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162. Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

Author

Aldrighetti, aEmail Author, L., Boggi, U. b., Falconi, M. c., Giuliante, F. d., Cipriani, F. a., Ratti, Torzilli, G. e., Abu, Hilal, Andrianello, Anselmo, Ardito, Gian, L. B., Banchini, Barabino, Barberis, Bassi, Batignani, Battiston, Belli, Berti, Bianco, Brolese, Brozzetti, Butturini, Calise, Carabott, Capretti, Casadei, Cescon, Cesaretti, Cillo, Cinardi, Colledan, Coppola, Cotsoglou, Crippa, Bona, E. D., Valle, R. D., Angelis, De, Carlis, De, Benedetto, Di, Sebastiano, Di, Dova, Ercolani, Esposito, Giuseppe, M. E., Fabris, Ferrero, Frena, Frigerio, Gianotti, Giuliani, Grazi, Gringeri, Griseri, Gruttadauria, Guglielmi, Izzo, Jovine, Lanza, Malleo, Manzini, Massani, Mazzaferro, Memeo, Minni, Morelli, Nappo, Nardo, Orlando, Partelli, Patriti, Patrone, Percivale, Piccolo, Ravaioli, Reggiani, Risaliti, Rocca, A, Romagnoli, Romano, Russolillo, Ruzzenente, Saladino, Salvia, Santambrogio, Tarchi, Troci, Troisi, Urbani, Veneroni, Vennarecci, Vigano, Viola, Vistoli, Vivarelli, Zanello, Zanus, Zerbi, Italian Association of HepatoBilioPancreatic Surgeons-AICEP, Aldrighetti, L., Boggi, U., Falconi, M., Giuliante, F., Cipriani, F., Ratti, F., Torzilli, G., Abu Hilal, M., Andrianello, S., Anselmo, A., Ardito, F., Gian, L. B., Banchini, F., Barabino, M., Barberis, A., Bassi, C., Batignani, G., Battiston, C., Belli, A., Berti, S., Bianco, P., Brolese, A., Brozzetti, S., Butturini, G., Calise, F., Carabott, K., Capretti, G., Casadei, R., Cescon, M., Cesaretti, M., Cillo, U., Cinardi, N., Colledan, M., Coppola, A., Cotsoglou, C., Crippa, S., Bona, E. D., Valle, R. D., De Angelis, M., De Carlis, L., Di Benedetto, F., Di Sebastiano, P., Dova, L., Ercolani, G., Esposito, A., Giuseppe, M. E., Fabris, A., Ferrero, A., Frena, A., Frigerio, I., Gianotti, L., Giuliani, A., Grazi, G., Gringeri, E., Griseri, G., Gruttadauria, S., Guglielmi, A., Izzo, F., Jovine, E., Lanza, E., Malleo, G., Manzini, L., Massani, M., Mazzaferro, V., Memeo, R., Minni, F., Morelli, L., Nappo, G., Nardo, B., Orlando, F., Partelli, S., Patriti, A., Patrone, R., Percivale, A., Piccolo, G., Ravaioli, M., Reggiani, P., Risaliti, M., Rocca, A., Romagnoli, R., Romano, F., Russolillo, N., Ruzzenente, A., Saladino, E., Salvia, R., Santambrogio, R., Tarchi, P., Troci, A., Troisi, R., Urbani, L., Veneroni, L., Vennarecci, G., Vigano, L., Viola, M., Vistoli, F., Vivarelli, M., Zanello, M., Zanus, G., Zerbi, A., Aldrighetti L., Boggi U., Falconi M., Giuliante F., Cipriani F., Ratti F., Torzilli G., Abu Hilal M., Andrianello S., Anselmo A., Ardito F., Gian L.B., Banchini F., Barabino M., Barberis A., Bassi C., Batignani G., Battiston C., Belli A., Berti S., Bianco P., Brolese A., Brozzetti S., Butturini G., Calise F., Carabott K., Capretti G., Casadei R., Cescon M., Cesaretti M., Cillo U., Cinardi N., Colledan M., Coppola A., Cotsoglou C., Crippa S., Bona E.D., Valle R.D., De Angelis M., De Carlis L., Di Benedetto F., Di Sebastiano P., Dova L., Ercolani G., Esposito A., Giuseppe M.E., Fabris A., Ferrero A., Frena A., Frigerio I., Gianotti L., Giuliani A., Grazi G., Gringeri E., Griseri G., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Lanza E., Malleo G., Manzini L., Massani M., Mazzaferro V., Memeo R., Minni F., Morelli L., Nappo G., Nardo B., Orlando F., Partelli S., Patriti A., Patrone R., Percivale A., Piccolo G., Ravaioli M., Reggiani P., Risaliti M., Rocca A., Romagnoli R., Romano F., Russolillo N., Ruzzenente A., Saladino E., Salvia R., Santambrogio R., Tarchi P., Troci A., Troisi R., Urbani L., Veneroni L., Vennarecci G., Vigano L., Viola M., Vistoli F., Vivarelli M., Zanello M., Zanus G., and Zerbi A.

