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- The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma.Publication . Kawashima, Jun; Endo, Yutaka; Woldesenbet, Selamawit; Khalil, Mujtaba; Akabane, Miho; Cauchy, François; Shen, Feng; Maithel, Shishir; Popescu, Irinel; Kitago, Minoru; Weiss, Matthew J; Martel, Guillaume; Pulitano, Carlo; Aldrighetti, Luca; Poultsides, George; Ruzzente, Andrea; Bauer, Todd W; Gleisner, Ana; Pinto Marques, Hugo; Groot Koerkamp, Bas; Endo, Itaru; Pawlik, Timothy MIntroduction: 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.
- Enhancing Recurrence-Free Survival Prediction in Hepatocellular Carcinoma: A Time-Updated Model Incorporating Tumor Burden and AFP Dynamics.Publication . Akabane, Miho; Kawashima, Jun; Altaf, Abdullah; Woldesenbet, Selamawit; Cauchy, François; Aucejo, Federico; Popescu, Irinel; Kitago, Minoru; Martel, Guillaume; Ratti, Francesca; Aldrighetti, Luca; Poultsides, George A; Imaoka, Yuki; Ruzzenente, Andrea; Endo, Itaru; Gleisner, Ana; Pinto Marques, Hugo; Oliveira, Sara; Balaia, Jorge; Lam, Vincent; Hugh, Tom; Bhimani, Nazim; Shen, Feng; Pawlik, Timothy MBackground: Existing models to predict recurrence-free survival (RFS) after hepatectomy for hepatocellular carcinoma (HCC) rely on static preoperative factors such as alpha-fetoprotein (AFP) and tumor burden score (TBS). These models overlook dynamic postoperative AFP changes, which may reflect evolving recurrence risk. We sought to develop a dynamic, real-time model integrating time-updated AFP values with TBS for improved recurrence prediction. Patients and methods: Patients undergoing curative-intent hepatectomy for HCC (2000-2023) were identified from an international, multi-institutional database with RFS as the primary outcome. AFP trajectory was monitored from preoperative to 6- and 12-month postoperative values, using time-varying Cox regression with AFP as a time-dependent covariate. The predictive accuracy of this time-updated model was compared with a static preoperative Cox model excluding postoperative AFP. Results: Among 1911 patients, AFP trajectories differed between recurrent and nonrecurrent cases. While preoperative AFP values were similar, recurrent cases exhibited higher AFP at 6 and 12 months. Multivariable analysis identified TBS (hazard ratio (HR):1.043 [95% confidence interval (CI): 1.002-1.086]; p = 0.039) and postoperative log AFP dynamics (HR:1.216 [CI 1.132-1.305]; p < 0.001) as predictors. Contour plots depicted TBS's influence decreasing over time, while postoperative AFP became more predictive. The time-varying Cox model was created to update RFS predictions continuously on the basis of the latest AFP values. The preoperative Cox model, developed with age, AFP, TBS, and albumin-bilirubin score, had a baseline C-index of 0.61 [0.59-0.63]. At 6 months, the time-varying model's C-index was 0.70 [0.67-0.73] versus 0.59 [0.56-0.61] for the static model; at 12 months, it was 0.70 [0.66-0.73] versus 0.56 [0.53-0.59]. The model was made available online ( https://nm49jf-miho-akabane.shinyapps.io/AFPHCC/ ). Conclusions: Incorporating postoperative AFP dynamics into RFS prediction after HCC resection enhanced prediction accuracy over time, as TBS's influence decreased. This adaptive, time-varying model provides refined RFS predictions throughout follow-up.
