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1. Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer

Author: Giulia Turri, Simone Caligola, Stefano Ugel, Cristian Conti, Silvia Zenuni, Valeria Barresi, Andrea Ruzzenente, Giuseppe Lippi, Aldo Scarpa, Vincenzo Bronte, Alfredo Guglielmi, and Corrado Pedrazzani
Subjects: colorectal cancer, inflammatory markers, prognosis, diagnosis, leucocytes, inflammation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: IntroductionEmerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values.MethodsRetrospective analysis of patients who underwent surgery for CRC at our center (2005 – 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed.ResultsPre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery.ConclusionTo our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC.
Published: 2023
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2. Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort studyResearch in context

Author: Anita Balakrishnan, Petros Barmpounakis, Nikolaos Demiris, Asif Jah, Harry V.M. Spiers, Shibojit Talukder, Jack L. Martin, Paul Gibbs, Simon J.F. Harper, Emmanuel L. Huguet, Vasilis Kosmoliaptsis, Siong S. Liau, Raaj K. Praseedom, Bristi Basu, Xavier de Aretxabala, Javier Lendoire, Shishir Maithel, Alejandro Branes, Bodil Andersson, Alejandro Serrablo, Volkan Adsay, Tomoyuki Abe, Moh'd Abu Hilal, Maria del Mar Achalandabaso Boira, Mustapha Adham, Mohamed Adam, Maryam Ahmad, Bilal Al-Sarireh, Maite Albiol, Nassir Alhaboob, Adnan Alseidi, Houssem Ammar, Akshay Anand, Pantelis Antonakis, Veronica Araya, Stanley W. Ashley, Georgi Atanasov, Fabio Ausania, Ricardo Balestri, Abhirup Banerjee, Simon Banting, Giedrius Barauskas, Fabian Bartsch, Andrea Belli, Simona Beretta, Frederik Berrevoet, Gerardo Blanco Fernandez, Louisa Bolm, Mathieu Bonal, Emre Bozkurt, Andries E. Braat, Luke Bradshaw, Lyle Burdine, Matthew Byrne, Maria Caceres, Maria Jesus Castro Santiago, Benjamin Chan, Lynn Chong, Ahmet Çoker, Maria Conde Rodriguez, Daniel Croagh, Alyn Crutchley, Carmen Cutolo, Mathieu D'Hondt, Daniel D'Souza, Freek Daams, Raffaele Dalla Valle, José Davide, Mario de Bellis, Marieke de Boer, Celine de Meyere, Philip de Reuver, Matthew Dixon, Panagiotis Dorovinis, Gabriela Echeverría Bauer, Maria Eduarda, Hasan Eker, Joris Erdmann, Mert Erkan, Evangelos Felekouras, Emanuele Felli, Eduardo Fernandes, Eduardo Figueroa Rivera, Andras Fulop, Daniel Galun, Michael Gerhards, Poya Ghorbani, Fabio Giannone, Luis Gil, Emmanouil Giorgakis, Mario Giuffrida, Felice Giuliante, Ioannis Gkekas, Miguel Gomez Bravo, Bas Groot Koerkamp, Oscar Guevara, Alfredo Guglielmi, Aiste Gulla, Rahul Gupta, Amit Gupta, Marta Gutiérrez, Abu Bakar Hafeez Bhatti, Jeroen Hagendoorn, Zain Hajee, Abdul Rahman Hakeem, Hytham Hamid, Sayed Hassen, Stefan Heinrich, Ryota Higuchi, Daniel Hoffman, David Holroyd, Daniel Hughes, Arpad Ivanecz, Satheesh Iype, Isabel Jaen Torrejimeno, Shantanu Joglekar, Robert Jones, Klaus Kaczirek, Harsh Kanhere, Ambareen Kausar, Zhanyi Kee, Jessica Keilson, Jorg Kleef, Johannes Klose, Brett Knowles, Jun Kit Koong, Nagappan Kumar, Supreeth Kunnuru, Paleswan Joshi Lakhey, Andrea Laurenzi, Yeong Sing Lee, Felipe Leon, Voon Meng Leow, Jean-Baptiste Lequeu, Mickael Lesurtel, Elisabeth Lo, Stefan Löb, Elizabeth Lockie, Peter Lodge, Dolores López Garnica, Victor Lopez Lopez, Linda Lundgren, Nikolaos Machairas, Dhiresh Maharjan, Deep Malde, Guillaume Martel, Julie Martin, Michele Mazzola, Arianeb Mehrabi, Ricardo Memeo, Flavio Milana, George Molina, Leah Monette, Haluk Morgul, Dimitrios Moris, Antonios Morsi-Yeroyannis, Nicholas Mowbray, Francesk Mulita, Edoardo Maria Muttillo, Malith Nandasena, Pueya Rashid Nashidengo, Arash Nickkholgh, Colin Byron Noel, Masayuki Ohtsuka, Arturs Ozolins, Sanjay Pandanaboyana, Nikolaos Pararas, Alessandro Parente, June Peng, Arkaitz Perfecto Valero, Julie Perinel, Konstatinos Perivoliotis, Teresa Perra, Patrick Pessaux, Natalie Petruch, Gaetano Piccolo, Laszlo Piros, Alberto Porcu, Viswakumar Prabakaran, Raj Prasad, Mikel Prieto Calvo, Florian Primavesi, Eva Maria Pueyo Periz, Alberto Quaglia, Jose M. Ramia Angel, Ashwin Rammohan, Francisco Razionale, Ricardo Robles Campos, Manas Roy, Sophie Rozwadowski, Luis Ruffolo, Natalia Ruiz, Andrea Ruzzenante, Lily Saadat, Mohamed Amine Said, Edoardo Saladino, Gabriel Saliba, Per Sandstrom, Carlo Alberto Schena, Anthony Scholer, Cristoph Schwartz, Lorenzo Serafini, Pablo Serrano, Deepak Sharma, Aali Sheen, Vishwanath Siddagangaiah, Michael Silva, Saurabh Singh, Ajith Siriwardena, Michal Skalski, Mante Smig, Faris Soliman, Donzília Sousa Silva, Ernesto Sparrelid, Parthi Srinivasan, Malin Sternby Eilard, Oliver Strobel, Urban Stupan, Miguel Angel Suarez-Munoz, Manisekar Subramaniam, Teiichi Sugiura, Robert Sutcliffe, Hilko Swank, Lillian Taylor, Prabin Bikram Thapa, Catherine The, Asara Thepbunchonchai, Caman Thieu, Navneet Tiwari, Guido Torzilli, Chutwichai Tovikkai, Blaz Trotovsek, Savvas Tsaramanidis, Georgios Tsoulfas, Katsuhiko Uesaka, Garzali Umar, Lucio Urbani, Michail Vailas, Ronald van Dam, Peter van de Boezem, Stijn van Laarhoven, Tomas Vanagas, Mike Van Dooren, Manon Viannet, Luca Vigano, Aarathi Vijayashanker, Celia Villodre, Toshifumi Wakai, Aklile Workneh, Li Xu, Masakazu Yamamoto, Zhiying Yang, Robert Young, and Marko Zivanovic
Subjects: Gallbladder cancer, Liver resection, Surgical outcomes, Cholangiocarcinoma, Medicine (General), R5-920
Abstract: Summary: Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p
Published: 2023
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3. Laparoscopic surgery does not reduce the need for red blood cell transfusion after resection for colorectal tumour: a propensity score match study on 728 patients

Author: Giulia Turri, Giovanni Malerba, Gabriele Gecchele, Cristian Conti, Federica Randon, Pierluigi Piccoli, Giorgio Gandini, Domenico Girelli, Alfredo Guglielmi, and Corrado Pedrazzani
Subjects: Colorectal surgery, Laparoscopy, Blood loss, Red blood cells transfusion, Surgery, RD1-811
Abstract: Abstract Background Patients with colorectal tumour often present with anaemia, and up to 60% will receive red blood cells (RBC) transfusion. Some evidence suggests a correlation between RBC transfusion and worse outcomes. Since laparoscopy minimizes intraoperative blood loss, we retrospectively investigated its role in reducing haemoglobin (Hb) drop and requirements for postoperative RBC transfusions. Methods Patients were identified from consecutive cases undergone elective surgery for non-metastatic colorectal tumour between 2005 and 2019. Laparoscopic cases were matched 1:1 with open controls through propensity score matching (PSM). The main outcome measures were postoperative Hb drop and requirement for RBC. The secondary aim was evaluation of risk factors for postoperative RBC transfusions. Results After application of PSM, 364 patients treated by laparoscopy were matched with 364 patients undergone open surgery. The two groups presented similar clinical and pathological characteristics, as well as comparable postoperative outcomes. 56 patients in the open group and 47 in the laparoscopic group required postoperative RBC (P = 0.395). No difference was observed in terms of mean number of RBC units (P = 0.608) or Hb drop (P = 0.129). Logistic regression analysis identified preoperative anaemia and occurrence of postoperative complications as relevant risk factors for postoperative RBC transfusion, while surgical approach did not prove statistically significant. Conclusion Laparoscopy did not influence postoperative requirements for RBC transfusions after elective colorectal surgery. Preoperative anaemia and occurrence of postoperative complications represent the major determinants for postoperative transfusions after open as well as laparoscopic surgery.
Published: 2022
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4. Endoscopic Ultrasound Through-the-Needle Biopsy for the Diagnosis of an Abdominal Bronchogenic Cyst

Author: Jessica Cassiani, Stefano Francesco Crinò, Erminia Manfrin, Matteo Rivelli, Armando Gabbrielli, Alfredo Guglielmi, and Corrado Pedrazzani
Subjects: bronchogenic cyst, endoscopic ultrasound-guided fine-needle aspiration, endoscopic ultrasound-guided through-the-needle biopsy, laparoscopy, pancreatic cyst, Internal medicine, RC31-1245, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: A 57-year-old woman with epigastric pain was diagnosed with a 6-cm abdominal cystic lesion of unclear origin on cross-sectional imaging. Endoscopic ultrasound (EUS) demonstrated a unilocular cyst located between the pancreas, gastric wall, and left adrenal gland, with a regular wall filled with dense fluid with multiple hyperechoic floating spots. A 19-G needle was used to puncture the cyst, but no fluid could be aspirated. Therefore, EUS-guided through-the-needle biopsy (EUS-TTNB) was performed. Histological analysis of the retrieved fragments revealed a fibrous wall lined by “respiratory-type” epithelium with ciliated columnar cells, consistent with the diagnosis of a bronchogenic cyst. Laparoscopic excision was performed, and the diagnosis was confirmed based on the findings of the surgical specimen. Abdominal bronchogenic cysts are extremely uncommon, and a definitive diagnosis is commonly obtained after the examination of surgical specimens due to the lack of pathognomonic findings on cross-sectional imaging and poor cellularity on EUS-guided fine-needle aspiration cytology. EUS-TTNB is useful for establishing a preoperative histological diagnosis, thus supporting the decision-making process.
Published: 2021
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5. Impact of age and comorbidities on short- and long-term outcomes of patients undergoing surgery for colorectal cancer

