Low tube voltage and deep-learning reconstruction for reducing radiation and contrast medium doses in thin-slice abdominal CT: a prospective clinical trial.

OBJECTIVES: To investigate the feasibility of low-radiation dose and low iodinated contrast medium (ICM) dose protocol combining low-tube voltage and deep-learning reconstruction (DLR) algorithm in thin-slice abdominal CT. METHODS: This prospective study included 148 patients who underwent contrast-enhanced abdominal CT with either 120-kVp (600 mgL/kg, n = 74) or 80-kVp protocol (360 mgL/kg, n = 74). The 120-kVp images were reconstructed using hybrid iterative reconstruction (HIR) (120-kVp-HIR), while 80-kVp images were reconstructed using HIR (80-kVp-HIR) and DLR (80-kVp-DLR) with 0.5 mm thickness. Size-specific dose estimate (SSDE) and iodine dose were compared between protocols. Image noise, CT attenuation, and contrast-to-noise ratio (CNR) were quantified. Noise power spectrum (NPS) and edge rise slope (ERS) were used to evaluate noise texture and edge sharpness, respectively. The subjective image quality was rated on a 4-point scale. RESULTS: SSDE and iodine doses of 80-kVp were 40.4% (8.1 ± 0.9 vs. 13.6 ± 2.7 mGy) and 36.3% (21.2 ± 3.9 vs. 33.3 ± 4.3 gL) lower, respectively, than those of 120-kVp (both, p < 0.001). CT attenuation of vessels and solid organs was higher in 80-kVp than in 120-kVp images (all, p < 0.001). Image noise of 80-kVp-HIR and 80-kVp-DLR was higher and lower, respectively than that of 120-kVp-HIR (both p < 0.001). The highest CNR and subjective scores were attained in 80-kVp-DLR (all, p < 0.001). There were no significant differences in average NPS frequency and ERS between 120-kVp-HIR and 80-kVp-DLR (p ≥ 0.38). CONCLUSION: Compared with the 120-kVp-HIR protocol, the combined use of 80-kVp and DLR techniques yielded superior subjective and objective image quality with reduced radiation and ICM doses at thin-section abdominal CT. CLINICAL RELEVANCE STATEMENT: Scanning at low-tube voltage (80-kVp) combined with the deep-learning reconstruction algorithm may enhance diagnostic efficiency and patient safety by improving image quality and reducing radiation and contrast doses of thin-slice abdominal CT. KEY POINTS: Reducing radiation and iodine doses is desirable; however, contrast and noise degradation can be detrimental. The 80-kVp scan with the deep-learning reconstruction technique provided better images with lower radiation and contrast doses. This technique may be efficient for improving diagnostic confidence and patient safety in thin-slice abdominal CT.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.

BACKGROUND & AIMS: There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. METHODS: A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). RESULTS: A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. CONCLUSION: The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification. RESULTS: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-γ-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors. CONCLUSIONS: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.

Major postoperative complications are associated with early recurrence of hepatocellular carcinoma following hepatectomy.

BACKGROUND AND AIM: Early recurrence (ER) is a strong predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. The aim of this study was to examine manageable factors associated with ER. METHODS: Overall, 475 consecutive patients with primary HCC who underwent curative hepatectomy were included (R0/R1). We defined ER as recurrence within 2 years after hepatectomy and analyzed predictors for ER. We also defined postoperative complication as Clavien-Dindo classification grade III or IV. RESULTS: ER after hepatectomy was observed in 209 cases (44.0%). Patients with ER had a significantly poor prognosis compared with those with late recurrence (log-rank p < 0.0001) and were more likely to be diagnosed with extrahepatic metastasis (p = 0.009). Significant predictors for ER were des-γ-carboxyprothrombin > 40 mAU/mL (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.36-3.14, p = 0.001), multiple tumors (OR 2.80 95%CI 1.83-4.32, p < 0.0001), cirrhosis (OR 1.53, 95%CI 1.01-2.32, p = 0.043), and postoperative complications (OR 1.72, 95% CI 1.05-2.85, p = 0.032). Blood loss (OR 1.09, 95%CI 1.05-1.13, p < 0.0001) and cirrhosis (OR 1.74, 95%CI 1.05-2.86, p = 0.031) were significant predictors for postoperative complications. CONCLUSIONS: We should pay close attention to surgical associated- and disease-specific factors in hepatectomy for HCC to prevent ER.