- Impact of Anatomical Resection on Non-transplantable Recurrence Among Patients with Hepatocellular Carcinoma: An International Multicenter Inverse Probability of Treatment Weighting Analysis.Publication . Kawashima, Jun; Endo, Yutaka; Khalil, Mujtaba; Woldesenbet, Selamawit; Akabane, Miho; Ruzzenente, Andrea; Ratti, Francesca; Marques, Hugo; Oliveira, Sara; Balaia, Jorge; Cauchy, François; Lam, Vincent; Poultsides, George; Kitago, Minoru; Popescu, Irinel; Martel, Guillaume; Gleisner, Ana; Hugh, Thomas J; Aldrighetti, Luca; Endo, Itaru; Pawlik, Timothy MBackground: Among patients with hepatocellular carcinoma (HCC), the impact of anatomic resection (AR) versus non-anatomic resection (NAR) on non-transplantable recurrence (NTR) remains poorly defined. We sought to compare the risk of NTR among patients treated with AR versus NAR as the primary surgical strategy for HCC. Patients and methods: Patients with HCC within Milan criteria who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. The inverse probability of treatment weighting (IPTW) method was utilized to compare short- and long-term outcomes among patients undergoing AR versus NAR. Results: Among 1038 patients, 747 (72.0%) patients underwent AR, while 291 (28.0%) patients underwent NAR. After IPTW adjustment, patients who underwent AR had better 5-year recurrence-free survival than individuals treated with NAR (63.9 vs. 52.0%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.62-0.99); however, there was no difference in 5-year overall survival (80.2 vs. 75.6%; HR 0.76; 95% CI 0.55-1.05). Notably, individuals who underwent AR were less likely to have a NTR versus individuals treated with NAR (3-year NTR 9.8 vs. 14.4%; HR 0.62; 95% CI 0.40-0.96). In particular, AR was associated with a lower risk of NTR among patients with a medium tumor burden score (TBS) (HR 0.53; 95% CI 0.28-0.99), while the benefit among patients with a low TBS was less pronounced (HR 0.73; 95% CI 0.40-1.32). Conclusions: AR was associated with a lower risk of NTR and improved recurrence-free survival (RFS) among patients with HCC, especially individuals with higher TBS. An anatomically defined surgical approach should be strongly considered in patients with a higher HCC tumor burden.
- A Comprehensive Preoperative Predictive Score for Post-Hepatectomy Liver Failure After Hepatocellular Carcinoma Resection Based on Patient Comorbidities, Tumor Burden, and Liver Function: the CTF Score.Publication . Alaimo, Laura; Endo, Yutaka; Lima, Henrique A; Moazzam, Zorays; Shaikh, Chanza Fahim; Ruzzenente, Andrea; Guglielmi, Alfredo; Ratti, Francesca; Aldrighetti, Luca; Pinto Marques, Hugo; Cauchy, François; Lam, Vincent; Poultsides, George A; Popescu, Irinel; Alexandrescu, Sorin; Martel, Guillaume; Hugh, Tom; Endo, Itaru; Pawlik, Timothy MBackground: Post-hepatectomy liver failure (PHLF) is a dreaded complication following liver resection for hepatocellular carcinoma (HCC) with a high mortality rate. We sought to develop a score based on preoperative factors to predict PHLF. Methods: Patients who underwent resection for HCC between 2000 and 2020 were identified from an international multi-institutional database. Factors associated with PHLF were identified and used to develop a preoperative comorbidity-tumor burden-liver function (CTF) predictive score. Results: Among 1785 patients, 106 (5.9%) experienced PHLF. On multivariate analysis, several factors were associated with PHLF including high Charlson comorbidity index (CCI ≥ 5) (OR 2.80, 95%CI, 1.08-7.26), albumin-bilirubin (ALBI) (OR 1.99, 95%CI, 1.10-3.56), and tumor burden score (TBS) (OR 1.06, 95%CI, 1.02-1.11) (all p < 0.05). Using the beta-coefficients of these variables, a weighted predictive score was developed and made available online ( https://alaimolaura.shinyapps.io/PHLFriskCalculator/ ). The CTF score (c-index = 0.67) performed better than Child-Pugh score (CPS) (c-index = 0.53) or Barcelona clinic liver cancer system (BCLC) (c-index = 0.57) to predict PHLF. A high CTF score was also an independent adverse prognostic factor for survival (HR 1.61, 95%CI, 1.12-2.30) and recurrence (HR 1.36, 95%CI, 1.08-1.71) (both p = 0.01). Conclusion: Roughly 1 in 20 patients experienced PHLF following resection of HCC. Patient (i.e., CCI), tumor (i.e., TBS), and liver function (i.e., ALBI) factors were associated with risk of PHLF. These preoperative factors were incorporated into a novel CTF tool that was made available online, which outperformed other previously proposed tools.
- Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, or One Anastomosis Gastric Bypass As Rescue Therapy After Failed Adjustable Gastric Banding: a Multicenter Comparative Study.Publication . Pujol Rafols, Juan; Al Abbas, Amr I; Devriendt, Stefanie; Guerra, Anabela; Herrera, Miguel F; Himpens, Jacques; Pardina, Eva; Peinado-Onsurbe, Julia; Ramos, Almino; Ribeiro, Rui José da Silva; Safadi, Bassem; Sanchez-Aguilar, Hugo; de Vries, Claire; Van Wagensveld, BartBackground: To date, laparoscopic adjustable gastric banding remains the third most commonly performed surgical procedure for weight loss. Some patients fail to get acceptable outcomes and undergo revisional surgery at rates ranging from 7% to 60%. Roux-en-Y gastric bypass (RYGB), one anastomosis gastric bypass (OAGB), and sleeve gastrectomy (SG) are among the most common salvage options for failed laparoscopic adjustable gastric banding. Objective: To compare the outcomes of converting failed laparoscopic adjustable gastric banding to RYGB, OAGB, or SG. Methods: Data collected from 7 experienced bariatric centers around the world were retrospectively collected, reviewed, and analyzed. Final body mass index (BMI), change in BMI, percentage excess BMI loss, and major complications with particular attention to leaks, hemorrhage, and mortality were reported. Results: Of 1219 patients analyzed, 74% underwent RYGB, 16% underwent OAGB, and 10% underwent SG after banding failure. The mean age was 38 years (±10 yr), and 82% of patients were women. The mean follow-up was 33 months. The follow-up rate was 100%, 87%, and 52% at 1, 3, and 5 years, respectively. At the latest follow-up, percentage excess BMI loss >50% was achieved by 75% of RYGB, 85% of OAGB, and 67% of SG patients. Postoperative complications occurred in 13% of patients after RYGB, 5% after OAGB, and 15% after SG. Conclusion: Our data show that it is possible to achieve or maintain significant weight loss with an acceptable complication rate with all 3 surgical options.
- Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma?Publication . Zhang, Xu-Feng; Lv, Yi; Weiss, Matthew; Popescu, Irinel; Pinto Marques, Hugo; Aldrighetti, Luca; Maithel, Shishir K; Pulitano, Carlo; Bauer, Todd W; Shen, Feng; Poultsides, George A; Soubrane, Oliver; Martel, Guillaume; Koerkamp, B Groot; Itaru, Endo; Pawlik, Timothy MObjective: We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC). Methods: Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report. Results: Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF + PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p < 0.001). Among the 129 patients with PI/MF + PI ICC subtype and preoperative nodal information, 72 (55.8%) were node-negative on preoperative imaging. In contrast, 57 (44.2%) patients had suspicious/metastatic LNs. On final pathologic examination, 45.3% (n = 24) of patients believed to be node-negative on preoperative imaging had LNM; 68.0% (n = 34) of patients who had suspicious/positive nodal disease on imaging ultimately had LNM (OR 2.6, p = 0.009). Conclusion: Given the low accuracy of preoperative imaging evaluation of nodal status, routine LND should be performed at the time of resection for both MF/IG and PI/MF + PI ICC subtypes.
- A Giant Arteriovenous Malformation of the Abdominal WallPublication . Figueiredo, Adriana; Gueifão, Inês; Fidalgo, Helena; Tavares, Carolina; Amaral, Carlos; Ferreira, Rita; Borges, Nuno; Ferreira, Maria EmiliaINTRODUCTION: Arteriovenous Malformations (AVMs) are high-fow anomalous connections between the arterial and venous systems composed of dysplastic vessels resulting from aberrant angiogenesis. They are congenital and when symptomatic they rarely manifest before adolescence. Depending on the location, size, stage and severity of the symptoms, treatment options vary from conservative management to surgical resection. We report a case of a giant arteriovenous malformation of abdominal wall (tipe IIIb of Yakes Classifcation) treated with surgical resection after prior attempts of scleroembolization.. CLINICAL CASE: 54-year-old woman with known history of osteoarticular pathology and dyspepsia presented a mass on the left side of the abdominal wall with hard consistency, warm, slightly pulsating and tenderness to touch with several years of evolution. The mass showed infltration of the internal and external oblique muscles sparing the transverse muscle. Clinically she presented easy fatigue with efforts. Due to the risk of abdominal wall herniation after excision of the AVM, scleroembolization was considered frst-line treatment in this case. This strategy resulted in regression of the mass and symptoms improvement. Four years after the last intervention, the patient presented lesion growth, recurrence and worsening of symptoms with severe interference in the quality of life (QoL). After multidisciplinary discussion, she was proposed for complete resection of the AVM. She was frst submitted to scleroembolization with Onyx of identifed arterial afferents and sclerosis of the lesion nidus with 2% polidocanol. One month after she underwent successfully total resection of the AVM with the collaboration of General Surgery. CONCLUSION: No unifed agreement exists on the best treatment of these complex high fow lesions and it is diffcult to establish a comprehensive strategy given the pathology’s clinical variability, complex stratifcation and the risk of relapse. A case-by-case approach is needed in managing these types of lesions.
