論文 - 北郷　実

ASO Author Reflections: Indication Criteria for Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma.

Shimane G, Kitago M, Kitagawa Y

Annals of surgical oncology 32 （ 4 ） 2866 - 2867 2025年04月

ISSN  1068-9265

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Clinical Impact of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Study.

Shimane G, Kitago M, Yagi H, Abe Y, Hasegawa Y, Hori S, Tanaka M, Tsuzaki J, Yokoyama Y, Masugi Y, Takemura R, Kitagawa Y

Annals of surgical oncology 32 （ 4 ） 2830 - 2840 2025年04月

ISSN  1068-9265

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Background: Neoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable. Objective: This study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC. Methods: We retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores. Results: Overall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤.5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0–1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group. Conclusions: Prognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.

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Potential New Tumors Associated with Hereditary Breast and Ovarian Cancer (HBOC).

Nakamura K, Masuda K, Seki T, Kitago M, Kosaka T, Goto Y, Yamada M, Misu K, Ono I, Kobayashi Y, Yamagami W

The Keio journal of medicine 2025年03月

ISSN  0022-9717

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ASO Visual Abstract: The Composite Endpoint of Liver Surgery CELS-Development and Validation of a Clinically Relevant Endpoint Requiring Lower Sample Size.

Kawashima J, Akabane M, Endo Y, Woldesenbet S, Khalil M, Sahara K, Ruzzenente A, Aldrighetti L, Bauer TW, Marques HP, Lopes R, Oliveira S, Martel G, Popescu I, Weiss MJ, Kitago M, Poultsides G, Sasaki K, Maithel SK, Hugh T, Gleisner A, Aucejo F, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM

Annals of surgical oncology 2025年03月

ISSN  1068-9265

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ASO Visual Abstract: The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma.

Kawashima J, Endo Y, Woldesenbet S, Khalil M, Akabane M, Cauchy F, Shen F, Maithel S, Popescu I, Kitago M, Weiss MJ, Martel G, Pulitano C, Aldrighetti L, Poultsides G, Ruzzente A, Bauer TW, Gleisner A, Marques H, Koerkamp BG, Endo I, Pawlik TM

Annals of surgical oncology 2025年03月

ISSN  1068-9265

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Analysis of a modified surgical desirability of outcome ranking (mDOOR) among patients undergoing surgery for Hepatocellular carcinoma.

Catalano G, Alaimo L, Chatzipanagiotou OP, Ruzzenente A, Aucejo F, Marques HP, Lam V, Hugh T, Bhimani N, Kitago M, Endo I, Martel G, Popescu I, Cauchy F, Poultsides GA, Gleisner A, Pawlik TM

HPB : the official journal of the International Hepato Pancreato Biliary Association 2025年03月

ISSN  1365-182X

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Predicting the complexity of minimally invasive liver resection for hepatocellular carcinoma using machine learning.

Catalano G, Alaimo L, Chatzipanagiotou OP, Ruzzenente A, Ratti F, Aldrighetti L, Marques HP, Cauchy F, Lam V, Poultsides GA, Hugh T, Popescu I, Alexandrescu S, Martel G, Kitago M, Endo I, Gleisner A, Shen F, Pawlik TM

HPB : the official journal of the International Hepato Pancreato Biliary Association 2025年03月

ISSN  1365-182X

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ASO Visual Abstract: Advantage of Log Odds of Positive Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Catalano G, Alaimo L, Chatzipanagiotou OP, Ruzzenente A, Aucejo F, Marques HP, Bhimani N, Hugh T, Maithel SK, Kitago M, Endo I, Pawlik TM

Annals of surgical oncology 32 （ 3 ） 1839 - 1840 2025年03月

ISSN  1068-9265

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Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Catalano G, Alaimo L, Chatzipanagiotou OP, Ruzzenente A, Aucejo F, Marques HP, Bhimani N, Hugh T, Maithel SK, Kitago M, Endo I, Pawlik TM

Annals of surgical oncology 32 （ 3 ） 1742 - 1751 2025年03月

ISSN  1068-9265

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Background: Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. Patients and Methods: In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Results: Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5–2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequate LND (< 6 LN) (C index: 0.87). An online calculator was developed (https://catalano-giovanni.shinyapps.io/LoddsGBC/). Conclusions: A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.