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: High rate of early recurrence and its predictors.

AIM: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a very rare subtype of primary liver carcinoma; therefore, its clinicopathological characteristics have not yet been elucidated in detail. The aim of the study was to reveal the clinicopathological characteristics and prognostic factors of cHCC-CCA after hepatic resection (HR) METHODS: A total of 124 patients who underwent curative HR for cHCC-CCA between 2000 and 2016 were enrolled in this multi-institutional study conducted by the Kyushu Study Group of Liver Surgery. Clinicopathological analysis was performed from the viewpoint of patient prognosis. RESULTS: A total of 62 patients (50%) had early recurrence within 1.5 years after HR, including 36 patients (58%) with extrahepatic recurrence. In contrast, just four patients (3%) had late recurrence occurring >3 years after HR. The independent predictors of early recurrence were as follows: des-gamma carboxyprothrombin >40 mAU/mL (odds ratio 26.2, P = 0.0117), carbohydrate antigen 19-9>37 IU/l (odds ratio 18.0, P = 0.0200), and poorly differentiated HCC or CCA (odds ratio 11.2, P = 0.0259). CONCLUSIONS: Half of the patients with cHCC-CCA had early recurrence after HR. Preoperative elevation of des-gamma carboxyprothrombin or carbohydrate antigen 19-9 and the existence of poorly differentiated components of HCC or CCA in resected specimens are predictors of its early recurrence.

[A Case of Long-Term Survival after Chemotherapy and Ablation Therapy Using Various Approaches for Multiple Colon Cancer Liver Metastases].

A 58-year-old man with unresectable sigmoid colon cancer and multiple liver metastases(H2, more than 30)received chemotherapy for 2 years. Subsequently, the patient was diagnosed with stenosis of the primary lesion and 5 bilobar, metastatic tumors. Simultaneous resection was unsuitable because of the performance status and comorbidities of the patient. The first surgery consisted of laparoscopic-assisted sigmoidectomy, laparoscopic microwave coagulation therapy(MCT), and percutaneous radiofrequency ablation(RFA). Percutaneous RFA was additionally performed after 2 months. Since 2 liver metastases(S3 and S8)were inadequately treated, 3 courses of P-mab plus FOLFIRI were administered. Finally, laparoscopic- assisted RFA was performed. Subsequently, serum CEA reduced from 288.3 ng/mL to the normal level. We used fusion imaging US, sonazoid US, laparoscopic convex probe, and ICG fluorescence imaging for ablation therapy. Chemotherapy and ablation therapy using various approaches can control unresectable multiple liver metastases and prolong survival by more than 3 years.

[A Patient with Multiple Colorectal Liver Metastases for Whom Partial Splenic Embolization Contributed Extremely to Maintain Multidisciplinary Treatment].

After approximately 2.5 years of chemotherapy at the referred hospital, a 69-year-old man with double colon cancer and unresectable liver metastases(H3)sought consultation. A total of 8 liver metastases were deemed resectable; however, the disease was progressive. He received 2 courses of mFOLFOX6 plus Bmab before hepatectomy. Seven weeks after starting chemotherapy, Grade 4 thrombocytopenia occurred, which required platelet transfusion. Ten weeks after, curative parenchymal- preserving hepatectomy was performed under platelet transfusion. Hematologic examination including bone marrow aspiration showed no significant abnormalities, including normal megakaryocyte formation. Therefore, the patient was diagnosed with thrombocytopenia due to sinusoidal obstruction syndrome associated with past chemotherapy including oxaliplatin. Partial splenic embolization(PSE)was performed 8 weeks after the first hepatectomy. The infarcted splenic ratio was 79.5%, and the infarcted splenic volume was 444.3 mL. Curative resection of the primary colorectal cancer and the 2nd hepatectomy for the newly developed recurrent liver lesions was successfully performed at 2 weeks and 19 weeks after PSE, respectively. Platelet transfusion was never required in the perioperative period of the 2 operations performed after the PSE. Forty-five months after the initial treatment, the patient is alive with no recurrent tumors and normal tumor marker levels.