Author: Giulia Turri, Gulser Caliskan, Cristian Conti, Luigi Martinelli, Ernesto De Giulio, Andrea Ruzzenente, Alfredo Guglielmi, Giuseppe Verlato, and Corrado Pedrazzani
Subjects: elderly patients, colorectal cancer surgery, survival, comorbidities, mortality, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: BackgroundAs the world population is progressively ageing, more and more elderly patients will require cancer surgery. Although curative surgery is the treatment of choice for resectable colorectal cancer (CRC), it is still debated whether elderly frail patients should undergo major cancer surgery due to the increased risk of postoperative and long-term mortality. The aim of this retrospective study was to evaluate the impact of age and comorbidities on postoperative mortality/morbidity and long-term outcomes, looking for potential age-related survival differences.MethodsA total of 1,482 patients operated for CRC at our institution between January 2005 and October 2020 were analysed. The independent effect of age and comorbidities on postoperative complications was assessed by a logistic model, while the effect on overall survival (OS) and cancer-related survival (CRS) was estimated by a Cox regression model.ResultsThe median age in the cohort was 67.8 years. Postoperative mortality was very low in the whole cohort (0.8%) and contained even in older age groups (3.2% in patients aged 80–84 years, 4% in the 85–90-year age group). The cumulative incidence of postoperative complications was doubled in patients with comorbidities (32.8% vs. 15.1%, p = 0.002). With regard to OS, as expected, it exponentially decreased with advancing age. Conversely, differences in CRS were less pronounced between age groups and absent in patients with stage 0–I CRC. Analysis of all causes and cancer-related mortality revealed a peak within 2 years from surgery, suggesting a prolonged impact of surgery. In patients aged 75 years and above, all-cause mortality showed a steep increase 1 year after surgery, while cancer-related mortality plateaued at about 4 years after surgery. On multivariable analysis, OS, but not CRS, was significantly influenced by age.ConclusionsAlthough acceptable results of surgery in elderly patients, OS is strongly dependent on age: older people die more from competing causes than cancer-related treatments compared to younger age classes. The preoperative identification of risk factors for low OS may help the selection of those elderly patients who would benefit from curative CRC surgery.
Published: 2022
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6. Comparison of Short-term Results after Laparoscopic Complete Mesocolic Excision and Standard Colectomy for Right-Sided Colon Cancer: Analysis of a Western Center Cohort

Author: Cristian Conti, Corrado Pedrazzani, Giulia Turri, Eduardo Fernandes, Enrico Lazzarini, Raffaele De Luca, Alessandro Valdegamberi, Andrea Ruzzenente, and Alfredo Guglielmi
Subjects: laparoscopy, right hemicolectomy, colonic neoplasms, complete mesocolic excision, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Purpose Laparoscopic complete mesocolic excision (CME) right colectomy is a technically demanding procedure infrequently employed in Western centers. This retrospective cohort study aims to analyze the safety of laparoscopic CME colectomy compared to standard colectomy for right-sided colon cancer in a Western series. Methods Prospectively collected data from 60 patients who underwent laparoscopic CME right colectomy were compared to the ones of 55 patients who underwent laparoscopic standard right colectomy. Results No differences in clinical characteristics were observed between the CME and standard right colectomy groups. No differences were demonstrated in terms of blood loss (P = 0.060), intraoperative complications (P = 1), conversion rate (P = 0.102), and operative time (P = 0.473). No deaths were observed in either group, while complication rate was 40.0% in the CME and 49.1% in the standard group (P = 0.353). Severe complications occurred in 10.0% vs. 9.1% (P = 0.842), redo surgery in 5.0% vs. 7.3% (P = 0.708), and unplanned readmission in 5.0% vs. 5.5% (P = 1) after CME and standard colectomy, respectively. A significant difference in favor of CME was observed in the total length of specimen (P < 0.001), proximal (P = 0.018), and distal margins (P = 0.037). The number of lymph nodes harvested was significantly higher in the CME group (27 vs. 22, P = 0.037). Conclusion In Western series, where patients have less favorable clinical characteristics, laparoscopic CME allows to obtain better quality surgical specimens and comparable short-term outcomes compared to standard right colectomy.
Published: 2021
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7. Video technical notes for approaching a unique case of Juvenile Polyposis with massive gastric ingrowth

Author: Corrado Pedrazzani, Cristian Conti, Angelo Di Vittori, Giulia Turri, Laura Bernardoni, Andrea Mafficini, Claudio Luchini, Armando Gabbrielli, Aldo Scarpa, and Alfredo Guglielmi
Subjects: Surgery, RD1-811
Published: 2023
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8. Analgesic efficacy of preemptive local wound infiltration plus laparoscopic-assisted transversus abdominis plane block versus wound infiltration in patients undergoing laparoscopic colorectal resection: study protocol for a randomized, multicenter, single-blind, noninferiority trial

Author: Corrado Pedrazzani, Soo Yeun Park, Giovanni Scotton, Jun Seok Park, Hye Jin Kim, Enrico Polati, Alfredo Guglielmi, and Gyu Seog Choi
Subjects: Colorectal surgery, Laparoscopy, Postoperative analgesia, TAP block, Wound infiltration, Medicine (General), R5-920
Abstract: Abstract Background Transversus abdominis plane (TAP) block and wound infiltration (WI) are common locoregional anesthesia techniques for pain management in patients undergoing colorectal laparoscopic surgery. Comparative data between these two practices are conflicting, and a clear benefit of TAP block over WI is still debated. The main purpose of this study is to determine the efficacy in pain control of WI compared with WI plus laparoscopic TAP block (L-TAP) in cases of laparoscopic colorectal resection. Secondary aims are to evaluate other short-term results directly related to pain management: the need for rescue analgesic drugs, the incidence of postoperative nausea and vomiting, the resumption of gut functions, and the length of hospital stay. Methods/design This is a prospective, randomized, controlled, two-arm, multicenter, single-blind study evaluating the efficacy of postoperative analgesic management of WI versus WI plus L-TAP in the context of laparoscopic colorectal surgery. Randomization is at the patient level, and participants are randomized 1:1 to receive either WI alone or WI plus L-TAP. Those eligible for inclusion were patients undergoing laparoscopic resection for colorectal tumor or diverticular disease at the Division of General and Hepatobiliary Surgery, Verona University, Verona, Italy, and at the Colorectal Cancer Center, Kyungpook National University, Daegu, Korea. Fifty-four patients are needed in each group to evidence a difference greater than 1 of 10 according to the numeric rating scale for pain assessment to establish that this difference would matter in practice. Discussion The demonstration of a noninferiority of WI compared with WI plus L-TAP block would call into question TAP block usefulness in the setting of laparoscopic colorectal surgery. Trial registration ClinicalTrials.gov, NCT03376048. Prospectively registered on 15 December 2017.
Published: 2019
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9. Trace Elements Status and Metallothioneins DNA Methylation Influence Human Hepatocellular Carcinoma Survival Rate

Author: Silvia Udali, Domenica De Santis, Filippo Mazzi, Sara Moruzzi, Andrea Ruzzenente, Annalisa Castagna, Patrizia Pattini, Greta Beschin, Antonia Franceschi, Alfredo Guglielmi, Nicola Martinelli, Francesca Pizzolo, Francesca Ambrosani, Oliviero Olivieri, Sang-Woon Choi, and Simonetta Friso
Subjects: copper, DNA methylation, epigenetics, hepatocellular carcinoma, MT1G, MT1H, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: BackgroundMechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.MethodsForty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. MT1G and MT1H gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.ResultsPatients with Cu serum concentration above the 80th percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60–18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P
Published: 2021
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10. Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study