- Preoperative Risk Score (PreopScore) to Predict Overall Survival After Resection for Hepatocellular Carcinoma.Publication . Endo, Yutaka; Lima, Henrique A; Alaimo, Laura; Moazzam, Zorays; Brown, Zachary; Shaikh, Chanza F; Ratti, Francesca; Pinto Marques, Hugo; Soubrane, Olivier; Lam, Vincent; Poultsides, George A; Popescu, Irinel; Alexandrescu, Sorin; Martel, Guillaume; Workneh, Aklile; Guglielmi, Alfredo; Hugh, Tom; Aldrighetti, Luca; Shen, Feng; Endo, Itaru; Pawlik, Timothy M; ElsevierBackground: This study aimed to develop a holistic risk score incorporating preoperative tumor, liver, nutritional, and inflammatory markers to predict overall survival (OS) after hepatectomy for hepatocellular carcinoma (HCC). Methods: Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using an international multi-institutional database. Preoperative predictors associated with OS were selected and a prognostic risk score model (PreopScore) was developed and validated using cross-validation. Results: A total of 1676 patients were included. On multivariable analysis, preoperative parameters associated with OS included α-feto protein (hazard ratio [HR]1.17, 95%CI 1.03-1.34), neutrophil-to-lymphocyte ratio (HR2.62, 95%CI 1.30-5.30), albumin (HR0.49, 95%CI 0.34-0.70), gamma-glutamyl transpeptidase (HR1.00, 95%CI 1.00-1.00), as well as vascular involvement (HR3.52, 95%CI 2.10-5.89) and tumor burden score (medium, HR3.49, 95%CI 1.62-7.58; high, HR3.21, 95%CI 1.40-7.35) on preoperative imaging. A weighted PreopScore was devised and made available online (https://yutaka-endo.shinyapps.io/PrepoScore_Shiny/). Patients with a PreopScore 0-2, 2-3.5, and >3.5 had incrementally worse 5-year OS of 85.8%, 70.7%, and 52.4%, respectively (p < 0.001). The c-index of the test and validation cohort were 0.75 and 0.71, respectively. The PreopScore outperformed individual parameters and previous HCC staging systems. Discussion: The PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies.
