Publisher：南江堂  

DOI： 10.15106/j_geka87_182

CiNii Research

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：Surgery Today  

Purpose: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. Methods: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. Results: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31–2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05–1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). Conclusions: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

DOI： 10.1007/s00595-024-02885-z

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：Surgery Today  

Purpose: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. Methods: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. Results: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31–2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05–1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). Conclusions: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

DOI： 10.1007/s00595-024-02885-z

Scopus

PubMed

Publisher：南江堂  

DOI： 10.15106/j_geka86_1288

CiNii Research

Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は78歳女性で、C型肝炎ウイルス抗体陽性を示して紹介受診となった。超音波検査で肝S8に13mmの等エコー病変を認めた。病変は、造影CTではarterial hyperintensityおよび後期相でwashoutを示し、ethoxybenzyl MRIでは動脈相で増強効果の亢進、肝細胞相で低信号を示した。腫瘍マーカーはいずれも正常であったが、CTおよびMRIにおける造影パターンは肝細胞癌と一致していたことから、S8亜区域切除を施行した。切除検体の病理組織検査において、胚中心の拡張を伴うさまざまなサイズおよび形状のdense lymphoid tissueを認めた。免疫組織化学染色ではCD3、CD10(胚中心)、CD20陽性、bcl-2(胚中心)およびEpstein-Barrウイルス陰性を示した。IgH遺伝子再構成のPCR解析ではpolyclonalityを認めた。これらの所見から肝reactive lymphoid hyperplasiaと診断した。術後経過に問題はなく、術後10日目に退院に至った。術後のQOLは良好で、4ヵ月時点で肝結節の再発は認めていない。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

膵管腺癌(PDAC)の根治手術を行った127例を対象とした後向き単施設研究において、至適治療を評価するスコアリングモデルを作成した。術後12ヵ月以内の再発を早期再発(ER)と定義し、術前パラメータによるERの予測能をROC曲線により評価した。全体の43例でERが認められ、ER群では非ER群に比べて予後が有意に不良であった。糖鎖抗原(CA)19-9値、リンパ球-単球比(LMR)が最も強力な診断因子であった。至適カットオフ値を用いてER予測スコアを算出した結果、CA19-9+LMRスコア高値は、全生存、無再発生存の短縮と有意に関連した。多変量解析では、ERの独立した予測因子はCA19-9+LMRスコア高値であった。CA19-9+LMRスコアリングモデルは、切除可能なPDAC患者のリスク層別化に適用可能であると考えられた。

Language：English   Publisher：Surgery Today  

Purpose: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, which causes a poor prognosis. This study aimed to establish a scoring model to assess the optimal treatment in patients who underwent surgery for PDAC. Methods: This single-center retrospective study included 127 patients who underwent radical resection for PDAC between 2005 and 2021. Early recurrence (ER) was defined as recurrence within 12 months after resection. The predictive effect for ER was evaluated using receiver operating characteristic (ROC) curves of preoperative parameters. Results: ER occurred in 43 (33.9%) patients. The ER group had a significantly worse prognosis than the non-ER group (p < 0.0001). The carbohydrate antigen 19-9 (CA19-9) level and lymphocyte-to-monocyte ratio (LMR) were the strongest diagnostic factors (areas under the ROC curves: 0.74 and 0.68, respectively). The ER prediction score was calculated using optimal cutoff values. A higher CA19-9-LMR score was associated with a worse prognosis in terms of the overall and recurrence-free survival (p = 0.0017 and p < 0.0001, respectively). A multivariate analysis identified a high CA19-9-LMR score as an independent predictor of ER. Conclusions: The CA19-9-LMR scoring model can predict ER after surgery and is applicable for risk stratification in the assessment of patients with resectable PDAC.