Author: Sèbastien Gaujoux, Nebyou Seyoum, Ville Sallinen, Ari Leppäniemi, Andrea Belli, Clare Skerritt, Naomi Wright, Savva Pronin, Azmina Verjee, Thomas Pinkney, Neil Smart, Oliver Warren, Michele Sacco, Arnav Agarwal, Simon Paterson-Brown, David Evans, Philip Choi, Ashish Gupta, Jonathan Myers, Victor Kong, Michael Wilson, Ewen M Harrison, Mircea Beuran, Ionut Negoi, Zahra Jaffry, Leonardo Solaini, Thomas M Drake, Dmitri Nepogodiev, Adesoji O Ademuyiwa, Philip Alexander, Sara W Al-Saqqa, Sule Burger, Kathryn Chu, Dhruv Ghosh, Hosni Khairy Salem, Marie Carmela Lapitan, Ismail Lawani, Maria Lorena Aguilera, Mayaba Maimbo, Alex Makupe, Rachel Moore, Vanessa Msosa, Alphonse Zeta Mutabazi, Riinu Ots, Ahmad Uzair Qureshi, Sarah Rayne, Marie Dione Parreno-Sacdalan, Richard Spence, Stephen Tabiri, Richard Lilford, Dion Morton, Aneel Bhangu, Tom Abbott, Gehad Tawfik, Sebastian King, Alexia Farrugia, Jay Park, Abhishek Sharma, Augusto Zani, Christopher Smith, Jonathan Lund, Stefano Giuliani, John Whitaker, Elaine Borg, Alexis Arnaud, Esther Ferrero, Andrea Ruzzenente, Jennifer Rickard, Yousef Abuowda, Enas Alaloul, Natalie Blencowe, Sanjay Patel, Mark Ian Hampton, Ewen Griffiths, André L Mihaljevic, Elizabeth Evans, Catherine A Shaw, Jennifer Ploski, Mengistu Worku, Ashish Minocha, Shiva Dindyal, Midhun Mohan, Dina Fouad, Christopher Owen, Priya Patel, Sunil Kumar, James Yang, Kevin C Conlon, Sandro Pasquali, Mohamed Mostafa, Yoshan Moodley, Kathryn Lee, James Glasbey, Gareth Irwin, Kjetil Søreide, Catrin Morgan, Ruth Blanco-Colino, Francesco Pata, Gianluca Pellino, Sivesh K Kamarajah, Luke Nicholson, Adesoji Ademuyiwa, Felix Alakaloko, Olumide Elebute, Omolara Faboya, Taiwo Lawal, Omolara Williams, Andrey Litvin, Elodie Haraux, James Olivier, Michael Stoddart, Rebecca White, George Ihediwa, Luigi Bonavina, Chetan Khatri, Stephen O'Neill, Roger Schmid, Stephen Knight, Ahmed Soliman, Carly Bisset, Robert Parker, Rakan Kabariti, Joshua Luck, Guo Liang Yong, Tanzeela Gala, David Bunting, Lydia Longstaff, Ye Ru Chin, J Edward Fitzgerald, Giuliano Borda-Luque, Ainhoa Costas-Chavarri, Faustin Ntirenganya, Stuart J Fergusson, JC Allen Ingabire, Lawani Ismaïl, Anyomih Theophilus Teddy Kojo, Adewale O Adisa, Tomas Poškus, Antonio Ramos-De la Medina, Sebastian Shu, Emmy Runigamugabo, Afnan Altamini, Andrew Kirby, Gustavo Recinos, Jen Cornick, Maria Marta Modolo, Sayeda Nazmum Nahar, Ade Waterman, Ismail Lawini, Mohammed Firdouse, Tyler Rouse, Qinyang Liu, Juan Camilo Correa, Peep Talving, Dushyant Iyer, Tom Arthur, MariaLorena Aguilera, Basant Kumar, Radhian Amandito, Roy Quek, Luca Ansaloni, Ahmed Altibi, Donatas Venskutonis, Justas Zilinskas, YongYong Tew, Ramos-DelaMedina Antonio, Zineb Bent, Ibrahim Al-Slaibi, Haya Tahboub, Osaid H Alser, Diego Romani, Sebestian Shu, Piotr Major, Aurel Mironescu, Matei Bratu, Amar Kourdouli, Saint Kitts, Mohammed Ubaid Alsaggaf, Ahmad Gudal, Al Faifi Jubran, Sierra Leone, Sam Seisay, Bettina Lieske, Irene Ortega, Jenifa Jeyakumar, Kithsiri Senanayake, Omar Abdulbagi, Yucel Cengiz, Dmitri Raptis, Yuksel Altinel, Chia Kong, Ella Teasdale, Sukrit Suresh, Katherine Gash, Mark Scott, Ragavan Narayanan, Besmir Grizhja, Shpetim Ymeri, Gezim Galiqi, Roberto Klappenbach, Diego Antezana, Alvaro Enrique MendozaBeleño, Cecilia Costa, Belen Sanchez, Susan Aviles, Claudio Gabriel Fermani, Rubén Balmaceda, Santiago Villalobos, Juan Manuel Carmona, Daniel Hamill, Peter Deutschmann, Simone Sandler, Daniel Cox, Ram Nataraja, Claire Sharpin, Damir Ljuhar, Demi Gray, Morgan Haines, Dush Iyer, Nithya Niranjan, Scott D'Amours, Morvarid Ashtari, Helena Franco, Ashrarur Rahman Mitul, Sabbir Karim, Nowrin F Aman, Mahnuma Mahfuz Estee, Umme Salma, Joyeta Razzaque, Tasnia Hamidkanta, Sayeedaaktar Tori, Md Shadid Alamin, Swapnil Roy, Md Shadid Al Amin, Muhtarima Haque, Amreen Faruq, Farhana Iftekhar Margaret, Greg Padmore O'Shea, Ramesh Jonnalagadda, Aliaksandr Filatau, Dzmitry Paulouski, Maryna Shubianok, Tatsiana Shachykava, Dzianis Khokha, Vladimir Khokha, Fernande Djivoh, Francis Dossou, Djifid Morel Seto, Dansou Gaspard Gbessi, Bruno Noukpozounkou, Yacoubou Imorou Souaibou, Kpèmahouton René Keke, Fred Hodonou, Ernestyemalinstephane Ahounou, Thierry Alihonou, Max Dénakpo, Germain Ahlonsou, Alemayehu Ginbo Bedada, Carlos Nsengiyumva, Sandrine Kwizera, Venerand Barendegere, Simon Stock, Luai Jamal, Georges Azzie, Sameer Kushwaha, Tzu-Ling Chen, Chingwan Yip, Irene Montes, Felipe Zapata, Sebastian Sierra, Mohamed Youssef, Hossam Elfeki, Waleed Thabet, Aly Sanad, Ahmed Zaki, Noran Abdel-Hameed, Esraa Abd Elkhalek, Yehia Zakaria, Tarek Ezzat, Ali Abo ElDahab, Mohamed Kelany, Sara Arafa, OsamaMokhtar Mohamed Hassan, Nermin Mohamed Badwi, Ahmad Saber Sleem, Hussien Ahmed, Kholoud Abdelbadeai, Mohamed Abozed Abdullah, Muhammadamsyarauni Lokman, Suraya Bahar, Anan Radyabdelazeam, Abdelrahman Adelshone, Muhammad Bin Hasnan, Athirah Zulkifli, Siti NurAlia Kamarulzamil, Abdelaziz Elhendawy, Aliang Latif, Ahmad Bin Adnan, Shahadatul Shaharuddin, Aminah HanumHaji AbdulMajid, Mahmoud Amreia, Dina Al-Marakby, Mahmoud Salma, Mohamadjeffreybin Ismail, Elissa Rifhan MohdBasir, Citra Dewi MohdAli, Aya Yehia Ata, Maha Nasr, Asmaa Rezq, Ahmed Sheta, Sherif Tariq, Abdelkhalek Sallam, Abdelrhman KZ Darwish, Sohaila Elmihy, Shady El Hadry, Ahmed Farag, Haidar Hajah, Abdelaziz Seliem, Amro Aglan, Ahmed Zohair, Mahitab Essam, Omar Moussa, Esraa El-Gizawy, Mostafa Samy, Safia Ali, Esraa Elhalawany, Ahmed Ata, Mohamed Elhalawany, Mohamed Nashat, Samar Soliman, Alaa Elazab, Mostada Samy, Mohamed A Abdelaziz, Khaled Ibrahim, Ahmed mohamed Ibrahim, Ammar Gado, Usama Hantour, Esraa Alm Eldeen, Mohamed Reda loaloa, Arwa Abouzaid, Mostafa Ahmedbahaaeldin, Eman Hashad, Fathy Sroor, Doaa Gamil, Eman Mahmoudabdulhakeem, Mahmoud Zakaria, Fawzy Mohamed, Marwan Abubakr, Elsayed Ali, Hesham Magdy, Mennatallah Ramadan, Mohamed Abdelatymohamed, Salma Mansour, Hager Abdulazizamin, Ahmed Rabiemohamed, Mahmoud Saami, Nada Ahmedredaelsayed, Adham Tarek, Sabry Mohyeldeenmahmoud, Islam MagdyEl Sayed, Amira Reda, Martina Yusufshawky, Mohammed Mousasalem, Shahinaz Alaa El-Din, Noha Abdullah Soliman, Muhammed Talaat, Shahinaz Alaael-Dein AhmedAbdelmoenelhusseiny, Noha Abdullah, Mohammed Elshaar, Aya Abdelfatahibraheem, Hager Abdulaziz, Mohammed Kamal Ismail, Mona Hamdymadkor, Mohamed Abdelaty, Sara Mahmoudabdel Kader, Osama Mohamedsalah, Mahmoud Eldafrawy, Ahmed Zakieldeeb, Mostafa Mahmoudeid, Attia Attia, Khalid Salah El-Dien, Ayman Shwky, Mohamed Adel Badenjki, Abdelrahman Soliman, Samaa Mahmoud Al Attar, Farrag Sayed, Fahd Abdelsabour, Mohammed G Azizeldine, Muhammad Shawqi, Abdullah Hashim, Ahmed Aamer, Ahmed Mahmoud Abdel Raouf, Mahmoud Abdelshakour, Amal Ibrahim, Basma Mahmoud, Mohamed Ali Mahmoud, Mostafa Qenawy, Ahmed M Rashed, Ahmed Dahy, Marwa Sayed, Ahmed W Shamsedine, Bakeer Mohamed, Ahmad Hasan, Mahmoud M Saad, Khalil Abdulbassit, Nadia Khalidabdelatif, Nada Elzahed, Ahmed Elkashash, Sarah Hafez, 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Gilani, Ida Björklund, Sandra Ahlqvist, Anders Thorell, Fredrik Wogensen, Arestis Sokratous, Michaela Breistrand, Hildur Thorarinsdottir, Johanna Sigurdadottir, Maziar Nikberg, Abbas Chabok, Maria Hjertberg, Peter Elbe, Deborah Saraste, Wiktor Rutkowski, Louise Forlin, Karoliina Niska, Malin Sund, Dennis Oswald, Georgios Peros, Rafael Bluelle, Katharina Reinisch, Daniel Frey, Adrian Palma, Dimitriaristotle Raptis, Lucius Zumbühl, Markus Zuber, Gabriela Werder, Antonio Nocito, Alexandra Gerosa, Silke Mahanty, Lukas Werner Widmer, Julia Müller, Alissa Gübeli, Grzegorz Zuk, Osman Bilgin Gulcicek, Talar Vartanoglu, Emin Kose, Servet Rustu Karahan, Mehmet Can Aydin, Nuri Alper Sahbaz, Ilkay Halicioglu, Halil Alis, Ipek Sapci, Can Adıyaman, Ahmet Murat Pektaş, Turgut Bora Cengiz, Ilkan Tansoker, Vedatcan Işler, Muazzez Cevik, Deniz Mutlu, Volkan Ozben, Berk Baris Ozmen, Sefa Bayram, Sinem Yolcu, Berna Buse Kobal, Ömer Faruk Toto, Haluk Cem Çakaloğlu, Kagan Karabulut, Vahit Mutlu, Bahar Busra Ozkan, Saban Celik, Anil Semiz, Selim Bodur, Enisburak Gül, Busra Murutoglu, Reyyan Yildirim, Bahadir Emre Baki, Ekin Arslan, Mehmet Ulusahin, Ali Guner, Nathan Walker, Nikhita Shrimanker, Simon Cole, Ryan Breslin, Ravi Srinivasan, Mohamed Elshaer, Kristina Hunter, Ahmed Al-Bahrani, Ignatius Liew, Nora Grace Mairs, Alistair Rocke, Lachlan Dick, Mobeen Qureshi, Debkumar Chowdhury, Adrienne Ho, Tharindra Dissanayake, Athula Tennakoon, Wadah Ali, Shujing Jane Lim, Charlene Tan, Catrin Jones, Dima Nassif, Aia Mehdi, Nathan Post, Eliana Kalakouti, Enkhbat Dashnyam, Frederick Stourton, Ioannis Mykoniatis, Chelise Currow, Francisca Wong, Veeranna Shatkar, Suraj Kadiwar, Alexander Smedley, Rebecca Wakefield, Philip Herrod, James Blackwell, Fraser Cohen, Ashwath Bandi, Giles Bond-Smith, Theodore Pezas, Neda Farhangmehr, Tomas Urbonas, Miklos Perenyei, Philip Ireland, Kirk Bowling, Kenneth Keogh, Hyunjin Jeon, Muhammad Rafaih Iqbal, Shivun Khosla, Anna Jeffery, James Perera, Ahmad Aboelkassem Ibrahem, Tariq Alhammali, Yahya Salama, Shaun Oram, Thomas Kidd, Fraser Cullen, Seehui Chiu, Hannah Sarafilovic, Athar Abbas, Sylvia Kamya, Norzawani Ishak, Cedar Andress, Aidan Haslegrave, Adam Boggon, Kirsten Laurie, Katie Connor, Thomas Mann, Anahita Mansuri, Rachel Davies, Aized Raza Shahbaz, Calvin Eng, Farhat Din, Ariadne L'heveder, Esther H.G. Park, Ramanish Ravishankar, Kirsten Mcintosh, Jih Dar Yau, Luke Chan, Susan Mcgarvie, Lingshan Tang, Hui Lim, Suhhuey Yap, Zhanherr Ng, Shahrukh Mirza, Yun Lin Ang, Luke Walls, Chloe Roy, Julian Camilleri-Brennan, Kenneth Mclean, Michelle D'souza, David Ewart Henshall, Eunicezuling Ter, William English, Dominic Townsend, Laura Maciejec, Shareef Mahdi, Onyinye Akpenyi, Elisabeth Hall, Hanaan Caydiid, Zakaria Rob, Hew D Torrance, Robin Johnston, Mohammedakil Gani, Gianpiero Gravante, Shivanchan Rajmohan, Kiran Majid, Madanmohan Palliyil, Neil Harvey, Katie Baillie, Sam Shillito, Suzanne Kershaw, Rebecca Bamford, Peter Orton, Elke Reunis, Robert Tyler, Waicheong Soon, Guled M. Jama, Dharminder Dhillon, Khyati Patel, Shayanthan Nanthakumaran, Rachel Heard, Kar Yan Chen, Behrad Barmayehvar, Uttaran Datta, Sobhana Iftekhartani, Eimear Monaghan, Philippa Donnelly, Michael Walker, Jehangirshaw Parakh, Sarah Blacker, Anil Kaul, Arjun Paramasivan, Sameh Farag, Ashrafun Nessa, Salwa Awadallah, Jieqi Lim, James Cheankhunng, Ravi P. Kiran, Alice Murray, Eric Etchill, Mohini Dasari, Juan Puyana, Nadeem Haddad, Martin Zielinski, Asad Choudhry, Celeste Caliman, Mieshia Beamon, Therese Duane, Mamta Swaroop, Rebecca Deal, Erik Schadde, Mark Hemmila, Lena Napolitano, Kathleen To, Joseph Musowoya, Niels Van Der Naald, Dayson Kumwenda, Alex Reece-Smith, Kars Otten, Anna Verbeek, Marloes Prins, Alibeth Andres Baquero Suarez, Chelsea Deane, Emilio Dijan, Mahmoud Elfiky, Laura Koskenvuo, Aurore Thollot, Bernard Limoges, Carmen Capito, Challine Alexandre, Henri Kotobi, Julien Leroux, Kalitha Pinnagoda, Nicolas Henric, Olivier Azzis, Olivier Rosello, Poddevin Francois, Sara Etienne, Philippe Buisson, Sophian Hmila, Joe-Nat Clegg-Lamptey, Osman Imoro, Owusu Emmanuel Abem, Dimitrios Papageorgiou, Vasiliki Soulou, Sabrina Asturias, Lenin Peña, Donal B O’Connor, Alberto Realis Luc, Alfio Alessandro Russo, Antonio Taddei, Camilla Cona, Corrado Bottini, Giovanni Pascale, Giuseppe Rotunno, Marco Maria Pascale, Margherita Notarnicola, Mario Corbellino, Paolo Ubiali, Roberto Cautiero, Tommaso Bocchetti, Elena Muzio, Vania Guglielmo, Eugenio Morandi, Patrizio Mao, Emilia De Luca, Farah Mahmoud Ali, Kestutis Strupas, Paulius Kondrotas, Robertas Baltrunas, Juozas Kutkevicius, Povilas Ignatavicius, Choy Ling Tan, Jia Yng Siaw, Sir Young Yam, Ling Wilson, Mohamed Rezal Abdul Aziz, John Bondin, Carmina Diaz Zorrilla, Anass Majbar, Danjuma Sale, Lawal Abdullahi, Olabisi Osagie, Adedeji Fatuga, Agboola Taiwo, Emeka Nwabuoku, Marte BliksØen, Zain Ali Khan, Jazmin Coronel, Cesar Miranda, Idelso Vasquez, Luis M. Helguero-Santin, Adesina Adedeji, Saleh Alqahtani, Max Rath, Michael Van Niekerk, Modise Zacharia Koto, Roel Matos-Puig, Leif Israelsson, Tobias Schuetz, Mahmut Arif Yuksek, Meric Mericliler, Bernhard Wolf, Cameron Fairfield, Katharine Whitehurst, Natalie Redgrave, Caroluce K Musyoka, Michael Cox, Muhamed M H Farhan-Alanie, Rory Callan, Chali Chibuye, Tebian Hassanein Ahmed Ali, Syrine Rekhis, Muna Rommaneh, Zi Hao Sam, Thays Brunelli Pugliesi, Gabriel Pardo, and Ruth Blanco
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).Results Of 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
Published: 2020
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11. Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