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Textbook outcome in liver surgery for intrahepatic cholangiocarcinoma: defining predictors of an optimal postoperative course using machine learning.

Altaf A, Khalil M, Akabane M, Rashid Z, Kawashima J, Zindani S, Ruzzenente A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Popescu I, Weiss MJ, Kitago M, Poultsides G, Maithel SK, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM

HPB : the official journal of the International Hepato Pancreato Biliary Association 27 （ 3 ） 402 - 413 2025年03月

ISSN  1365-182X

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Background: We sought to define textbook outcome in liver surgery (TOLS) for intrahepatic cholangiocarcinoma (ICC) by considering the implications of perioperative outcomes on overall survival (OS). Methods: Using a multi-institutional database, TOLS for ICC was defined by employing novel machine learning (ML) models to identify perioperative factors most strongly predictive of OS ≥ 12 months. Subsequently, clinicopathologic factors associated with achieving TOLS were investigated. Results: A total of 1556 patients with ICC were included. The ML classification models demonstrated that the absence of post-hepatectomy liver failure, intraoperative blood loss <750 mL, absence of major infectious complications, and R0 resection were the perioperative outcomes associated with prolonged OS, thereby defining TOLS for ICC. On multivariable analysis, older age, ASA class >2, lymph node metastasis, receipt of neoadjuvant therapy, advanced T status, poor histological grade and microvascular invasion were independently associated with lower odds of achieving TOLS (all p-values<0.05). Overall, 60.2 % (n = 936) of the patients achieved TOLS, demonstrating markedly improved OS and recurrence-free survival (RFS) than individuals who did not (both p < 0.05). Conclusion: A standardized definition of TOLS for ICC was established that may be used to evaluate hospital performance at the patient level and help optimize surgical outcomes for patients with ICC.

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Upfront surgery for intrahepatic cholangiocarcinoma: Prediction of futility using artificial intelligence.

Altaf A, Endo Y, Guglielmi A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Alexandrescu S, Weiss MJ, Kitago M, Poultsides G, Maithel SK, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM

Surgery 179   108809 2025年03月

ISSN  0039-6060

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Objective: We sought to identify patients at risk of “futile” surgery for intrahepatic cholangiocarcinoma using an artificial intelligence (AI)–based model based on preoperative variables. Methods: Intrahepatic cholangiocarcinoma patients who underwent resection between 1990 and 2020 were identified from a multi-institutional database. Futility was defined either as mortality or recurrence within 12 months of surgery. Various machine learning and deep learning techniques were used to develop prediction models for futile surgery. Results: Overall, 827 intrahepatic cholangiocarcinoma patients were included. Among 378 patients (45.7%) who had futile surgery, 297 patients (78.6%) developed intrahepatic cholangiocarcinoma recurrence and 81 patients (21.4%) died within 12 months of surgical resection. An ensemble model consisting of multilayer perceptron and gradient boosting classifiers that used 10 preoperative factors demonstrated the highest accuracy, with areas under receiver operating characteristic curves of 0.830 (95% confidence interval 0.798–0.861) and 0.781 (95% confidence interval 0.707–0.853) in the training and testing cohorts, respectively. The model displayed sensitivity and specificity of 64.5% and 80.0%, respectively, with positive and negative predictive values of 73.1% and 72.7%, respectively. Radiologic tumor burden score, serum carbohydrate antigen 19-9, and direct bilirubin levels were the factors most strongly predictive of futile surgery. The artificial intelligence–based model was made available online for ease of use and clinical applicability (https://altaf-pawlik-icc-futilityofsurgery-calculator.streamlit.app/). Conclusion: The artificial intelligence ensemble model demonstrated high accuracy to identify patients preoperatively at high risk of undergoing futile surgery for intrahepatic cholangiocarcinoma. Artificial intelligence–based prediction models can provide clinicians with reliable preoperative guidance and aid in avoiding futile surgical procedures that are unlikely to provide patients long-term benefits.

