures Patterns of recurrence of HCC and chronological changes in recurrence rates. Results Among 128 matched patients in the study (mean [SD] age, 64.0 [12.7] years; 93 men and 35 women) 1-, 3-, and 5-year cumulative recurrence was 17.2%, 23.0%, and 37.5%, respectively, in the NL group vs 25.0%, 55.5%, and 72.1%, respectively, in the LC group (P = .001). The 3- and 5-year disease-specific survival was 85.7% and 75.4%, respectively, in the NL group vs 74.9% and 59.1%, respectively, in the LC group (P = .04). The median annual incidence of postoperative recurrence of HCC within 5 years after surgery was lower in the NL group (5.9%) compared with the LC group (12.7%) (P = .003). Assessment of recurrence patterns revealed that multiple recurrences near the resection margin or at extrahepatic sites were more frequent in the NL group (9 [50.0%] vs 6 [15.4%]; P = .01), whereas solitary recurrence at a distant site was more common in the LC group (21 [53.8%] vs 1 [5.6%]; P < .001). Conclusions and Relevance Comparison of the patterns and annual incidence of recurrence of HCC demonstrated that the poorer prognosis in the LC group was likely owing to a higher hepatocarcinogenic potential among patients with cirrhosis. Annual recurrence rates in the 2 groups indicate that de novo recurrence may continuously occur from the early postoperative period until the late period after resection of HCC.

Hemostatic status in liver transplantation: Association between preoperative procoagulants/anticoagulants and postoperative hemorrhaging/thrombosis

The delicate rebalanced hemostatic status of liver transplant recipients may lead to both hemorrhagic and thrombotic tendencies in this population. The aim of this study was to investigate the association between pretransplant procoagulants/anticoagulants and posttransplant bleeding and thrombosis among living donor liver transplant recipients. The study subjects were 403 consecutive recipients with chronic liver disease. Perioperative variables, including preoperative values for procoagulants and anticoagulants, were assessed to determine their association with posttransplant hemorrhaging and thrombosis. There were 35 hemorrhagic complications (9%) and 21 thrombotic complications (5%). In logistic regression analyses, a higher Model for End‐Stage Liver Disease score (P = 0.01) and a lower fibrinogen value (P < 0.001) were independently associated with hemorrhaging, whereas only a lower protein C value (P < 0.001) was independently associated with thrombosis. In a receiver operating characteristic analysis, a low preoperative protein C value (with the most accurate cutoff value being 25%) was a reliable predictor of thrombotic complications after liver transplantation (area under the curve = 0.921, P < 0.001, sensitivity = 0.9, specificity = 0.8). In conclusion, the decreases in both procoagulants and anticoagulants in liver transplant recipients may additively result in a delicate hemostatic balance and predispose patients to both hemorrhagic and thrombotic complications. A lower preoperative protein C value (<25%) was demonstrated to be a significant and reliable predictor of postoperative thrombotic complications in liver transplant recipients. Liver Transpl 21:258‐265, 2015.

Prognostic impact of complications after resection of early stage hepatocellular carcinoma

Resection is the most effective treatment for HCC. However, postoperative morbidity is common and its impact on long‐term oncological outcome remains unclear.

Hereditary Hemorrhagic Telangiectasia with Hepatic Vascular Malformations

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disease. Early diagnosis is important to avoid complications from vascular lesions, but diagnosis is difficult in asymptomatic patients. A 69-year-old Japanese male patient was referred to our hospital for evaluation of hepatic vascular malformations. He had mild anemia with iron deficiency, and dynamic contrast-enhanced computed tomography revealed significant arteriovenous and arterioportal shunts throughout the liver. Telangiectasia from the pharynx to the duodenum was confirmed by gastrointestinal endoscopy. The patient history revealed episodes of epistaxis as well as a family history of epistaxis. He was diagnosed with HHT, although no other family member had been diagnosed with definite HHT. A diagnosis of HHT must be considered in patients with hepatic vascular malformations.