Author: Michele Simbolo, Caterina Vicentini, Andrea Ruzzenente, Matteo Brunelli, Simone Conci, Matteo Fassan, Andrea Mafficini, Borislav Rusev, Vincenzo Corbo, Paola Capelli, Emilio Bria, Serena Pedron, Giona Turri, Rita T. Lawlor, Giampaolo Tortora, Claudio Bassi, Alfredo Guglielmi, and Aldo Scarpa
Subjects: Medicine, Science
Abstract: Abstract The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive behaviour, two prognostic groups of patient were selected and divided according to prognostic performance. All patients alive at 36 months were included in good prognostic performers, while all patients died due to disease within 36 months in poor prognostic performers. Using high-coverage target sequencing we analysed principal genetic alterations in two groups and compared results to clinical data. In the 33 cases included in poor prognosis group, TP53 was most mutated gene (p = 0.011) and exclusively present in these cases. Similarly, ARID1A was exclusive of this group (p = 0.024). TP53 and ARID1A are mutually exclusive in this study. Statistical analysis showed mutations in TP53 and ARID1A genes and amplification of MET gene as independent predictors of poor prognosis (TP53, p = 0.0031, ARID1A, p = 0.0007, MET, p = 0.0003 in Cox analysis). LOH in PTEN was also identified as marker of disease recurrence (p = 0.04) in univariate analysis. This work improves our understanding of aggressiveness related to this tumour type and has identified novel prognostic markers of clinical outcome.
Published: 2018
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12. Assessment of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet count as predictors of long-term outcome after R0 resection for colorectal cancer

Author: Corrado Pedrazzani, Guido Mantovani, Eduardo Fernandes, Fabio Bagante, Gian Luca Salvagno, Niccolò Surci, Tommaso Campagnaro, Andrea Ruzzenente, Elisa Danese, Giuseppe Lippi, and Alfredo Guglielmi
Subjects: Medicine, Science
Abstract: Abstract Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet count (PC) were shown to be prognostic in several solid malignancies. We analysed 603 R0 resected patients to assess whether NLR, PLR and PC correlate with other well-known prognostic factors and survival of patients with colorectal cancer (CRC). Receiver operating characteristic (ROC) curve analysis was performed to define cut-off values for high and low ratios of these indices. Univariate and multivariate analysis were used to determine the prognostic value of NLR, PLR and PC for overall and cancer-related survival. The distribution of NLR, PLR and PC in CRC patients was compared with 5270 healthy blood donors. The distribution of NLR, PLR and PC was significantly different between CRC patients and controls (all p
Published: 2017
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13. Clinical Significance of Preoperative Inflammatory Markers in Prediction of Prognosis in Node-Negative Colon Cancer: Correlation between Neutrophil-to-Lymphocyte Ratio and Poorly Differentiated Clusters

Author: Giulia Turri, Valeria Barresi, Alessandro Valdegamberi, Gabriele Gecchele, Cristian Conti, Serena Ammendola, Alfredo Guglielmi, Aldo Scarpa, and Corrado Pedrazzani
Subjects: colon cancer, poorly differentiated clusters, prognostic factors, inflammatory markers, histopathological markers, immune system, Biology (General), QH301-705.5
Abstract: Although stage I and II colon cancers (CC) generally show a very good prognosis, a small proportion of these patients dies from recurrent disease. The identification of high-risk patients, who may benefit from adjuvant chemotherapy, becomes therefore essential. We retrospectively evaluated 107 cases of stage I (n = 28, 26.2%) and II (n = 79, 73.8%) CC for correlations among preoperative inflammatory markers, histopathological factors and long-term prognosis. A neutrophil-to-lymphocyte ratio greater than 3 (H-NLR) and a platelet-to-lymphocyte ratio greater than 150 (H-PLR) were significantly associated with the presence of poorly differentiated clusters (PDC) (p = 0.007 and p = 0.039, respectively). In addition, H-NLR and PDC proved to be significant and independent survival prognosticators for overall survival (OS; p = 0.007 and p < 0.001, respectively), while PDC was the only significant prognostic factor for cancer-specific survival (CSS; p < 0.001,). Finally, the combination of H-NLR and PDC allowed an optimal stratification of OS and CSS in our cohort, suggesting a potential role in clinical practice for the identification of high-risk patients with stage I and II CC.
Published: 2021
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14. DNA Methylation and Hydroxymethylation in Primary Colon Cancer and Synchronous Hepatic Metastasis

Author: Silvia Udali, Domenica De Santis, Andrea Ruzzenente, Sara Moruzzi, Filippo Mazzi, Greta Beschin, Stephanie A. Tammen, Tommaso Campagnaro, Patrizia Pattini, Oliviero Olivieri, Alfredo Guglielmi, Sang-Woon Choi, and Simonetta Friso
Subjects: epigenetics, methylcytosine, hydroxymethylcytosine, primary colon cancer, synchronous hepatic metastasis, Genetics, QH426-470
Abstract: Colon cancer is one of the most frequent solid tumor and simultaneous diagnosis of primary colon cancer and liver metastases occurs in about one fourth of cases. The current knowledge on epigenetic signatures, especially those related to hydroxymethylation in primary cancer tissue, synchronous metastasis, and blood circulating cells is lacking. This study aimed to investigate both methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) status in the DNA of individual patients from colon cancer tissue, synchronous liver metastases, and in cancer-free colon and liver tissues and leukocytes. Patients undergoing curative surgery (n = 16) were enrolled and their laboratory and clinical history data collected. The contents of mCyt and hmCyt were determined by a liquid chromatography/mass spectrometry (LC/MS/MS) method in DNA extracted from primary colon cancer, synchronous hepatic metastatic tissues and homologous cancer-free tissues, i.e., colon and liver tissues as well as leukocytes. The mCyt and hmCyt levels were compared between cancerous and cancer-free tissues, and correlations between leukocytes and colon/liver tissues for both the mCyt and hmCyt levels were evaluated. The mCyt levels were similar in primary colon cancer and liver metastasis tissues (4.69 ± 0.37% vs. 4.77 ± 0.38%, respectively, p = 0.535), and both primary and metastatic tissues were hypomethylated compared to cancer-free colon (4.98 ± 0.26%). The difference in the mCyt content between cancerous and cancer-free colon tissues was significantly lower in primary colon cancer (p = 0.004), but not in liver metastasis (p = 0.148). The hmCyt content was similar in primary colon cancer compared to liver metastasis (0.035%, C.I. 0.024–0.052% versus 0.035%, C.I. 0.021–0.058%, respectively, p = 0.905) and markedly depleted compared to the cancer-free colon (0.081%, C.I. 0.055–0.119%) with a statistically significant difference (p < 0.05) for both comparisons. The mCyt levels showed a borderline correlation between leukocytes and colon cancer tissue (Pearson’s correlation coefficient = 0.51, p = 0.052) while no correlations were detected for the hmCyt levels. In conclusion, primary colon cancer and synchronous liver metastasis tissues showed a similar epigenetic status but were significantly hypomethylated and hypohydroxymethylated as compared to homologous cancer-free colon tissues.
Published: 2018
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15. One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation.

Author: Sara Moruzzi, Patrizia Guarini, Silvia Udali, Andrea Ruzzenente, Alfredo Guglielmi, Simone Conci, Patrizia Pattini, Nicola Martinelli, Oliviero Olivieri, Stephanie A Tammen, Sang-Woon Choi, and Simonetta Friso
Subjects: Medicine, Science
Abstract: Several polymorphic gene variants within one-carbon metabolism, an essential pathway for nucleotide synthesis and methylation reactions, are related to cancer risk. An aberrant DNA methylation is a common feature in cancer but whether the link between one-carbon metabolism variants and cancer occurs through an altered DNA methylation is yet unclear. Aims of the study were to evaluate the frequency of one-carbon metabolism gene variants in hepatocellular-carcinoma, cholangiocarcinoma and colon cancer, and their relationship to cancer risk together with global DNA methylation status. Genotyping for BHMT 716A>G, DHFR 19bp ins/del, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, TCII 776C>G and TS 2rpt-3rpt was performed in 102 cancer patients and 363 cancer-free subjects. Methylcytosine (mCyt) content was measured by LC/MS/MS in peripheral blood mononuclear cells (PBMCs) DNA. The MTHFD1 1958AA genotype was significantly less frequent among cancer patients as compared to controls (p = 0.007) and related to 63% reduction of overall cancer risk (p = 0.003) and 75% of colon cancer risk (p = 0.006). When considering PBMCs mCyt content, carriers of the MTHFD1 1958GG genotype showed a lower DNA methylation as compared to carriers of the A allele (p = 0.048). No differences were highlighted by evaluating a possible relationship between the other polymorphisms analyzed with cancer risk and DNA methylation. The MTHFD1 1958AA genotype is linked to a significantly reduced cancer risk. The 1958GG genotype is associated to PBMCs DNA hypomethylation as compared to the A allele carriership that may exert a protective effect for cancer risk by preserving from DNA hypomethylation.
Published: 2017
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16. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers.