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Dynamic ALBI score and FIB-4 index trends to predict complications after resection of hepatocellular carcinoma: A K-means clustering approach.

Akabane M, Kawashima J, Altaf A, Woldesenbet S, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 51 （ 6 ） 109723 2025年02月

ISSN  0748-7983

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Background: Severe postoperative complications still occur following hepatectomy among patients with hepatocellular carcinoma (HCC). There is a need to identify high-risk patients for severe complications to enhance patient safety. We sought to evaluate the combined impact of pre- and postoperative albumin-bilirubin (ALBI) score and Fibrosis-4 (FIB-4) index trends to predict severe complications after HCC resection. Method: Patients with HCC undergoing curative-intent hepatectomy (2000–2023) were identified from an international, multi-institutional database. The cohort was divided into training (n = 439) and testing (n = 651) sets. ALBI score and FIB-4 index trends from preoperative to postoperative days 1, 3, and 5 were used for K-means clustering (K = 3). A logistic regression model was developed using the training set, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both cohorts. Results: Severe complications (Clavien-Dindo Grade ≥ IIIa) occurred in 118 patients (10.8 %); 43 (9.8 %) in training and 75 (11.5 %) in testing set (p = 0.42). K-means clustering identified three groups: Cluster1 (low), Cluster2 (intermediate), and Cluster3 (high), which was associated with a progressively increasing risk of complications (p < 0.01). On multivariable logistic regression, patients in ALBI Cluster1 had 76 % decreased odds (odds ratio[OR] 0.24, 95 % CI 0.07–0.83, p = 0.02) of postoperative complications relative to Cluster3 patients. Individuals categorized into FIB-4 Cluster1 had 85 % decreased odds (OR 0.15, 95 % CI 0.02–1.24, p = 0.07) versus patients in FIB-4 Cluster3. A new prediction model incorporating ALBI and FIB-4 index clusters achieved an AUC of 0.71, outperforming models based on preoperative data. A tool was made available at https://nm49jf-miho-akabane.shinyapps.io/HCC_ALBI/. Conclusion: A dynamic ALBI score and FIB-4 index trend tool improved risk stratification of patients undergoing resection of HCC relative to severe complications.

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Recurrence patterns and prediction of survival after recurrence for gallbladder cancer.

Catalano G, Alaimo L, Chatzipanagiotou OP, Rashid Z, Kawashima J, Ruzzenente A, Aucejo F, Marques HP, Bandovas J, Hugh T, Bhimani N, Maithel SK, Kitago M, Endo I, Pawlik TM