Clinical significance of half-lives of tumor markers α-fetoprotein and des-γ-carboxy prothrombin after hepatectomy for hepatocellular carcinoma.

AIM: The prognostic significance of the half-lives (HLs) of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients. METHODS: This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post-hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis. RESULTS: Three-year recurrence-free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five-year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07). CONCLUSION: Post-hepatectomy HLs of AFP and DCP are predictors of long-term outcome in patients with HCC.

Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma.

BACKGROUND: For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS: Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS: The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS: A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

Shape and Enhancement Characteristics of Pancreatic Neuroendocrine Tumor on Preoperative Contrast-enhanced Computed Tomography May be Prognostic Indicators.

BACKGROUND: Prognostic indicators of the malignant potential of pancreatic neuroendocrine tumors (PNET) are limited. We assessed tumor shape and enhancement pattern on contrast-enhanced computed tomography as predictors of malignant potential. METHODS: Sixty cases of PNET patients undergoing curative surgery from 2001 to 2014 were enrolled onto our retrospective study. Preoperative enhanced CTs were assessed, and criteria defined for regularly shaped and enhancing tumors (group 1), and irregularly shaped and/or enhancing tumors (group 2). The relation of tumor shape and enhancement pattern to outcome was assessed. RESULTS: Interobserver agreement was substantial (kappa = 0.74). Group 2 (n = 24) was significantly correlated with synchronous liver metastasis (23 vs. 0 %), lymph node metastasis (36 vs. 3 %), pathologic capsular invasion (68 vs. 8 %), larger tumor size (30 vs. 12 mm), tumor, node, metastasis classification system (TNM) stage III/IV disease (46 vs. 3 %), and histologic grade 2/3 (41 vs. 0 %). Multivariate analysis revealed that tumor grade 2/3 and group 2 criteria correlated with tumor relapse (hazard ratio 6.5 and 13.6, P = 0.0071 and 0.039, respectively), and that only group 2 criteria were independently correlated with poor overall survival (hazard ratio 5.56e + 9, P = 0.0041). CONCLUSIONS: Irregular tumor shape/enhancement on preoperative computed tomography is a negative prognostic factor after curative surgery for PNET.

Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow.

AIM: Liver is an amazing organ that can undergo regenerative and atrophic changes inversely, depending on blood flow conditions. Although the regenerative mechanism has been extensively studied, the atrophic mechanism remains to be elucidated. METHODS AND RESULTS: To assess the molecular mechanism of liver atrophy due to reduced portal blood flow, we analyzed the gene expressions between atrophic and hypertrophic livers induced by portal vein embolization in three human liver tissues using microarray analyses. Thrombospondin (TSP)-1 is an extracellular protein and a negative regulator of liver regeneration through its activation of the transforming growth factor-ß/Smad signaling pathway. TSP-1 was extracted as the most upregulated gene in atrophic liver compared to hypertrophic liver due to portal flow obstruction in human. Liver atrophic and hypertrophic changes were confirmed by HE and proliferating cell nuclear antigen staining and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling. In an in vivo model with portal ligation, TSP-1 and phosphorylated Smad2 expression were continuously induced at 6 h and thereafter in the portal ligated liver, whereas the induction was transient at 6 h in the portal non-ligated liver. Indeed, while cell proliferation represented by proliferating cell nuclear antigen expression at 48 h was induced in the portal ligated liver, the sinusoidal dilatation and hepatocyte cell death with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was detectable at 48 h in the portal ligated liver. CONCLUSIONS: Obstructed portal flow induces persistent TSP-1 expression and transforming growth factor-ß/Smad signal activation in atrophic liver. Thrombospondin-1 may be implicated in the liver atrophic change due to obstructed portal flow as a pro-atrophic factor.