Postoperative low hepatitis C virus load predicts long-term outcomes after hepatectomy for hepatocellular carcinoma

Preoperative hepatitis C virus (HCV) viral load is known to predict long‐term outcomes after hepatectomy for HCV‐related hepatocellular carcinoma (HCC). This study sought to examine the hypothesis that postoperative and preoperative HCV viral‐load have similar prognostic implications, as well as determine a target viral‐load that will improve long‐term postoperative outcomes.

Host MICA Polymorphism as a Potential Predictive Marker in Response to Chemotherapy for Colorectal Liver Metastases

Background: Understanding the genetic background of a tumor is important to better stratify patient prognosis and select optimal treatment. For colorectal liver metastases (CLM), however, clinically available biomarkers remain limited. Methods: After a comprehensive sequencing of 578 cancer-related genes in 10 patients exhibiting very good/poor responses to chemotherapy, the A5.1 variant of the MICA gene was selected as a potential biomarker for CLM. The clinical relevance of MICA A5.1 was then investigated in 58 patients who underwent CLM resection after chemotherapy. Results: The A5.1 variant was observed in 16 (27.6%) patients examined using direct DNA sequencing, and a very high concordance rate (56/58, 96.6%) for the MICA variant was confirmed between tumor tissues and normal liver parenchyma. A multivariate analysis of 38 patients with no history of treatment with anti-EGFR antibodies confirmed that MICA A5.1 was significantly correlated with an optimal CT morphologic response (OR 11.67; 95% CI 2.08–65.60; p = 0.005) and tended to be correlated with a tumor viability of < 20% after chemotherapy (OR 5.91; 95% CI 0.97–36.02; p = 0.054). MICA A5.1 was also associated with a decreased risk of progression after CLM resection. Conclusion: The MICA A5.1 polymorphism was associated with a better CT morphologic response to chemotherapy and a reduced risk of relapse after CLM resection. Given the high concordance rate in MICA variants between normal liver tissue and CLM, the genetic background of the host could be a new biomarker for CLM.

MRI Detection of Intratumoral Fat in Colorectal Liver Metastases After Preoperative Chemotherapy

OBJECTIVE The objective of this study was to investigate the incidence and clinical significance of intratumoral fat deposition in colorectal liver metastases (CLMs) after preoperative chemotherapy using dual-echo gradient-recalled echo MRI. MATERIALS AND METHODS Our institutional review board approved this retrospective radiographic study and waived the requirement for informed patient consent. Fifty-nine patients (33 men, 26 women; median age, 62 years old) who underwent preoperative MRI and curative hepatic resection for colorectal liver metastases after chemotherapy were selected. Twenty patients also underwent MRI before chemotherapy. On dual-echo gradient-recalled echo MR images, intratumoral fat deposition and fat signal fraction at the densest areas of fat deposition in colorectal liver metastases were evaluated. Predictors of overall survival and intratumoral fat deposition after chemotherapy were identified by multivariate analyses. RESULTS Before and after chemotherapy, 0 (0%) and 32 (54%) of the patients exhibited intratumoral fat deposition, respectively. Independent predictors of poor overall survival were presence of five or more CLMs (p < 0.001), fat signal fraction of 12% or more (p = 0.01), age of 65 years or older (p = 0.02), and tumor response classified as progressive or stable disease by the Response Evaluation Criteria in Solid Tumors 1.1 (p = 0.049). Predictors of tumor fat signal fraction being 12% or greater after chemotherapy were largest tumor size of 5 cm or more (p = 0.005), tumor calcification (p = 0.008), and history of cetuximab or panitumumab administration (p = 0.04). CONCLUSION CLMs after preoperative chemotherapy frequently exhibit intratumoral fat deposition.