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 29 （ 4 ） 101997 2025年02月

ISSN  1091-255X

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Background: Gallbladder cancer (GBC) is associated with a poor prognosis. Recurrence patterns and their effect on survival remain ill-defined. This study aimed to analyze recurrence patterns and develop a machine learning (ML) model to predict survival after recurrence (SAR) of GBC. Methods: Patients who underwent curative-intent resection of GBC between 1999 and 2022 were identified using an international database. An Extreme Gradient Boosting ML model to predict SAR was developed and validated. Results: Among 348 patients, 110 (31.6%) developed disease recurrence during follow-up. The most common recurrence site was local (29.1%), followed by multiple site (26.4%), liver (21.8%), peritoneal (18.2%), and lung (0.05%). The median SAR was the longest in patients with lung recurrence (36.0 months), followed by those with local recurrence (15.7 months). In contrast, patients with peritoneal (8.9 months), liver (8.5 months), or multiple-site (6.4 months) recurrence had a considerably shorter SAR. Patients with multiple-site recurrence had a worse SAR than individuals with single-site recurrence (6.4 vs 11.10 months, respectively; P =.014). The model demonstrated good performance in the evaluation and bootstrapping cohorts (area under the receiver operating characteristic curve: 71.4 and 71.0, respectively). The most influential variables were American Society of Anesthesiologists classification, local recurrence, receipt of adjuvant chemotherapy, American Joint Committee on Cancer T and N categories, and developing early disease recurrence (<12 months). To enable clinical applicability, an easy-to-use calculator was made available (https://catalano-giovanni.shinyapps.io/SARGB). Conclusion: Except for lung recurrence, SAR for GBC was poor. A subset of patients with less aggressive disease biology may have favorable SAR. ML-based SAR prediction may help individuate candidates for curative re-resection when feasible.

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The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma.

Kawashima J, Endo Y, Woldesenbet S, Khalil M, Akabane M, Cauchy F, Shen F, Maithel S, Popescu I, Kitago M, Weiss MJ, Martel G, Pulitano C, Aldrighetti L, Poultsides G, Ruzzente A, Bauer TW, Gleisner A, Marques H, Groot Koerkamp B, Endo I, Pawlik TM

Annals of surgical oncology 2025年02月

ISSN  1068-9265

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Introduction: While postoperative adjuvant chemotherapy (AC) is generally recommended for intrahepatic cholangiocarcinoma (ICC), its benefit remains debated. This study aimed to identify patients that may benefit from AC following liver resection of ICC. Methods: Patients who underwent liver resection for ICC between 2000 and 2023 were identified from an international multi-institutional database. Individual multivariable Cox models were used to evaluate the interaction between each prognostic factor and the effect of AC on survival. Results: Among 1412 patients, 431 (30.5%) received AC. Both higher tumor burden score (TBS; hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91–1.00; p = 0.033) and metastatic lymph node status (HR 0.58, 95% CI 0.38–0.89; p = 0.014) demonstrated interactions with the survival benefit from receipt of AC. Interaction plots highlighted how AC was associated with improved survival beyond a TBS of approximately 6. Notably, among 555 (39.3%) patients with TBS <6 and N0 or Nx status, 5-year overall survival (OS) was no different between patients who received AC versus individuals who did not (55.1% [95% CI 48.9–62.1] vs. 58.7% [95% CI 49.8–69.2]; p = 0.900). In contrast, among 857 (60.7%) patients with TBS ≥6 or N1 status, AC was associated with improved 5-year OS (30.7% [95% CI 26.2–36.0] vs. 33.0% [95% CI 26.9–40.5]; p = 0.018). Conclusions: TBS and lymph node status may be useful in a multidisciplinary setting to inform decisions about AC planning for ICC patients following curative-intent resection.

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Impact of disparity between imaging and pathological tumor size on cancer-specific prognosis among patients with hepatocellular carcinoma.

Akabane M, Kawashima J, Altaf A, Woldesenbet S, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 51 （ 6 ） 109683 2025年02月