Preoperative platelet-to-lymphocyte ratio can predict recurrence beyond the Milan criteria after hepatectomy for patients with hepatocellular carcinoma.

AIM: Postoperative recurrence beyond the Milan criteria is a poor prognostic factor for patients with hepatocellular carcinoma (HCC) treated with various therapies. We investigated the most useful inflammation-based prognostic score for predicting recurrence beyond the Milan criteria after initial liver resection. METHODS: From January 2007 to December 2012, 271 consecutive patients with HCC who underwent curative liver resection were enrolled. Patients were divided according to the initial recurrence pattern: recurrence beyond the Milan criteria; and recurrence within the Milan criteria, or no recurrence. The patients were classified into two groups, low platelet-to-lymphocyte ratio (PLR) (<150) and high PLR (≥150), additionally using other inflammation-based prognostic scores. Then we analyzed the association between the recurrence patterns and the clinicopathological factors including PLR. RESULTS: Fifty-five (20.2%) patients had recurrence beyond the Milan criteria. The 5-year survival rate in patients with recurrence beyond the Milan criteria (41.6%) was significantly lower than in those with other recurrence patterns (79.7%). High PLR level was observed in 15.5% of the patients. Multivariate analysis revealed that PLR was the only independent predictive factor of recurrence patterns (odds ratio, 2.55; 95% confidence interval, 1.17-5.49; P = 0.018). The high PLR level was significantly associated with higher serum des-γ-carboxy prothrombin level, larger tumor size, and poor histological differentiation. CONCLUSION: Among several inflammatory indices, PLR is a good indicator to predict recurrence beyond the Milan criteria after liver resection for patients with HCC.

Neutrophil-to-lymphocyte ratio predicts metachronous liver metastasis of pancreatic neuroendocrine tumors.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are clinically malignant, having metastatic potential. Histological tumor grade is an accepted indicator of malignant potential, but noninvasive prognostic markers have not yet been identified. This study assessed whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict clinical outcomes of PNET patients. METHODS: Fifty-eight patients who underwent curative resection for PNETs between 2001 and 2015 were retrospectively evaluated. The correlations between the preoperative NLR and clinicopathological parameters, including patient baseline clinical characteristics, tumor progression, and postoperative oncological outcome were evaluated. RESULTS: A high preoperative NLR was significantly associated with large tumor size (P = 0.0015) and high tumor grade (P < 0.0001). Overall survival and relapse-free survival of patients with a high NLR (≥2.4) were significantly shorter than those of patients with a low NLR (<2.4, P = 0.0481 and P < 0.0001, respectively). Multivariate analysis revealed that NLR ≥2.4 and tumor size ≥2 cm were independent predictors of postoperative recurrence (hazard ratio 6.012, P = 0.0035 and 6.760, P = 0.0049, respectively). Interestingly, a high NLR independently predicted postoperative liver, but not lymph node, metastasis. CONCLUSIONS: In this patient series, a high NLR (≥2.4) was a noninvasive marker that independently predicted postoperative liver metastasis in patients with PNETs, and thereby could be clinically useful.

Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma.

PURPOSES: We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. METHODS: The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. RESULTS: The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P < 0.001), respectively. The 2-year local recurrence rates were 6.5, 0, 41.2, and 61.9 %, respectively (P < 0.001). Multivariate analysis revealed that a double- or triple-positive pre-treatment tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P < 0.001] and overall survival (HR 4.21, 95 % CI 1.89-9.37, P < 0.001). CONCLUSION: RFA may not be suitable for patients with HCC who have pre-treatment expression of ≥two of these tumor markers.

Significance of lymph node metastasis in pancreatic neuroendocrine tumor.

PURPOSE: Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. METHODS: We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. RESULTS: Although the 5-year OS was 74.8% for LNM+ and 94.6% for LNM- (P = 0.002), LNM was not an independent risk factor for the OS in a multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor, and the cut-off value for the predictive score was 1.69. CONCLUSIONS: Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.