DOI： 10.1007/s00595-023-02675-z

Scopus

PubMed

Language：English   Publisher：Surgery Today  

Purpose: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, which causes a poor prognosis. This study aimed to establish a scoring model to assess the optimal treatment in patients who underwent surgery for PDAC. Methods: This single-center retrospective study included 127 patients who underwent radical resection for PDAC between 2005 and 2021. Early recurrence (ER) was defined as recurrence within 12 months after resection. The predictive effect for ER was evaluated using receiver operating characteristic (ROC) curves of preoperative parameters. Results: ER occurred in 43 (33.9%) patients. The ER group had a significantly worse prognosis than the non-ER group (p < 0.0001). The carbohydrate antigen 19-9 (CA19-9) level and lymphocyte-to-monocyte ratio (LMR) were the strongest diagnostic factors (areas under the ROC curves: 0.74 and 0.68, respectively). The ER prediction score was calculated using optimal cutoff values. A higher CA19-9-LMR score was associated with a worse prognosis in terms of the overall and recurrence-free survival (p = 0.0017 and p < 0.0001, respectively). A multivariate analysis identified a high CA19-9-LMR score as an independent predictor of ER. Conclusions: The CA19-9-LMR scoring model can predict ER after surgery and is applicable for risk stratification in the assessment of patients with resectable PDAC.

DOI： 10.1007/s00595-023-02675-z

Scopus

PubMed

Language：English   Publisher：Hepatology Research  

Aims: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). Methods and Results: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. Conclusion: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

DOI： 10.1111/hepr.13875

Web of Science

Scopus

PubMed

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

根治的肝切除が施行された肝内胆管細胞癌患者92例を対象とした後ろ向き研究を実施し、FGFR2発現の臨床的意義および予後を評価した。評価項目は臨床病理学的特徴、転帰などとした。患者をFGFR2陽性群18例(男性16例、年齢中央値65歳)、陰性群74例(男性46例、年齢中央値66歳)に分けて検討した。その結果、FGFR2陽性群では男性が多く、血清アルブミン低値であり、癌胎児性抗原が高値であった(p<0.0001、p=0.0355、p=0.0099)。多変量解析の結果、FGFR2陽性群は無病生存率が不良であることが明らかになった(p=0.0002)。最大腫瘍径(≧5cm)、腫瘍局在(傍肝門型)、FGFR2陽性が無病生存の独立した予測因子であった(p=0.0011、p=0.0180、p=0.0029)。両群間で腫瘍浸潤リンパ球に有意差は認められなかった。以上から、FGFR2高発現は肝切除施行原発性胆管癌患者の再発の独立した予測因子であることが示された。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は74歳男性で、膵体部から尾部を占める膵管内乳頭粘液性腫瘍(IPMN)で14年間経過観察されていた。発熱と無痛性閉塞性黄疸のため当科に紹介された。患者は17年前に胃癌で噴門側胃切除術を受けていた。腹部造影CTでは、膵頭部に境界明瞭な約30mmの門脈相を増強した結節を認め、肝内・肝外胆管の著明な拡張を伴っていた。磁気共鳴胆管膵管造影により膵実質に多数の嚢胞性腫瘤と主膵管拡張を認めた。組織学的に膵頭部の膵管腺癌(PDAC)(cT2N0M0、cStage IB)と診断し、膵体部と膵尾部のIPMNを伴っていた。その後、21日サイクルでゲムシタビン+S-1による術前補助化学療法(NAC)を受けたが、全身性NACの影響により全身状態が低下した。手術治療計画は、幽門部を温存する膵全摘術(TP)を継続し、残胃への血液供給を温存する試みであった。TPを残存胃血流の部分的流入・流出部として脾動脈と静脈を温存しながら行い、その後修正Child法を用いて再建を行った。切除標本の病理組織学的検査では膵頭部に浸潤性乳管腺癌(最大径20mm)、膵体部と膵尾部にIPMNを認め、リンパ節転移はなく、手術断端は陰性であった。術後補助化学療法としてS-1単剤療法を受け、8ヵ月間再発を認めなかった。

Language：English   Publisher：Anticancer Research  

Background/Aim: Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. Patients and Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. Results: The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin–platelet index [API; 156.2×albumin (g/dl)+platelet count (×10⁹/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. Conclusion: The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

DOI： 10.21873/anticanres.16337

Scopus

PubMed

Language：English  

DOI： 10.1007/s13691-023-00596-9

PubMed

Language：English   Publisher：Anticancer Research  

Background/Aim: Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. Patients and Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. Results: The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin–platelet index [API; 156.2×albumin (g/dl)+platelet count (×10⁹/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. Conclusion: The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

DOI： 10.21873/anticanres.16337

Scopus

PubMed

Language：English  

DOI： 10.1007/s13691-023-00596-9

PubMed

Language：English   Publisher：Cancer Science  

The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs.