Author: Sara Moruzzi, Silvia Udali, Andrea Ruzzenente, Alfredo Guglielmi, Patrizia Guarini, Nicola Martinelli, Simone Conci, Filippo Mazzi, Patrizia Pattini, Stephanie A Tammen, Oliviero Olivieri, Francesca Pizzolo, Sang-Woon Choi, and Simonetta Friso
Subjects: Medicine, Science
Abstract: Polymorphisms within one-carbon metabolism genes have been largely studied in relation to cancer risk for the function of this pathway in nucleotide synthesis and DNA methylation. Aims of this study were to explore the possible link among several common functional gene polymorphisms within one-carbon metabolism and survival rate in primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma, and to assess the additional effect of global DNA methylation on survival rate and mortality risk. Forty-seven primary liver cancer patients were genotyped for ten polymorphisms: DHFR 19bp ins/del, TS 2rpt-3rpt, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, BHMT 716 A>G, TC II 776C>G. Methylation was determined in peripheral blood mononuclear cells (PBMCs) DNA as methylcytosine (mCyt) content using LC/MS/MS. Among the polymorphisms analysed, the RFC1 80G>A (rs1051266) influenced the survival rate in primary liver cancers. The RFC1 80AA was associated to a significantly reduced survival rate (22.2%) as compared to both GG and GA genotypes (61.5% and 76% respectively, p = 0.005). When the cancer patients were stratified according to the mCyt median value as high (>5.34%) or low (≤5.34%), the concomitant presence of AA genotype and low mCyt level led to a significantly worse survival rate as compared to the G allele carriership (pA polymorphism influenced the survival rate, and the presence of RFC1 80AA genotype with low global methylation in PBMCs DNA was associated with poorer prognosis and higher mortality risk, therefore highlighting novel molecular signatures potentially helpful to define prognostic markers for primary liver cancers.
Published: 2016
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17. A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of fishing c-myc gene for early relapse.

Author: Federica Pedica, Andrea Ruzzenente, Fabio Bagante, Paola Capelli, Ivana Cataldo, Serena Pedron, Calogero Iacono, Marco Chilosi, Aldo Scarpa, Matteo Brunelli, Anna Tomezzoli, Guido Martignoni, and Alfredo Guglielmi
Subjects: Medicine, Science
Abstract: Hepatocellular carcinoma is one leading cause of cancer-related death and surgical resection is still one of the major curative therapies. Recently, there has been a major effort to find mechanisms involved in carcinogenesis and early relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to analyze the role of c-myc as prognostic factor in terms of overall survival and disease-free survival and to investigate if c-myc may be an important target for therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical resection with curative intent. Size, macro-microvascular invasion, necrosis, number of nodules, grading and serum alfa-fetoprotein level were registered for all cases. We evaluated the c-myc aberrations by using break-apart FISH probes. Probes specific for the centromeric part of chromosome 8 and for the locus specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes (polysomy due to polyploidy) and amplification. c-myc gene amplification was scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and overall survival were performed. At molecular level, c-myc was amplified in 19% of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of cases. The 1- and 3-year disease-free survival and overall survival for disomic, polysomic and amplified groups were significantly different (p=0.020 and p=.018 respectively). Multivariate analysis verified that the AFP and c-myc status (amplified vs. not amplified) were significant prognostic factors for overall patients survival. c-myc gene amplification is significantly correlated with disease-free survival and overall survival in patients with hepatocellular carcinoma after surgical resection and this model identifies patients with risk of early relapse (≤12 months). We suggest that c-myc assessment may be introduced in the clinical practice for improving prognostication (high and low risk of relapse) routinely and may have be proposed as biomarker of efficacy to anti-c-myc targeted drugs in clinical trials.
Published: 2013
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18. The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma

Author: Laura Alaimo, Zorays Moazzam, Yutaka Endo, Henrique A. Lima, Swatika P. Butey, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Minoru Kitago, Alex Kim, Aslam Ejaz, Joal Beane, Jordan Cloyd, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery
Abstract: BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with poor long-term outcomes, and limited evidence exists on optimal resection margin width. This study used artificial intelligence to investigate long-term outcomes and optimal margin width in hepatectomy for ICC.METHODS: The study enrolled patients who underwent curative-intent resection for ICC between 1990 and 2020. The optimal survival tree (OST) was used to investigate overall (OS) and recurrence-free survival (RFS). An optimal policy tree (OPT) assigned treatment recommendations based on random forest (RF) counterfactual survival probabilities associated with each possible margin width between 0 and 20 mm.RESULTS: Among 600 patients, the median resection margin was 4 mm (interquartile range [IQR], 2-10). Overall, 379 (63.2 %) patients experienced recurrence with a 5-year RFS of 28.3 % and a 5-year OS of 38.7 %. The OST identified five subgroups of patients with different OS rates based on tumor size, a carbohydrate antigen 19-9 [CA19-9] level higher than 200 U/mL, nodal status, margin width, and age (area under the curve [AUC]: training, 0.81; testing, 0.69). The patients with tumors smaller than 4.8 cm and a margin width of 2.5 mm or greater had a relative increase in 5-year OS of 37 % compared with the entire cohort. The OST for RFS estimated a 46 % improvement in the 5-year RFS for the patients younger than 60 years who had small (CONCLUSIONS: Artificial intelligence OST identified subgroups within ICC relative to long-term outcomes. Although tumor biology dictated prognosis, the OPT suggested that different margin widths based on patient and disease characteristics may optimize ICC long-term survival.
Published: 2023

19. Higher Tumor Burden Status Dictates the Impact of Surgical Margin Status on Overall Survival in Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma

Author: Yutaka Endo, Kazunari Sasaki, Zorays Moazzam, Henrique A. Lima, Laura Alaimo, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Minoru Kitago, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery, Intrahepatic Cholangiocarcinoma, Surgical Margin Status, Tumor Burden, Surgical Margin Status, Intrahepatic Cholangiocarcinoma, Tumor Burden
Abstract: BACKGROUND: The present study aimed to examine the prognostic significance of margin status following hepatectomy of intrahepatic cholangiocarcinoma (ICC) relative to overall tumor burden and nodal status.METHOD: Patients who underwent curative-intent surgery for ICC between 1990 and 2017 were included from a multi-institutional database. The impact of margin status and width on overall survival (OS) was examined relative to TBS and preoperative nodal status.RESULTS: Among 1105 patients with ICC who underwent resection, median tumor burden score (TBS) was 6.1 (IQR 4.2-8.8) and 218 (19.7%) patients had N1 disease. More than one in eight patients had an R1 surgical margin (n = 154, 13.9%). Among patients with low or medium TBS, an increasing margin width was associated with an incrementally improved 5-year OS (R1 31.9% vs. 1-3 mm 38.5% vs. 3-10 mm 48.0% vs. ≥ 10 mm 52.3%). In contrast, among patients with a high TBS, margin width was not associated with better survival (R1 28.9% vs. 1-3 mm 22.8% vs. 3-10 mm 29.6% vs. ≥ 10 mm 13.7%). In addition, surgical margin status did not impact survival with cutoffs of TBS 7 or greater. Furthermore, patients with low or medium TBS and preoperative negative lymph nodes derived a survival benefit from an R0 resection (R1 resection, HR 2.15, 95% CI 1.35-3.44, p = 0.001). In contrast, margin status was not associated with prognosis among patients with a high TBS and preoperative positive/suspicious lymph nodes (R1 resection, HR 1.34, 95% CI 0.58-3.11, p = 0.50).CONCLUSION: R0 resection and wider margin resection resulted in improved outcomes in patients with low tumor burden; however, the survival benefit of negative margin status disappeared in patients with underlying poor tumor biology.
Published: 2023

20. Simultaneous versus staged resection for synchronous colorectal liver metastases: The win ratio approach

Author: Yutaka Endo, Laura Alaimo, Henrique Araujo Lima, Diamantis I. Tsilimigras, J. Madison Hyer, Alfredo Guglielmi, Andrea Ruzzenente, Sorin Alexandrescu, George Poultsides, Kazunari Sasaki, Federico Aucejo, and Timothy M. Pawlik
Subjects: Synchronous colorectal liver metastases, Win ratio, Hepatology, Simultaneous resection, Gastroenterology, Staged resection, Surgery, General Medicine, Multi-institutional study
Abstract: In order to investigate the optimal approach for synchronous colorectal liver metastases (sCRLM), we sought to use the "win ratio" (WR), a novel statistical approach, to assess the relative benefit of simultaneous versus staged surgical treatment.Patients who underwent hepatectomy for sCRLM between 2008 and 2020 were identified from a multi-institutional database. The WR approach was utilized to compare composite outcomes of patients undergoing simultaneous versus staged resection.Among 1116 patients, 642 (57.5%) presented with sCRLM; 290 (45.2%) underwent simultaneous resection, while 352 (54.8%) underwent staged resection. In assessing the composite outcome, staged resection yielded a WR of 1.59 (95%CI 1.47-1.71) over the simultaneous approach for sCRLM. The highest WR occurred among patients requiring major hepatectomy (WR = 1.93, 95%CI 1.77-2.10) compared with patients who required minor liver resection (WR = 1.55, 95%CI 1.44-1.70).Staged resection was superior to simultaneous resection for sCRLM based on a WR assessment.
Published: 2023

21. Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma

Author: Laura Alaimo, Zorays Moazzam, Yutaka Endo, Henrique A. Lima, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery
Abstract: INTRODUCTION: While generally associated with poor prognosis, intrahepatic cholangiocarcinoma (ICC) can have a heterogeneous presentation and natural history. We sought to identify specific ICC subtypes that may be associated with varied long-term outcomes and patterns of recurrence after liver resection.METHODS: Patients who underwent curative-intent resection for ICC from 2000 to 2020 were identified from a multi-institutional database. Hierarchical cluster analysis characterized three ICC subtypes based on morphology (i.e., tumor burden score [TBS]) and biology (i.e., preoperative neutrophil-to-lymphocyte ratio [NLR] and CA19-9 levels).RESULTS: Among 598 patients, the cluster analysis identified three ICC subtypes: Common (n = 300, 50.2%) (median, TBS: 4.5; NLR: 2.4; CA19-9: 38.0 U/mL); Proliferative (n = 246, 41.1%) (median, TBS: 8.8; NLR: 2.9; CA19-9: 71.2 U/mL); Inflammatory (n = 52, 8.7%) (median, TBS: 5.4; NLR: 12.6; CA19-9: 26.7 U/mL). Median overall survival (OS) (Common: 72.0 months; Proliferative: 31.4 months; Inflammatory: 22.9 months) and recurrence-free survival (RFS) (Common: 21.5 months; Proliferative: 11.9 months; Inflammatory: 9.0 months) varied considerably among the different ICC subtypes (all p CONCLUSIONS: Cluster analysis identified three distinct subtypes of ICC based on TBS, NLR, and CA19-9. ICC subtype was associated with RFS and OS and predicted worse outcomes among patients. Despite more favorable T- and N-disease, the Inflammatory ICC subtype was associated with worse outcomes ICC subtype should be considered in the prognostic stratification of patients.
Published: 2023

22. Telemedicine and Pancreatic Cancer: A Systematic Review

Author: Marzia Tripepi, Erica Pizzocaro, Alessandro Giardino, Isabella Frigerio, Alfredo Guglielmi, and Giovanni Butturini
Subjects: Health Information Management, telehealth, pancreatic cancer, telemonitoring, Health Informatics, telemedicine, General Medicine, teledischarge
Published: 2023