ISSN  0748-7983

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Background: The association between preoperative imaging and postoperative pathological tumor size disparity, and cancer-specific survival (CSS) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains unclear. We sought to evaluate this association and identify predictors of size disparity. Method: Patients undergoing curative-intent hepatectomy for HCC (2000–2023) were identified from an international, multi-institutional database. Size ratio was defined as the ratio of pathological to imaging tumor size. Patients with a size ratio of 0.5–1.5 were classified as “without size disparity,” while patients outside this range were considered “with size disparity.” Multivariable Cox regression was used to identify predictors of CSS, while logistic regression was utilized to determine factors associated with size disparity. For variables identified as significant in multivariable analyses, further evaluation including cutoff determination, were performed using receiver operating characteristic (ROC) analysis. Results: Among 833 patients, median size ratio was 1.02, with a strong correlation between imaging and pathological tumor sizes (r = 0.87). Size disparity was present in 106 patients (12.7 %); in general, patients had smaller median imaging sizes (2.85 vs. 4.80 cm; p < 0.001) while size on pathology was noted to be larger(both 4.50 cm; p = 0.370). Patients with size disparity had worse 5-year CSS (60.1% vs. 79.0 %; p < 0.001). Multivariable Cox regression identified higher ALBI score (HR:2.56 [1.50–4.37]; p < 0.001), larger pathological tumor size (HR:1.09 [1.03–1.15]; p = 0.001), and size disparity (HR:2.53 [1.37–4.66]; p = 0.002) as independent predictors of CSS. Logistic regression demonstrated that cirrhosis (OR: 2.68 [1.43–5.02]; p = 0.002) and log alpha-fetoprotein (AFP) (OR:1.11 [1.01–1.22]; p = 0.030) were associated with an increased likelihood of size disparity. Cirrhosis and log AFP could be used to stratify patients relative to probability of a size disparity (low-risk:9.9 %, medium-risk:12.2 %, high-risk:17.7 %). The optimal AFP cutoff value was 3928 ng/mL for non-cirrhotic (AUC:0.90) versus 28.9 ng/mL for cirrhotic (AUC:0.74) patients. Conclusion: Tumor size disparity was associated with worse CSS among patients with HCC undergoing hepatectomy. Size disparity could be predicted preoperatively using cirrhosis status and AFP level, which may help identify high-risk patients who may benefit from more detailed imaging assessments.

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Development and validation of the albumin-bilirubin gamma-glutamyl transferase score for enhanced prognostic accuracy after hepatocellular carcinoma resection.

Akabane M, Kawashima J, Altaf A, Woldesenbet S, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 29 （ 4 ） 101984 2025年02月

ISSN  1091-255X

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Background: The albumin-bilirubin (ALBI) score, used for predicting outcomes after hepatocellular carcinoma (HCC) resection, does not directly capture liver cell damage or biliary obstruction. Gamma-glutamyl transferase (GGT), which reflects hepatic oxidative stress and inflammation, may complement the ALBI score. We sought to develop the ALBI-GGT score, a composite prognostic tool, and evaluate its performance to predict long-term outcomes among patients undergoing HCC resection. Methods: Patients undergoing curative-intent HCC resection (2000–2023) were identified from an international, multi-institutional database. The cohort was divided into training (65%) and testing cohorts (35%). Multivariable Cox analysis examined the association of ALBI-GGT score with overall survival (OS). Results: Among 759 patients, the median ALBI score was −2.78 (−3.02 to −2.48), and the median GGT was 55.0 U/L (31.0–93.0). On multivariable analysis, ALBI score (hazard ratio [HR], 1.473 [1.112–1.950]; P =.007) and GGT (HR, 1.007 [1.004–1.010]; P <.001) were predictors of overall mortality, alongside tumor burden score (HR, 1.051 [1.015–1.090]; P =.006) and American Society of Anesthesiologists class >2 (HR, 1.473 [1.005–2.161]; P =.047). There was a near-linear correlation between increasing ALBI scores and GGT and higher hazards of death. The ALBI-GGT score demonstrated the highest predictive accuracy in the testing set (concordance index, 0.68 [0.58–0.72]), outperforming the ALBI score (0.62 [0.56–0.69]) and GGT (0.65 [0.58–0.72]). The ALBI-GGT achieved the lowest Akaike and Bayesian information criteria. Time-dependent area under the curve (AUC) analysis demonstrated consistent superiority over 0 to 60 months. At 1-, 3-, and 5-years, the ALBI-GGT score had AUCs of 0.782, 0.725, and 0.688, respectively, outperforming ALBI score and GGT. The ALBI-GGT score was able to stratify patients into distinct prognostic groups (5-year OS, low ALBI-GGT [85.0%] vs intermediate ALBI-GGT [65.8%] vs high ALBI-GGT [56.8%]; P <.001). Conclusion: ALBI score alone may be insufficient to prognostically stratify patients with HCC. Combining ALBI score with GGT was a superior tool to stratify patients relative to long-term survival.