DOI： 10.1111/cas.15644

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：大道学館出版部  

症例は40歳代女性で、マンモグラフィ検診で異常を指摘され当院を受診した。CT検査、骨シンチの結果、cT1cN0M0 Stage 1の乳癌にて右乳房部分切除+センチネルリンパ節生検を施行した。術後3年6ヵ月が経過し、右上肢痛を訴えたためCT検査を施行した。その結果、腋窩リンパ節は腫大しており、US、MRI検査にて腫大リンパ節が腋窩静脈に浸潤している可能性が疑われた。化学療法先行ではなく手術を行うこととし、腫大したリンパ節が腋窩静脈に強固に癒着しており鈍的鋭的に切離した。腋窩郭清範囲はレベルIII、鎖骨下リンパ節まで郭清した。病理結果では広範囲にinvasive carcinomaを認め、scirrhous typeであった。その後、右腋窩から鎖骨上リンパ節領域にかけて放射線照射を行い、放射線照射終了後に術後補助化学療法としてTC療法を施行し経過観察を行った。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

肝内胆管癌(ICC)の腫瘍微小環境(TME)における癌関連線維芽細胞(CAF)および正常線維芽細胞(NF)由来の細胞外小胞(EV)におけるmiRNAプロファイルの差異について検討した。その結果、NF由来のCMおよびEVと比較して、CAF由来のCMおよびEVは、胆管癌細胞株の増殖、遊走、浸潤を促進した。miRNAマイクロアレイ解析により、NF由来のEVと比較してCAF由来のEVでmiR-493-5pが著しく増加していた。miR-493-5pのトランスフェクションは、胆管癌細胞株の増殖、遊走、浸潤を促進した。免疫組織化学染色を76例のICC標本で実施した。その結果、全生存率、無再発生存率ともにコカイン・アンフェタミン調節転写産物プロペプチド(CARTPT)陰性群で有意に悪化していた。単変量解析と多変量解析により、CARTPTの低発現は、全生存率および無再発生存率の独立した予後不良因子であることが示された。以上より、ICCのTMEにおけるCAFは、腫瘍細胞のCARTPTを抑制し、EVのmiR-493-5pを介して腫瘍細胞を促進することが示唆された。

Language：English   Publisher：World Journal of Surgical Oncology  

Background: Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF. Methods: This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors. Results: Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all). Conclusions: The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

DOI： 10.1186/s12957-022-02714-y

Scopus

PubMed

Language：English   Publisher：World Journal of Surgical Oncology  

Background: Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF. Methods: This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors. Results: Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all). Conclusions: The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

DOI： 10.1186/s12957-022-02714-y

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は76歳男性で、2型糖尿病、高血圧、高脂血症の既往があった。転移リンパ節を有する膵頭部の切除可能な膵管腺癌(PDAC)と診断した。同時に膵尾部から約2cmの嚢胞性腫瘤を認め、仮性嚢胞であることが判明した。PDACに対する術前化学療法後、呼吸困難と左下胸部痛を呈した。胸部X線検査で大量の左胸水を認め、胸水検査でアミラーゼ値が非常に高いことが判明した。CTにより、膵尾部仮性嚢胞と左横隔膜を直接つなぐ瘻孔を確認したことから、膵尾部から左胸膜への膵胸膜瘻が示唆された。胸腔ドレナージ、内視鏡的膵管ドレナージ、抗生剤の内科的治療が無効であったため、PDACに対する膵頭十二指腸切除術の前に膵尾部切除術、瘻孔閉鎖術、胸腔鏡下胸膜剥離術を施行した。術後、胸水は消失し、症状は直ちに改善した。

Language：English  

DOI： 10.1007/s13691-022-00555-w

PubMed

Language：English  

DOI： 10.1007/s13691-022-00555-w

PubMed

Language：English   Publisher：Molecular and Clinical Oncology  

The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarci-noma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.