23. Simultaneous resection of colorectal cancer and synchronous liver metastases

Author: Jasper P. Sijberden, Giuseppe Zimmitti, Simone Conci, Nadia Russolillo, Michele Masetti, Federica Cipriani, Jacopo Lanari, Burak Görgec, Andrea Benedetti Cacciaguerra, Fernando Rotellar, Mathieu D’Hondt, Bjørn Edwin, Robert P. Sutcliffe, Ibrahim Dagher, Mikhail Efanov, Santi López-Ben, John N. Primrose, Felice Giuliante, Antonino Spinelli, Manish Chand, Salud Alvarez, Serena Langella, Simone Nicosia, Andrea Ruzzenente, Marco Vivarelli, Umberto Cillo, Luca Aldrighetti, Elio Jovine, Alessandro Ferrero, Alfredo Guglielmi, Marc G. Besselink, Mohammad Abu Hilal, Graduate School, Surgery, CCA - Cancer Treatment and Quality of Life, Radiology and Nuclear Medicine, CCA - Imaging and biomarkers, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Surgery, General Medicine
Abstract: BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes.METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression.RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013).CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections.
Published: 2023

24. Preoperative risk score (PreopScore) to predict overall survival after resection for hepatocellular carcinoma

Author: Yutaka Endo, Henrique A. Lima, Laura Alaimo, Zorays Moazzam, Zachary Brown, Chanza F. Shaikh, Francesca Ratti, Hugo P. Marques, Olivier Soubrane, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Aklile Workneh, Alfredo Guglielmi, Tom Hugh, Luca Aldrighetti, Feng Shen, Itaru Endo, and Timothy M. Pawlik
Subjects: Hepatology, Gastroenterology
Published: 2023

25. Artificial intelligence to investigate predictors and prognostic impact of time to surgery in colon cancer

Author: Laura Alaimo, Zorays Moazzam, Selamawit Woldesenbet, Henrique A. Lima, Yutaka Endo, Muhammad M. Munir, Lovette Azap, Andrea Ruzzenente, Alfredo Guglielmi, and Timothy M. Pawlik
Subjects: Oncology, Surgery, General Medicine
Published: 2023

26. TBS-Based Preoperative Score to Predict Non-transplantable Recurrence and Identify Candidates for Upfront Resection Versus Transplantation for Hepatocellular Carcinoma

Author: Henrique A. Lima, Zorays Moazzam, Yutaka Endo, Laura Alaimo, Chanza Shaikh, Muhammad Musaab Munir, Vivian Resende, Alfredo Guglielmi, Hugo P. Marques, François Cauchy, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Tom Hugh, Itaru Endo, Minoru Kitago, Feng Shen, and Timothy M. Pawlik
Subjects: Oncology, Surgery
Published: 2023

27. Predictive risk-score model to select patients with intrahepatic cholangiocarcinoma for adjuvant chemotherapy

Author: Yutaka Endo, Zorays Moazzam, Laura Alaimo, Henrique A. Lima, Muhammad M. Munir, Chanza F. Shaikh, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Minoru Kitago, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas G. Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Predictive risk-score model, adjuvant chemotherapy, Predictive risk-score model, intrahepatic cholangiocarcinoma, adjuvant chemotherapy, Hepatology, intrahepatic cholangiocarcinoma, Gastroenterology
Abstract: Background: The aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC). Methods: Patients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC. Results: Among 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04–1.31), tumor burden score (HR1.09, 95%CI 1.04–1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73–2.64), nodal disease (N1, HR3.80, 95%CI 2.02–7.15), tumor grade (HR1.88, 95%CI 1.00–3.55), and morphological subtype (HR2.19, 95%CI 1.08–4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk_model_for_AC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors. Conclusion: An online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC.
Published: 2023

28. Current Role and Future Perspectives of Immunotherapy and Circulating Factors in Treatment of Biliary Tract Cancers

Author: Simone Conci, Giovanni Catalano, Diletta Roman, Camilla Zecchetto, Eleonora Lucin, Mario De Bellis, Marzia Tripepi, Alfredo Guglielmi, Michele Milella, and Andrea Ruzzenente
Subjects: General Medicine
Published: 2023

29. The LIver SEntinel LYmph-node (LISELY) study: A prospective intraoperative real time evaluation of liver lymphatic drainage and sentinel lymph-node using near-infrared (NIR) imaging with Indocyanine Green (ICG)

Author: Andrea Ruzzenente, Simone Conci, Giulia Isa, Tommaso Campagnaro, Corrado Pedrazzani, Mario De Bellis, Ivan Marchitelli, Claudia Castelli, Sara Pecori, and Alfredo Guglielmi
Subjects: Oncology, Surgery, General Medicine
Abstract: Near-infrared (NIR) imaging with Indocyanine green (ICG) has been recently proposed for the sentinel lymph node (SLN) and lymphatic out-flow detection in several tumors. Nowadays its application in primary and secondary liver (LCs) and biliary cancers (BTCs) remains uninvestigated. A proof-of-concept prospective observational study including 18 patients underwent surgery for LCs and BTCs from September 2021 to November 2021 was carried out. The intraoperative NIR imaging with ICG was detected at predefined temporary intervals in order to identify the main lymphatic out-flow and the SLN. In 14 patients (77.8%) the lymphatic outflow pathway was visualized with a median time of 3 min after ICG injection (IQR 3-10). The SLN was detected and confirmed at the histological examination in 12 patients (66.7%). Intraoperative NIR imaging with ICG is a safe and feasible method to identify the lymphatic out-flow and SLN in LCs and BTCs.
Published: 2022

30. Sarcobesity Index Predicts Poor Disease-Specific Survival After Resection for Colorectal Cancer

Author: Cristian Conti, Giulia Turri, Gabriele Gecchele, Simone Conci, Giulia A. Zamboni, Andrea Ruzzenente, Alfredo Guglielmi, and Corrado Pedrazzani
Subjects: Sarcopenia, Sarcopenic obesity, Cancer nutrition, Intra-Abdominal Fat, Prognosis, Colorectal cancer, Visceral obesity, Colorectal surgery, Sarcobesity, Humans, Surgery, Colorectal Neoplasms, Retrospective Studies
Abstract: Sarcobesity (SO) is traditionally defined as the association between low muscle mass and obesity and has been reported to worsen prognosis after curative resection for colorectal cancer (CRC). This study aimed to propose a new definition of SO based on computed tomography measurements of the skeletal muscle area (SMA) and visceral adipose tissue (VAT) and to assess its implications on long-term survival after curative resection for stage I-III CRC.We retrospectively analyzed 506 patients with stage I-III CRC who underwent surgery between January 2010 and December 2019. Preoperative computed tomography images were analyzed and the sarcobesity index (SI) was calculated for each patient as the VAT/SMA ratio. The optimal cutoff value for predicting survival was determined using time-dependent receiver operating characteristic analysis. Overall survival and disease-specific survival (DSS) were compared between SO (SI 1.25) and non-SO (SI ≤ 1.25) patients. The rates and modes of recurrence were also compared between the two groups.Three hundred (59.3%) patients were identified to be sarcobese. No differences in short-term outcomes and administration of adjuvant chemotherapy were found, except for a longer length of stay in patients with SO. In a univariable analysis, SO was associated with a worse 5-y overall survival and DSS, considering the whole population and stages II and III separately. A multivariable analysis confirmed SO to be an independent risk factor for DSS (hazard ratio 2.29; 95% confidence interval 1.13-4.62, P = 0.02). Although the overall recurrence rate did not differ between the groups, a significantly higher rate of recurrence at multiple sites was observed in patients with SO (P = 0.01).The SI, defined as per the VAT/SMA ratio, seems to be a reliable tool for identifying patients with worse DSS after potentially curative surgery for stage I-III CRC.
Published: 2022

31. TAC score better predicts survival than the BCLC following resection of hepatocellular carcinoma

Author: Henrique A. Lima, Yutaka Endo, Zorays Moazzam, Laura Alaimo, Chanza Shaikh, Muhammad M. Munir, Vivian Resende, Alfredo Guglielmi, Hugo P. Marques, François Cauchy, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Itaru Endo, Minoru Kitago, Feng Shen, and Timothy M. Pawlik
Subjects: Oncology, Surgery, General Medicine
Abstract: Heterogeneity in hepatocellular carcinoma (HCC) still exists within the Barcelona clinic liver cancer (BCLC) subcategories. We developed a simple model to better discriminate and predict prognosis following resection.Patients who underwent curative-intent resection for HCC were identified from a multi-institutional database. Predictive factors of survival were identified to develop TAC (tumor burden score [TBS], alpha-fetoprotein [AFP], Child-Pugh CP]) score.Among 1435 patients, median TBS was 5.1 (interquartile range [IQR]: 3.2-8.1), median AFP was 18.3 ng/ml (IQR 4.0-362.5), and 1391 (96.9%) patients were classified as CP-A. Factors associated with overall survival (OS) included TBS (low: referent; medium: HR 2.26, 95% CI: 1.73-2.96; high: HR = 3.35, 95% CI: 2.22-5.07), AFP (400 ng/ml: referent;400 ng/ml: HR = 1.56, 95% CI: 1.27-1.92), and CP (A: referent; B: HR = 1.81, 95% CI: 1.12-2.92) (all p 0.05). A simplified risk score demonstrated superior concordance index, Akaike information criteria, homogeneity, and area under the curve versus BCLC (0.620 vs. 0.541; 5484.655 vs. 5536.454; 60.099 vs. 16.194; 0.62 vs. 0.55, respectively), and further stratified patients within BCLC groups relative to OS (BCLC 0, very low: 86.8%, low: 47.8%) (BCLC A, very low: 79.7%, low: 68.1%, medium: 52.5%, high: 35.6%) (BCLC B, low: 59.8%, medium: 43.7%, high: N/A).TAC is a simple, holistic score that consistently outperformed BCLC relative to discrimination power and prognostication following resection of HCC.
Published: 2022

32. A Novel Online Calculator to Predict Risk of Microvascular Invasion in the Preoperative Setting for Hepatocellular Carcinoma Patients Undergoing Curative-Intent Surgery

Author: Yutaka Endo, Laura Alaimo, Henrique A. Lima, Zorays Moazzam, Francesca Ratti, Hugo P. Marques, Olivier Soubrane, Vincent Lam, Minoru Kitago, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Aklile Workneh, Alfredo Guglielmi, Tom Hugh, Luca Aldrighetti, Itaru Endo, Timothy M. Pawlik, Endo, Yutaka, Alaimo, Laura, Lima, Henrique A, Moazzam, Zoray, Ratti, Francesca, Marques, Hugo P, Soubrane, Olivier, Lam, Vincent, Kitago, Minoru, Poultsides, George A, Popescu, Irinel, Alexandrescu, Sorin, Martel, Guillaume, Workneh, Aklile, Guglielmi, Alfredo, Hugh, Tom, Aldrighetti, Luca, Endo, Itaru, and Pawlik, Timothy M
Subjects: Oncology, Surgery
Abstract: The presence of microvascular invasion (MVI) has been highlighted as an important determinant of hepatocellular carcinoma (HCC) prognosis. We sought to build and validate a novel model to predict MVI in the preoperative setting.
Published: 2022

33. 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

Author: Laura Alaimo, Yutaka Endo, Henrique A. Lima, Zorays Moazzam, Chanza Fahim Shaikh, Andrea Ruzzenente, Alfredo Guglielmi, Francesca Ratti, Luca Aldrighetti, Hugo P. Marques, François Cauchy, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Tom Hugh, Itaru Endo, Timothy M. Pawlik, Alaimo, Laura, Endo, Yutaka, Lima, Henrique A, Moazzam, Zoray, Shaikh, Chanza Fahim, Ruzzenente, Andrea, Guglielmi, Alfredo, Ratti, Francesca, Aldrighetti, Luca, Marques, Hugo P, Cauchy, Françoi, Lam, Vincent, Poultsides, George A, Popescu, Irinel, Alexandrescu, Sorin, Martel, Guillaume, Hugh, Tom, Endo, Itaru, and Pawlik, Timothy M
Subjects: Carcinoma, Hepatocellular, Liver resection, Hepatocellular carcinoma, Liver Neoplasms, Gastroenterology, Bilirubin, Comorbidity, Prognosis, Tumor Burden, Humans, Hepatectomy, Surgery, Serum Albumin, Liver Failure, Post-hepatectomy liver failure, Retrospective Studies
Abstract: 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.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.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).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.
Published: 2022