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Impact of intraoperative blood loss on postoperative morbidity after liver resection for primary and secondary liver cancer.

Altaf A, Akabane M, Khalil M, Rashid Z, Zindani S, Kawashima J, Ruzzenente A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Popescu I, Weiss MJ, Kitago M, Poultsides G, Maithel SK, Lam V, Hugh T, Gleisner A, Sasaki K, Aucejo F, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM

HPB : the official journal of the International Hepato Pancreato Biliary Association 2025年02月

ISSN  1365-182X

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Background: We sought to determine the association between intraoperative blood loss (IBL) and postoperative morbidity among patients undergoing surgery for liver cancer. Methods: Patients undergoing surgery for primary and secondary liver cancer were identified from a multi-institutional database. Adjusted blood loss (aBL) was calculated by normalizing IBL to body weight; the comprehensive complication index (CCI) was used to evaluate postoperative complications. Results: A total of 2491 patients were included. Mean CCI was 10.6 (±5.2) for patients with aBL <10 mL/kg versus 15.2 (±7.2) for individuals with aBL ≥10 mL/kg (p < 0.001). On cubic spline regression, a nonlinear correlation between aBL and CCI was observed. CCI increased exponentially for aBL ranging from 5 to 10 mL/kg, then reached a plateau between an aBL of 10–30 mL/kg before dramatically increasing for aBL >30 mL/kg. Recursive partitioning technique demonstrated that an aBL threshold of 8.5 mL/kg best distinguished CCI (p < 0.001). Additionally, patients with an aBL ≥8.5 mL/kg had worse recurrence-free and overall survival versus patients with an aBL <8.5 mL/kg. Conclusion: A nonlinear incremental correlation between aBL and CCI was identified among patients undergoing surgery for liver cancer. Maintaining an aBL <8.5 mL/kg during LR may help reduce postoperative morbidity.

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Analyzing the interaction between time to surgery and tumor burden score in hepatocellular carcinoma.

Akabane M, Kawashima J, Woldesenbet S, Altaf A, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 29 （ 2 ） 101903 2025年02月

ISSN  1091-255X

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Background: The effect of “time to surgery (TTS)” on outcomes for curative-intent hepatectomy of hepatocellular carcinoma (HCC) remains debated. The interaction between tumor burden score (TBS) and TTS remains unclear. We sought to evaluate the effects of TBS and TTS on long-term HCC outcomes. Methods: Patients with HCC who underwent curative-intent hepatectomy (2000–2022) were analyzed from a multi-institutional database and categorized by TTS (≤60 or >60 days). Overall survival (OS) and cancer-specific survival were assessed. Results: Among 910 patients, median TTS estimates were 22 days in the short TTS group (n = 485) and 120 days in the long TTS group (n = 425). Patients with long TTS were older and were more likely to have American Society of Anesthesiologists class >2, diabetes mellitus, and cirrhosis. There was no difference in median TBS among patients who had short versus long TTS (4.61 vs 5.00, respectively). In addition, there was no difference in 5-year OS (70.0% vs 63.1%, respectively; P =.05). On multivariate analysis TBS (hazard ratio [HR], 1.07; 95% CI, 1.03–1.11; P <.001), log alpha-fetoprotein (HR, 1.08; 95% CI, 1.01–1.14; P =.02), and albumin-bilirubin score (HR, 2.52; 95% CI, 1.66–3.82; P <.001) were associated with OS. In contrast, TTS was not associated with OS (HR, 1.18; 95% CI, 0.78–1.77; P =.43). Interaction analysis demonstrated that TBS was asssociated with OS among patients with short TTS (HR, 1.12; 95% CI, 1.07–1.17; P <.001), but not among patients with long TTS (HR, 0.98; 95% CI, 0.91–1.05; P =.56). Among patients with low TBS (≤5), higher mortality was observed with long TTS versus short TTS (5-year OS: 82.4% vs 63.0%, respectively; P =.001); however, TTS was not associated with OS among patients with high TBS (5-year OS: 57.9% vs 63.3%, respectively; P =.92). Multivariate analysis demonstrated that long TTS was a risk factor for OS among patients with low TBS (HR, 3.12; 95% CI, 1.60–6.01; P <.001), but not among individuals with high TBS (HR, 0.57; 95% CI, 0.30–1.07; P =.08). Similar trends were observed relative to cancer-specific survival. Conclusion: TTS needs to be considered in light of patient and tumor-specific factors. Expediting TTS may be particularly important among patients with HCC and a low TBS.