DOI： 10.3892/mco.2022.2564

Web of Science

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

肝細胞癌(HCC)患者の予後予測に有用な種々の術前マーカーの組み合わせを検討した。肝切除を施行されたHCC患者454例を対象に単施設後ろ向き研究を実施し、トレーニングコホート334例と検証コホート120例に分類して、術前マーカーの組み合わせと手術成績との関連を評価した。全生存期間(OS)中央値はトレーニングコホートが9.6年、検証コホートが8.9年、無病生存期間(DFS)中央値はトレーニングコホート、検証コホート共に2.4年であった。予後予測能を評価したROC解析では、さまざまな炎症性マーカー、栄養関連マーカーのうちPrognostic Nutritional Index(PNI)が最も優れていた(曲線下面積[AUC] 0.627)。肝線維化関連マーカーのうちアスパラギン酸アミノトランスフェラーゼ/血小板比指数(APRI)が最も優れていた(AUC 0.646)。PNIとAPRIを組み合わせたPNI-APRIスコアは検証コホートのDFS不良の予測に関して最も精度が高かった。多変量Cox回帰分析では、検証コホートにおいてPNI-APRI高値がOSおよびDFS不良の独立予測因子であった。以上より、PNI-APRIスコアはHCC患者の術後転帰予測に有用であることが示された。

Language：English   Publisher：Surgery Today  

Purpose: Inflammation-, nutrition-, and liver fibrosis-related markers are recognized as prognostic for hepatocellular carcinoma (HCC) patients. This study, therefore, assessed the preoperative prognostic utility of the combination of these markers in patients with HCC. Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2004 and 2017. A total of 454 patients were divided into training (n = 334) and validation (n = 120) cohorts by random sampling. The predictive impact on surgical outcomes was evaluated using receiver operating characteristic (ROC) curves of these prognostic values in the training cohort. Results: The prognostic nutritional index (PNI) and aspartate aminotransferase-to-platelet ratio index (APRI) were the strongest diagnostic values (areas under the ROC curves: 0.627 and 0.646, respectively). A scoring system (over 0–2 points) was developed using optimal cutoff values (for PNI < 46.5 scored as 1 point; for APRI > 0.98 scored as 1 point). An increased PNI-APRI score was an independent prognostic factor for both the overall and disease-free survival in HCC patients. Finally, the clinical feasibility of the PNI-APRI score was confirmed in the validation cohort. Conclusions: The PNI-APRI score is a useful marker for predicting surgical outcomes of HCC patients.

DOI： 10.1007/s00595-021-02440-0

Scopus

PubMed

Language：English   Publisher：Surgery Today  

Purpose: Inflammation-, nutrition-, and liver fibrosis-related markers are recognized as prognostic for hepatocellular carcinoma (HCC) patients. This study, therefore, assessed the preoperative prognostic utility of the combination of these markers in patients with HCC. Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2004 and 2017. A total of 454 patients were divided into training (n = 334) and validation (n = 120) cohorts by random sampling. The predictive impact on surgical outcomes was evaluated using receiver operating characteristic (ROC) curves of these prognostic values in the training cohort. Results: The prognostic nutritional index (PNI) and aspartate aminotransferase-to-platelet ratio index (APRI) were the strongest diagnostic values (areas under the ROC curves: 0.627 and 0.646, respectively). A scoring system (over 0–2 points) was developed using optimal cutoff values (for PNI < 46.5 scored as 1 point; for APRI > 0.98 scored as 1 point). An increased PNI-APRI score was an independent prognostic factor for both the overall and disease-free survival in HCC patients. Finally, the clinical feasibility of the PNI-APRI score was confirmed in the validation cohort. Conclusions: The PNI-APRI score is a useful marker for predicting surgical outcomes of HCC patients.

DOI： 10.1007/s00595-021-02440-0

Scopus

PubMed

Language：English   Publisher：Hepatology Communications  

We examined phosphorylated nuclear factor erythroid 2–related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.

DOI： 10.1002/hep4.1838

Web of Science

Scopus

PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. Methods: This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. Results: Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. Conclusions: Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

DOI： 10.1245/s10434-021-11011-z

Scopus

PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. Methods: This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. Results: Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. Conclusions: Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