Bilateral anatomic resection of the ventral parts of the paramedian sectors of the liver with total caudate lobectomy for deeply/centrally located liver tumors: a new technique maximizing both oncological and surgical safety

Systematic resection of the tumor‐bearing portal territory is reportedly correlated with an improved survival of patients with liver tumors, especially in hepatocellular carcinoma. Despite advances in surgical management, however, anatomic resection of deeply/centrally located tumors remains a challenging procedure not only with technical difficulty but also because of decreased hepatic functional reserve frequently observed due to underlying liver disease. In this report, we have reported a novel technique that allows a promising approach for deeply/centrally located tumors with maximizing both the surgical and oncological safety. Bilateral anatomic resection of the ventral parts of the paramedian sectors (BVPM) offers a sufficient surgical window for safe access to the perihilar region. This technique is based on Hjortsjos theory for liver anatomy and enables systematic removal of the 3rd‐order portal territories. In addition, the current technique is advantageous in minimizing the loss of the normal liver parenchyma without leaving ischemia or congestion in the future liver remnant. Of the seven consecutive patients who were treated with this procedure, all the patients achieved R0 resection with acceptable rate of major morbidity (1/7, 14%). The BVPM may offer a safe and maximized chance of curative resection for deeply/centrally located liver tumors.

Prognostic Impact of Adjuvant Chemotherapy after Hepatic Resection for Synchronous and Early Metachronous Colorectal Liver Metastases

Background: Although the usefulness of adjuvant chemotherapy has been established in the treatment for stages II/III colorectal cancer, its prognostic advantage for colorectal liver metastases (CLM) remains controversial. Methods: Two hundred and nine patients who underwent curative resection for CLM were reviewed. The potential advantage of adjuvant chemotherapy was investigated in 3 groups stratified by disease-free interval (DFI): synchronous CLM (S-CLM), early metachronous CLM (EM-CLM, DFI ≤1 year), and late metachronous CLM (LM-CLM, DFI >1 year). Results: Of the 105 patients who underwent adjuvant chemotherapy after surgery, 47 received uracil-tegafur and leucovorin (UFT/LV) while 58 received the oxaliplatin-based regimen. Five-year recurrence-free survival (RFS) rates in patients with/without adjuvant chemotherapy were 32.8/11.2% in S-CLM (p = 0.002), 43.7/15.2% in EM-CLM (p = 0.002), 44.1/29.6% in LM-CLM (p = 0.163), respectively. Five-year overall survival (OS) rates were 77.9/44.5% in S-CLM (p = 0.021), 81.5/39.5% in EM-CLM (p = 0.015), 76.1/65.4% in LM-CLM (p = 0.411), respectively. Multivariate analyses in S-CLM and EM-CLM indicated that adjuvant chemotherapy is correlated with better RFS and OS irrespective of the regimens, while the incidence of severe adverse event was significantly different between UFT/LV and oxaliplatin (6.8 vs. 50.9%, p < 0.0001). Conclusion: Adjuvant chemotherapy might improve the clinical outcomes in S-CLM and EM-CLM. UFT/LV might be a choice for CLM in adjuvant settings in selected patients.

Total bilirubin amount in drainage fluid can be an early predictor for severe biliary fistula after hepatobiliary surgery

The ratio of the bilirubin concentration in abdominal drainage fluid to the serum bilirubin concentration (d-Bil/s-Bil) has been used as a predictor of biliary fistula (BF) formation after hepatobiliary surgery. The d-Bil/s-Bil ratio is highly influenced by the amount of drainage and is not always reliable, especially when the amount of drainage is large. In this study, the usefulness of the d-Bil/s-Bil ratio and total bilirubin amount in the drainage fluid (TBA) (bilirubin concentration in the drainage fluid x the amount of drainage) as predictors of severe BF (sBF) formation was evaluated retrospectively from the data of 306 patients who had undergone hepatobiliary surgery. Of the 306 patients, 201 patients were included in the training set and the remaining 105 in the validation set, to determine the best parameter to predict sBF formation after hepatobiliary surgery. Receiver-operating characteristic curve analysis revealed that the predictive power of TBA was superior to that of the d-Bil/s-Bil ratio throughout the postoperative period, and that the TBA on postoperative day (POD) 1 showed the highest discriminatory power in the training set (area under the curve, 0.789; cutoff value, 470 mg/day). The TBA on POD 1 also showed the highest predictive power for sBF formation in the validation set, with a sensitivity of 100%, specificity of 97.1%, and accuracy of 97.1%. In conclusion, TBA may be a more reliable predictor of sBF than the conventionally used d-Bil/s-Bil ratio. Early prediction of sBF may be useful for early removal of unnecessary prophylactic drainage tubes after hepatobiliary surgery.