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ASO Visual Abstract: Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma-The Synergistic Impact of FIB-4 Index and Tumor Burden Score in Post-Hepatectomy Outcomes.

Akabane M, Kawashima J, Woldesenbet S, Macedo AB, Cauchy F, Shen F, Maithel SK, Koerkamp BG, Alexandrescu S, Kitago M, Weiss M, Martel G, Pulitano C, Aldrighetti L, Poultsides GA, Imaoka Y, Guglielmi A, Bauer TW, Endo I, Gleisner A, Marques HP, Pawlik TM

Annals of surgical oncology 32 （ 2 ） 1112 - 1113 2025年02月

ISSN  1068-9265

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Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma: The Synergistic Impact of the FIB-4 Index and Tumor Burden Score on Post-hepatectomy Outcomes.

Akabane M, Kawashima J, Woldesenbet S, Macedo AB, Cauchy F, Shen F, Maithel SK, Groot Koerkamp B, Alexandrescu S, Kitago M, Weiss M, Martel G, Pulitano C, Aldrighetti L, Poultsides GA, Imaoka Y, Guglielmi A, Bauer TW, Endo I, Gleisner A, Marques HP, Pawlik TM

Annals of surgical oncology 32 （ 2 ） 1011 - 1020 2025年02月

ISSN  1068-9265

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Background: The prognostic role of the fibrosis-4 (FIB-4) index relative to intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study sought to characterize the impact of the FIB-4 index and tumor burden score (TBS) on recurrence and overall survival (OS). Methods: ICC patients undergoing hepatectomy (2000–2020) were identified using a multi-institutional database. Patients were categorized as low (low TBS/low FIB-4 index), intermediate (low TBS/high FIB-4 index or high TBS/low FIB-4 index), and high (high TBS/high FIB-4 index). Results: Among 1168 patients in different TBS and FIB-4 index cohorts, 3-year recurrence varied considerably. For instance, among the patients with low TBS, individuals with a high FIB-4 index had a greater risk of recurrence than patients with a low FIB-4 index (59.9 vs. 47.7%; P = 0.01). Among patients with a high TBS, individuals with a high versus a low FIB-4 index had a higher incidence of recurrence (76.8 vs. 69.0%; P = 0.04). A similar pattern was observed among patients with both a low FIB-4 index (low [47.7%] vs. high [69.0%] TBS) and a high FIB-4 index (low [59.9%] vs. high [76.8%] TBS; both P < 0.001). Patients with a high [27.5%] versus a low [48.8%] TBS; P < 0.001) and patients with a high [34.2%] versus a low [43.5%] FIB-4 index; P = 0.01) had a worse OS. The multivariable analysis demonstrated an increasing risk of recurrence in the intermediate-index (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.20–2.16; P = 0.001) and high-index (HR, 2.13; 95% CI 1.45–3.13; P < 0.001) groups versus the low-index group. Conclusions: Both tumor-related and non-tumorous characteristics should be used to predict risk of recurrence and survival more accurately among patients with ICC following hepatic resection.

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