DOI： 10.1245/s10434-021-11011-z

Scopus

PubMed

Language：English   Publisher：Oncology Letters  

The clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8+ T-cell infiltration in hepatocellular carcinoma (HCC) are poorly understood. The present study examined MDSC and CD8+ T-cell infiltration in surgically resected primary HCC specimens and investigated the association of MDSC and CD8+ T-cell infiltration with clinicopathological features and patient outcomes. Using a database of 466 patients who underwent hepatic resection for HCC, immunohistochemical staining of CD33 (an MDSC marker) and CD8 was performed. High infiltration of MDSCs within the tumor was observed in patients with a poorer Barcelona Clinic Liver Cancer stage, larger tumor size, more poorly differentiated HCC, and greater presence of portal venous thrombosis, microscopic vascular thrombosis and macroscopic intrahepatic metastasis. MDSC infiltration and CD8+ T-cell infiltration were independent predictors of recurrence-free survival and overall survival, respectively. Stratification based on the MDSC and CD8+ T-cell status of the tumors was also associated with recurrence-free survival (10 year-recurrence-free survival; MDSChighCD8+ T-cellLow, 3.68%; others, 25.7%) and overall survival (10 year-overall survival; MDSChighCD8+ T-cellLow, 12.0%; others, 56.7%). In conclusion, the present large cohort study revealed that high MDSC infiltration was associated with a poor clinical outcome in patients with HCC. Furthermore, the combination of the MDSC and tumor-infiltrating CD8+ T-cell status enabled further classification of patients based on their outcomes.

DOI： 10.3892/ol.2022.13213

Web of Science

Scopus

PubMed

Language：English   Publisher：Journal of Gastrointestinal Surgery  

Background: Systemic inflammation-related factors, either independently or in combination, are recognized as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte–CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of the LCR in patients with hepatocellular carcinoma (HCC). Methods: This was a single-center retrospective study of patients who underwent surgical resection for HCC between 2004 and 2017. Patients were divided into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Results: A total of 454 patients with HCC were enrolled and assigned to the high- (n=245) or low- (n=209) LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly lower serum albumin level (median 4.1 vs. 3.9 g/dL, P <0.0001), lower platelet count (median 14.0 vs. 12.0 ×10⁴/μL, P=0.0468), lower prothrombin time (median 93.2 vs. 89.6 %, P=0.0006), and larger tumor size (median 2.3 vs. 2.5 cm, P=0.0056). Patients with low-LCR status had significantly worse outcomes of overall survival and disease-free survival than patients with high-LCR status (P=0.0003 and P=0.0069, respectively). Low-LCR status was significantly associated with worse overall survival in multivariate analysis (hazard ratio 1.57, 95% confidence interval 1.14–2.17, P=0.0058). Conclusions: Low-LCR status may predict worse outcomes in patients with HCC. Measurement of LCR is routine and can easily be applied for risk stratification in the assessment of patients with HCC.

DOI： 10.1007/s11605-021-05085-z

Scopus

PubMed

Language：English   Publisher：Journal of Gastrointestinal Surgery  

Background: Systemic inflammation-related factors, either independently or in combination, are recognized as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte–CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of the LCR in patients with hepatocellular carcinoma (HCC). Methods: This was a single-center retrospective study of patients who underwent surgical resection for HCC between 2004 and 2017. Patients were divided into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Results: A total of 454 patients with HCC were enrolled and assigned to the high- (n=245) or low- (n=209) LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly lower serum albumin level (median 4.1 vs. 3.9 g/dL, P <0.0001), lower platelet count (median 14.0 vs. 12.0 ×10⁴/μL, P=0.0468), lower prothrombin time (median 93.2 vs. 89.6 %, P=0.0006), and larger tumor size (median 2.3 vs. 2.5 cm, P=0.0056). Patients with low-LCR status had significantly worse outcomes of overall survival and disease-free survival than patients with high-LCR status (P=0.0003 and P=0.0069, respectively). Low-LCR status was significantly associated with worse overall survival in multivariate analysis (hazard ratio 1.57, 95% confidence interval 1.14–2.17, P=0.0058). Conclusions: Low-LCR status may predict worse outcomes in patients with HCC. Measurement of LCR is routine and can easily be applied for risk stratification in the assessment of patients with HCC.

DOI： 10.1007/s11605-021-05085-z

Scopus

PubMed

Language：English   Publishing type：Doctoral thesis  

収集根拠 : 博士論文（送信）

DOI： 10.1016/j.ejso.2020.08.002

CiNii Research

Language：English   Publishing type：Doctoral thesis  

収集根拠 : 博士論文（送信）

DOI： 10.1016/j.ejso.2020.08.002

CiNii Research

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