34. The impact of tumor location on the value of lymphadenectomy for intrahepatic cholangiocarcinoma

Author: Yutaka Endo, Zorays Moazzam, Henrique A. Lima, Laura Alaimo, Muhammad M. Munir, Chanza F. Shaikh, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Minoru Kitago, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas G. Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Hepatology, Gastroenterology
Abstract: Background: The therapeutic role of lymphadenectomy (LND) for intrahepatic cholangiocarcinoma (ICC) patients remains ill-defined. We sought to analyze the therapeutic value of LND relative to tumor location and preoperative lymph node metastasis (LNM) risk. Methods: Patients who underwent curative-intent hepatic resection of ICC between 1990 and 2020 were included from a multi-institutional database. Therapeutic LND (tLND) was defined as LND that harvested ≥3 lymph nodes. Results: Among 662 patients, 178 (26.9%) individuals received tLND. Patients were categorized into central type ICC (n = 156, 23.6%) and peripheral type ICC (n = 506, 76.4%). Central type harbored multiple adverse clinicopathologic factors and worse overall survival (OS) compared with peripheral type (5-year OS, central: 27.0% vs. peripheral: 47.2%, p < 0.001). After consideration of preoperative LNM risk, patients with central type and high-risk LNM who underwent tLND survived longer than individuals who did not (5-year OS, tLND: 27.9% vs. non-tLND: 9.0%, p = 0.001), whereas tLND was not associated with better survival among patients with peripheral type ICC or low-risk LNM. The therapeutic index of hepatoduodenal ligament (HDL) and other regions was higher in central type than in peripheral type, which was more pronounced among high-risk LNM patients. Conclusions: Central type ICC with high-risk LNM should undergo LND involving regions beyond the HDL.
Published: 2023

35. Hyper accuracy three-dimensional (HA3D™) technology for planning complex liver resections: a preliminary single center experience

Author: Andrea Ruzzenente, Laura Alaimo, Simone Conci, Mario De Bellis, Andrea Marchese, Andrea Ciangherotti, Tommaso Campagnaro, and Alfredo Guglielmi
Subjects: Surgery
Abstract: Three-dimensional visualization technology (3DVT) has been recently introduced to achieve a precise preoperative planning of liver surgery. The aim of this observational study was to assess the accuracy of 3DVT for complex liver resections. 3DVT with hyper accuracy three-dimensional (HA3D™) technology was introduced at our institution on February 2020. Anatomical characteristics were collected from two-dimensional imaging (2DI) and 3DVT, while intraoperative and postoperative outcomes were recorded prospectively. A total of 62 patients were enrolled into the study. 3DVT was able to study tumor extension and liver anatomy, identifying at least one vascular variation in 37 patients (59.7%). Future remnant liver volume (FRLV) was measured using 2DI and 3DVT. The paired samples t test assessed positive correlation between the two methods (p Graphical abstract
Published: 2022

36. Factors Related to Textbook Outcome in Laparoscopic Liver Resections: a Single Western Centre Analysis

Author: Andrea Ruzzenente, Edoardo Poletto, Simone Conci, Tommaso Campagnaro, Bernardo Dalla Valle, Mario De Bellis, and Alfredo Guglielmi
Subjects: Postoperative Complications, Treatment Outcome, Liver Neoplasms, Gastroenterology, Humans, Hepatectomy, Laparoscopy, Surgery, Length of Stay, Retrospective Studies, Quality Indicators, Health Care
Abstract: Introduction The selection of the most informative quality of care indicator for laparoscopic liver surgery (LLS) is still debated; among those proposed, textbook outcome (TO) seems to provide a compositive measure of the outcomes of surgery. The aim of this study was to investigate the factors related with the TO in a cohort of patients who underwent LLS. Methods Patients who underwent LLS from 2014 to 2021 were included. TO for LLS (TOLLS) was defined as: R0 resection, absence of intraoperative incidents, severe complications, reintervention, 30-day readmission and in-hospital mortality. When also considering no prolonged length of hospital stay (LOS), the outcome was called TOLLS+. Results Four hundred twenty-one patients were included; TOLLS was achieved in 80.5%, TOLLS+ in 60.8% cases. R0 resection was obtained in 90.2% cases, intraoperative incidents occurred in 7.8%, severe complications in 5.0%, reintervention in 0.7%, readmission in 1.4% and in-hospital mortality in 0.2%. 32.5% of patients showed prolonged LOS. After univariate and multivariate analysis, factors influencing TOLLS were age (OR 0.967; p=0.003), concomitant surgery (OR 0.380; p=0.003), operative time (OR 0.996; p=0.008) and blood loss (OR 0.241; p<0.001); factors influencing TOLLS+ were ASA-score (OR 0.533; p=0.008), tumour histology (OR 0.421; p=0.021), concomitant surgery (OR 0.293; p<0.001), operative time (OR 0.997; p=0.016) and blood loss (OR 0.361; p=0.003). Conclusions TOLLS can be achieved in most patients undergoing LLR, and it seems to be influenced mostly by surgery-related factors; conversely, TOLLS+ is achieved less frequently and seems to be influenced also by patient- and tumour-related factors.
Published: 2022

37. Development and Validation of a Machine-Learning Model to Predict Early Recurrence of Intrahepatic Cholangiocarcinoma

Author: Laura Alaimo, Henrique A. Lima, Zorays Moazzam, Yutaka Endo, Jason Yang, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Minoru Kitago, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery
Abstract: Background: The high incidence of early recurrence after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a detrimental effect on overall survival (OS). Machine-learning models may improve the accuracy of outcome prediction for malignancies. Methods: Patients who underwent curative-intent hepatectomy for ICC were identified using an international database. Three machine-learning models were trained to predict early recurrence (< 12 months after hepatectomy) using 14 clinicopathologic characteristics. The area under the receiver operating curve (AUC) was used to assess their discrimination ability. Results: In this study, 536 patients were randomly assigned to training (n = 376, 70.1%) and testing (n = 160, 29.9%) cohorts. Overall, 270 (50.4%) patients experienced early recurrence (training: n = 150 [50.3%] vs testing: n = 81 [50.6%]), with a median tumor burden score (TBS) of 5.6 (training: 5.8 [interquartile range {IQR}, 4.1–8.1] vs testing: 5.5 [IQR, 3.7–7.9]) and metastatic/undetermined nodes (N1/NX) in the majority of the patients (training: n = 282 [75.0%] vs testing n = 118 [73.8%]). Among the three different machine-learning algorithms, random forest (RF) demonstrated the highest discrimination in the training/testing cohorts (RF [AUC, 0.904/0.779] vs support vector machine [AUC, 0.671/0.746] vs logistic regression [AUC, 0.668/0.745]). The five most influential variables in the final model were TBS, perineural invasion, microvascular invasion, CA 19-9 lower than 200 U/mL, and N1/NX disease. The RF model successfully stratified OS relative to the risk of early recurrence. Conclusions: Machine-learning prediction of early recurrence after ICC resection may inform tailored counseling, treatment, and recommendations. An easy-to-use calculator based on the RF model was developed and made available online.
Published: 2023

38. The impact of recurrence timing and tumor burden score on overall survival among patients undergoing repeat hepatectomy for colorectal liver metastases

Author: Yutaka Endo, Belisario Ortiz Rueda, Selamawit Woldesenbet, Muhammad Musaab Munir, Henrique A. Lima, Erryk S. Katayama, Chanza F. Shaikh, Alfredo Guglielmi, Andrea Ruzzenente, Luca Aldrighetti, Sorin Alexandrescu, Minoru Kitago, George Poultsides, Kazunari Sasaki, Federico Aucejo, and Timothy M. Pawlik
Subjects: Oncology, Surgery, General Medicine
Published: 2023

39. ASO Visual Abstract: Impact of Staging Concordance and Downstaging after Neoadjuvant Therapy on Survival Following Resection of Intrahepatic Cholangiocarcinoma: A Bayesian Analysis

Author: Laura Alaimo, Zorays Moazzam, Henrique A. Lima, Yutaka Endo, Selamawit Woldesenbet, Aslam Ejaz, Jordan Cloyd, Alfredo Guglielmi, Andrea Ruzzenente, and Timothy M. Pawlik
Subjects: Oncology, Surgery
Published: 2023

40. Impact of Staging Concordance and Downstaging After Neoadjuvant Therapy on Survival Following Resection of Intrahepatic Cholangiocarcinoma: A Bayesian Analysis

Author: Laura Alaimo, Zorays Moazzam, Henrique A. Lima, Yutaka Endo, Selamawit Woldesenbet, Aslam Ejaz, Jordan Cloyd, Alfredo Guglielmi, Andrea Ruzzenente, and Timothy M. Pawlik
Subjects: Oncology, Surgery
Published: 2023

41. ASO Visual Abstract: The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma

Author: Laura Alaimo, Zorays Moazzam, Yutaka Endo, Henrique A. Lima, Swatika P. Butey, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Minoru Kitago, Alex Kim, Aslam Ejaz, Joal Beane, Jordan Cloyd, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery
Published: 2023

42. Combined Tumor Burden Score and Carbohydrate Antigen 19-9 Grading System to Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma

Author: Zorays Moazzam, Laura Alaimo, Yutaka Endo, Henrique A Lima, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W Bauer, Sorin Alexandrescu, George A Poultsides, Shishir K Maithel, Hugo P Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Jordan Cloyd, Aslam Ejaz, Timothy M Pawlik, and Surgery
Subjects: Surgery
Abstract: BACKGROUND: The interplay of carbohydrate antigen 19-9 (CA19-9) and tumor burden score (TBS) within intrahepatic cholangiocarcinoma remains ill-defined. We evaluated the roles of TBS and CA19-9 relative to overall survival (OS) and recurrence, as well as the predictive ability of the combined TBS and CA19-9 (CTC) grading system. STUDY DESIGN: Patients undergoing liver resection for intrahepatic cholangiocarcinoma between 2000 and 2020 were identified using a multi-institutional database. The impact of CA19-9 and TBS on 5-year OS and 3-year recurrence was assessed, along with the prognostic accuracy of the CTC grading system (ie the composite score of CA19-9 level and TBS). RESULTS: Among 831 patients, the median age was 58.2 years and 482 (58.0%) were male. The median [IQR] CA19-9 level was 49.7 [17.0, 221.0] U/mL and TBS was 6.1 [4.1, 8.3]. Median [IQR] and 5-year OS were 36.9 [32.3, 43.1] months and 38.9%, respectively; 3-year recurrence was 68.9%. Five-year survival varied relative to CA19-9 (low vs high, 49.0% vs 19.7%) and TBS (low vs high, 53.6% vs 26.9%) (p < 0.001 for both). On multivariable analysis, high CA19-9 (hazard ratio [HR] 2.02, 95% CI 1.64 to 2.49) and high TBS (HR 1.64, 95% CI 1.32 to 2.06) remained independently associated with OS. In turn, the CTC grading score stratified 5-year OS (low vs intermediate vs high CTC, 57.7% vs 39.9% vs 12.6%; p < 0.001) and remained an independent prognostic factor (referent, low CTC; [intermediate CTC] HR 1.54, 95% CI 1.18 to 2.01; [high CTC] HR 3.28, 95% CI 2.47 to 4.36). CONCLUSIONS: The interplay between tumor morphology and biology dictates long-term prognosis after liver resection for intrahepatic cholangiocarcinoma. Prognostic models such as the CTC grading system may inform discussions around prognosis, as well as help identify which patients with ICC may benefit more from neoadjuvant chemotherapy rather than up-front surgery.
Published: 2023