- Albumin-Bilirubin Grade and Tumor Burden Score Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma After Hepatic Resection: a Multi-Institutional Analysis.Publication . Munir, Muhammad Musaab; Endo, Yutaka; Lima, Henrique A; Alaimo, Laura; Moazzam, Zorays; Shaikh, Chanza; Poultsides, George A; Guglielmi, Alfredo; Aldrighetti, Luca; Weiss, Matthew; Bauer, Todd W; Alexandrescu, Sorin; Kitago, Minoru; Maithel, Shishir K; Pinto Marques, Hugo; Martel, Guillaume; Pulitano, Carlo; Shen, Feng; Cauchy, François; Koerkamp, Bas Groot; Endo, Itaru; Pawlik, Timothy M; SpringerBackground: The prognostic role of tumor burden score (TBS) relative to albumin-bilirubin (ALBI) grade among patients undergoing curative-intent resection of ICC has not been examined. Methods: We identified patients who underwent curative-intent resection for ICC between 1990 and 2017 from a multi-institutional database. Multivariable analysis was performed to assess the effect of TBS relative to ALBI grade on both short- and long-term outcomes. Results: Among 724 patients, 360 (49.7%) patients had low TBS and low ALBI grade, 142 (19.6%) patients had low TBS and high ALBI grade, 138 (19.1%) patients had high TBS and low ALBI grade, and 84 patients (11.6%) had high TBS and high ALBI grade. Decreased tumor burden was associated with better long-term outcomes among patients with both low (5-year OS; low TBS vs. high TBS: 52.4% vs 21.4%; p < 0.001) and high ALBI grade (5-year OS; low TBS vs. high TBS: 40.7% vs 12.0%; p < 0.001). On multivariable analysis, higher ALBI grade was associated with greater odds of an extended hospital LOS (> 10 days) (OR 2.80, 95%CI 1.62-4.82; p < 0.001), perioperative transfusion (OR 2.04, 95%CI 1.25-3.36; p = 0.005), 90-day mortality (OR 2.56, 95%CI 1.12-5.81; p = 0.025), as well as a major complication (OR 1.99, 95%CI 1.13-3.49; p = 0.016) among patients with similar tumor burden. Of note, patients with high TBS and high ALBI grade had markedly worse overall survival compared with patients who had low TBS and low ALBI grade disease (HR 2.27; 95%CI 1.44-3.59; p < 0.001). Importantly, high TBS and high ALBI grade were strongly associated with both early recurrence (88.1%%) and 5-year risk of death (96.4%). Conclusion: Both TBS (i.e., tumor morphology) and ALBI grade (i.e., hepatic function reserve) were strong predictors of outcomes among patients undergoing ICC resection. There was an interplay between TBS and ALBI grade relative to patient prognosis after hepatic resection of ICC with high ALBI grade predicting worse outcomes among ICC patients with different TBS.
- Cirurgia Robótica em Patologia Colorretal: Análise dos Primeiros Três Anos de Atividade num Hospital do Serviço Nacional de Saúde em PortugalPublication . Carrola Gomes, D; Athayde Nemésio, R; Rodrigues, S; Penedo, J; Paixão, IIntrodução: A utilização da cirurgia minimamente invasiva no tratamento da patologia colorretal é hoje cientificamente aceite e o seu uso na prática clínica diária tem vindo a aumentar de forma sustentada. Diversos estudos indicam que a abordagem robótica pode trazer vantagens sobre a laparoscopia ‘convencional’, especialmente na cirurgia do reto. Este trabalho descreve e analisa os resultados dos primeiros três anos de cirurgia robótica na Unidade de Patologia Colorretal da Unidade Local de Saúde S. José. Métodos: Foram definidas as variáveis a analisar e construída uma base de dados prospetiva com os dados referentes aos doentes operados consecutivamente por três cirurgiões colorretais, acreditados internacionalmente na utilização do sistema Da Vinci Xi®, entre novembro de 2019 e outubro de 2022. A base de dados foi convertida numa versão anonimizada e foi sobre essa mesma que se procedeu à análise de dados. Foram analisados os dados de todos doentes operados nesse período. Resultados: Foram incluídos 80 doentes, 47 homens, mediana de idade de 70 anos e de IMC de 26 kg/m2. O score ASA era II em 53,7% e III em 41,3% dos doentes. Do total, 97,6% apresentavam doença maligna ou potencialmente maligna. Realizaram-se 34 colectomias proximais ao ângulo esplénico, 20 distais e 26 ressecções anteriores do reto. Houve ressecção síncrona de metástases hepáticas em dois casos. Foram analisados os resultados peri-operatórios a curto prazo e histopatológicos: duração (mediana): 300 minutos; perda hemática estimada (mediana): 50 mL; taxa de conversão: 2,5%; dias até retomar trânsito intestinal (mediana): três dias; dias de internamento (mediana): seis dias; taxa de complicações pós-operatórias: 20%, das quais 5% Clavien III e 0% Clavien IV/V; taxa de deiscência anastomótica: 2,5%; taxa de reintervenção: 2,5%; taxa de readmissão pós-alta: 1,3%; gânglios linfáticos ressecados (mediana): 20; taxa de ressecção R0: 100%; taxa de integridade mesorretal: 95,8% completo/quase completo. Conclusão: Os nossos resultados mostram que a introdução da cirurgia colorretal robótica no nosso centro foi segura e garantiu resultados clínicos a curto prazo e histopatológicos semelhantes ou favoráveis face aos descritos na literatura.