43. Albumin-Bilirubin Grade and Tumor Burden Score Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma After Hepatic Resection: a Multi-Institutional Analysis

Author: Muhammad Musaab Munir, Yutaka Endo, Henrique A. Lima, Laura Alaimo, Zorays Moazzam, Chanza Shaikh, George A. Poultsides, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, Minoru Kitago, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Gastroenterology, Surgery
Abstract: BACKGROUND: 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 10 days) (OR 2.80, 95%CI 1.62-4.82; p 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.
Published: 2023

44. ASO Visual Abstract: Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma

Author: Laura Alaimo, Zorays Moazzam, Yutaka Endo, Henrique A. Lima, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W. Bauer, Sorin Alexandrescu, George A. Poultsides, Shishir K. Maithel, Hugo P. Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Timothy M. Pawlik, and Surgery
Subjects: Oncology, Surgery
Published: 2023

45. A machine learning analysis of difficulty scoring systems for laparoscopic liver surgery

Author: Andrea Ruzzenente, Fabio Bagante, Edoardo Poletto, Tommaso Campagnaro, Simone Conci, Mario De Bellis, Corrado Pedrazzani, and Alfredo Guglielmi
Subjects: Machine Learning, Postoperative Complications, Patient selection, Difficulty scoring system, Liver Neoplasms, Humans, Hepatectomy, Textbook outcome, Laparoscopy, Surgery, Laparoscopic liver resection, Length of Stay, Retrospective Studies
Abstract: Introduction In the last decade, several difficulty scoring systems (DSS) have been proposed to predict technical difficulty in laparoscopic liver resections (LLR). The present study aimed to investigate the ability of four DSS for LLR to predict operative, short-term, and textbook outcomes. Methods Patients who underwent LLR at a single tertiary referral center from January 2014 to June 2020 were included in the present study. Four DSS for LLR (Halls, Hasegawa, Kawaguchi, and Iwate) were investigated to test their ability to predict operative and postoperative complications. Machine learning algorithms were used to identify the most important DSS associated with operative and short-term outcomes. Results A total of 346 patients were included in the analysis, 28 (8.1%) patients were converted to open surgery. A total of 13 patients (3.7%) had severe (Clavien–Dindo ≥ 3) complications; the incidence of prolonged length of stay (> 5 days) was 39.3% (n = 136). No patients died within 90 days after the surgery. According to Halls, Hasegawa, Kawaguchi, and Iwate scores, 65 (18.8%), 59 (17.1%), 57 (16.5%), and 112 (32.4%) patients underwent high difficulty LLR, respectively. In accordance with a random forest algorithm, the Kawaguchi DSS predicted prolonged length of stay, high blood loss, and conversions and was the best performing DSS in predicting postoperative outcomes. Iwate DSS was the most important variable associated with operative time, while Halls score was the most important DSS predicting textbook outcomes. No one of the DSS investigated was associated with the occurrence of complication. Conclusions According to our results DDS are significantly related to surgical complexity and short-term outcomes, Kawaguchi and Iwate DSS showed the best performance in predicting operative outcomes, while Halls score was the most important variable in predicting textbook outcome. Interestingly, none of the DSS showed any correlation with or importance in predicting overall and severe postoperative complications. Graphical abstract
Published: 2022

46. Surgical Treatment of Liver Metastases from Pancreatic Adenocarcinoma: Still a Taboo? A Nomogram to Predict Overall Survival Developed on a National Cohort

Author: Ratti, F., primary, Crippa, S., additional, Mazzaferro, V., additional, Cescon, M., additional, Jovine, E., additional, Zerbi, A., additional, Boggi, U., additional, Bassi, C., additional, Falconi, M., additional, Aldrighetti, L., additional, Marco, Vivarelli, additional, Alfredo, Guglielmi, additional, Alessandro, Ferrero, additional, Giovanni, Ferrari, additional, Giorgio, Ercolani, additional, Pierluigi, Di Sebastiano, additional, Roberto, Coppola, additional, Luca, Morelli, additional, Giuseppe, Malleo, additional, Giulia, Gasparini, additional, Giulio, Belfiori, additional, Rebecca, Marino, additional, Niccoló, Napoli, additional, Giovanni, Capretti, additional, Matteo, Zanello, additional, Matteo, Serenari, additional, and Carlo, Sposito, additional
Published: 2023
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47. Cornerstones and Divergencies in the Implementation and Use of Liver Hypertrophy Techniques in Italy: Results from a Nationwide Survey for National Registry Set Up

Author: Ratti, F., primary, Serenari, M., additional, Aldrighetti, L., additional, Jovine, E., additional, Alfonso, Avolio, additional, Giacomo, Batignani, additional, Ugo, Boggi, additional, Alberto, Brolese, additional, Lucio, Caccamo, additional, Andrea, Celotti, additional, Matteo, Cescon, additional, Umberto, Cillo, additional, Nicola, Cinardi, additional, Christian, Cotsoglou, additional, Raffaele, Dalla Valle, additional, Luciano, De Carlis, additional, Paolo, De Simone, additional, Fabrizio, Di Benedetto, additional, Giorgio, Ercolani, additional, Maria, Ettorre Giuseppe, additional, Massimo, Fedi, additional, Alessandro, Ferrero, additional, Antonio, Giuliani, additional, Felice, Giuliante, additional, Gianluca, Grazi, additional, Salvatore, Gruttadauria, additional, Alfredo, Guglielmi, additional, Francesco, Izzo, additional, Quirino, Lai, additional, Dario, Lorenzin, additional, Marcello, Maestri, additional, Marco, Massani, additional, Vincenzo, Mazzaferro, additional, Riccardo, Memeo, additional, Bruno, Nardo, additional, Nazario, Portolani, additional, Aldo, Rocca, additional, Renato, Romagnoli, additional, Fabrizio, Romano, additional, Edoardo, Saladino, additional, Giuseppe, Tisone, additional, Roberto, Troisi, additional, Luigi, Veneroni, additional, Giovanni, Vennarecci, additional, Luca, Viganò, additional, Giuseppe, Viola, additional, Marco, Vivarelli, additional, and Giacomo, Zanus, additional
Published: 2023
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48. Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry

Author: Felice Giuliante, Francesca Ratti, Elena Panettieri, Vincenzo Mazzaferro, Alfredo Guglielmi, Giuseppe M. Ettorre, Salvatore Gruttadauria, Fabrizio Di Benedetto, Umberto Cillo, Luciano De Carlis, Raffaele Dalla Valle, Alessandro Ferrero, Roberto Santambrogio, Francesco Ardito, and Luca Aldrighetti
Subjects: small hepatocellular carcinoma, Hepatology, Settore MED/18 - CHIRURGIA GENERALE, Gastroenterology, laparoscopic liver resection
Published: 2023

49. Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study

Author: Eduardo A. Vega, Timothy E. Newhook, Sebastian Mellado, Andrea Ruzzenente, Masayuki Okuno, Mario De Bellis, Elena Panettieri, M. Usman Ahmad, Ignacio Merlo, Jesus Rojas, Agostino M. De Rose, Hiroto Nishino, Andrew J. Sinnamon, Matteo Donadon, Marit S. Hauger, Oscar A. Guevara, Cesar Munoz, Jason W. Denbo, Yun Shin Chun, Hop S. Tran Cao, Rodrigo Sanchez Claria, Ching-Wei D. Tzeng, Xabier De Aretxabala, Marcelo Vivanco, Kristoffer W. Brudvik, Satoru Seo, Juan Pekolj, George A. Poultsides, Guido Torzilli, Felice Giuliante, Daniel A. Anaya, Alfredo Guglielmi, Eduardo Vinuela, and Jean-Nicolas Vauthey
Subjects: = 22%, and rate of grade &gt, GBC surgical approaches, R1 margin rate &lt, =+IIIa%29%2E+Median+length+of+postoperative+hospital+stay+was+6+days+%28interquartile+range+4-8+days%29%2E+Benchmark+values+included+>=+4+lymph+nodes+retrieved%2C+estimated+intraoperative+blood+loss+<=+350+mL%2C+perioperative+blood+transfusion+rate+<=+13%25%2C+operative+time+<=+332+min%2C+length+of+hospital+stay+<=+8+days%2C+R1+margin+rate+<=+7%25%2C+complication+rate+<=+22%25%2C+and+rate+of+grade+>=+IIIa+complications+<=+11%25%2EConclusionsSurgery+for+GBC+remains+associated+with+significant+morbidity%2E+The+availability+of+benchmark+values+may+facilitate+comparisons+in+future+analyses+among+GBC+patients%2C+GBC+surgical+approaches%2C+and+centers+performing+GBC+surgery%22">BackgroundHigh-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population.Patients and MethodsThis study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group.ResultsOf 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade >= IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included >= 4 lymph nodes retrieved, estimated intraoperative blood loss <= 350 mL, perioperative blood transfusion rate <= 13%, operative time <= 332 min, length of hospital stay <= 8 days, R1 margin rate <= 7%, complication rate <= 22%, and rate of grade >= IIIa complications <= 11%.ConclusionsSurgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade &gt, 50 patients (20%) experienced complications within 90 days after surgery, = IIIa complications &lt, = IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included &gt, = 11%.ConclusionsSurgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, perioperative blood transfusion rate &lt, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group.ResultsOf 906 patients who underwent curative-intent GBC surgery during the study period, = 332 min, and centers performing GBC surgery, = 8 days, complication rate &lt, = 13%, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, Oncology, BackgroundHigh-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population.Patients and MethodsThis study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, estimated intraoperative blood loss &lt, = 7%, = 350 mL, operative time &lt, Surgery, = 4 lymph nodes retrieved, length of hospital stay &lt
Published: 2023

50. Molecular characterization of extrahepatic cholangiocarcinoma: perihilar and distal tumors display divergent genomic and transcriptomic profiles

Author: Michele Simbolo, Samantha Bersani, Caterina Vicentini, Sergio V. Taormina, Chiara Ciaparrone, Fabio Bagante, Borislav Rusev, Giovanni Centonze, Marina Montresor, Matteo Brunelli, Serena Pedron, Andrea Mafficini, Gaetano Paolino, Paola Mattiolo, Simone Conci, Massimo Milione, Alfredo Guglielmi, Andrea Ruzzenente, Aldo Scarpa, and Claudio Luchini
Subjects: Pharmacology, molecular profiling, Clinical Biochemistry, Genomics, Klatksin, Cholangiocarcinoma, extrahepatic, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Mutation, Drug Discovery, Tumor Microenvironment, Humans, Molecular Medicine, Precision Medicine, Transcriptome, biliary
Abstract: Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles.The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes. A subgroup of cases, representative of each subtype, was further investigated using transcriptomic analysis. Bioinformatics tools were applied for clustering and pathway analysis and defining the immune composition of the tumor microenvironment.PHCC had more frequent KRAS mutations (p = 0.0047), whereas TP53 mutations were more common in DECC (p = 0.006). Potentially actionable alterations included high-tumor mutational burden and/or microsatellite instability (7.1%), PI3KCA mutations (8.1%), and MYC (10.1%) and ERBB2 amplification (5.1%). The transcriptomic profiles showed the presence of three distinct clusters, which followed the anatomic origin and differed in immune microenvironment. DECC appeared to contain two distinct tumor subgroups, one enriched for druggable alterations and one lacking actionable opportunities.This study provides new insights into the molecular landscape and the actionable alterations of ECC. Our findings represent a step toward improved ECC molecular taxonomy and therapeutic strategies for precision oncology.
Published: 2021

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