Subjects
Future studies, Settore MED/18 - CHIRURGIA GENERALE, Crisis management, Nationwide survey, 0302 clinical medicine, Pandemic, Pancrea, Medicine, Viral, Minimally invasive procedures, Liver Disease, Liver Diseases, COVID-19, Liver, Minimally invasive, Pancreas, Biliary Tract Diseases, Health Care Surveys, Humans, Italy, Pancreatic Diseases, Coronavirus Infections, Minimally Invasive Surgical Procedures, Pandemics, Pneumonia, Viral, 030220 oncology & carcinogenesis, Esophagus Resection, Original Article, 030211 gastroenterology & hepatology, Biliary Tract Disease, Human, Prioritization, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), NO, 03 medical and health sciences, High Volume Hospital, Centralization, LS7_4, Coronavirus Infection, business.industry, Minimally Invasive Surgical Procedure, Pneumonia, Surgery, Health Care Survey, Invasive surgery, Pancreatic Disease, business
Abstract

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. Electronic supplementary material The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.

Published
2020
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171. Biomarker responses in cyprinids of the middle stretch of the River Po, Italy

Author

Arillo, A., Arlati, P., Melodia, F., Vigano, L., and Monti, C.

Subjects
BIOTRANSFORMATION (Metabolism)
Abstract

Fish belonging to three species of cyprinids, that is, barbel (Barbus plebejus), chub (Leuciscus cephalus), and Italian nase (Chondrostoma soetta), were collected from two sites of the River Po, located upstream and downstream from the confluence of one of its middle-reach polluted tributaries, the River Lambro. The two groups of individuals caught for each species were analyzed and compared for several microsomal and cytosolic biochemical markers. The enzymatic activities assayed in fish liver included ethoxyresorufin O-deethylase (EROD), aminopyrine-N-demethylase (APDM), uridine diphosphate glucuronyltransferase (UDPGT), glutathione S-transferase (GST), glutathione reductase. and glutathione peroxidase. In addition, the contents of reduced glutathione and nonprotein thiols were measured. Despite some differences among species, all microsomal activities (EROD, APDM, UDPGT) were found to be significantly induced in fish living downstream the River Lambro. With the exception of a higher GST enzyme activity of barbel from the downstream reach, no significant modification was evident in any of the tested cytosolic biomarkers. Results showed that barbel and nase better discriminated the two reaches of the River Po. In general, the alterations observed in feral fish are consistent with the results found in previous studies conducted with rainbow trout (Oncorhynchus mykiss) under both laboratory and field conditions in the same middle reach of the River Po. All of the data indicate that the downstream tract of the main river is exposed to the load of pollutants transported by the River Lambro, including known inducers such as polychlorinated biphenyls and polycyclic aromatic hydrocarbons (PAHs). The latter were analyzed in sediments sampled at the two sites of fish collection, and the downstream sediment showed the highest concentrations of PAHs, although their levels are comparable to those present in moderately polluted locations. Regardless of the site of exposure, bar [ABSTRACT FROM AUTHOR]

Published
1998

173. The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology

Author

Antonino Spinelli, Gaya Spolverato, Ugo Elmore, S. Berti, Giorgio Ercolani, Nadia Russolillo, Ugo Boggi, L. Vincenti, Simone Nicosia, Andrea Laurenzi, Paolo De Paolis, Giuseppe Maria Ettorre, Agostino Maria De Rose, Luca Aldrighetti, Giovanni Vennarecci, Pierluigi Marini, Matteo Cescon, Michela Mineccia, Umberto Cillo, Francesco Marchegiani, Aldo Rocca, Francesco Minni, Luciano De Carlis, Alfredo Guglielmi, Paolo Delrio, Salvatore Gruttadauria, Riccardo Rosati, Francesco Izzo, Domenico D'Ugo, Vincenzo Bottino, Maurizio Degiuli, Giulio Belli, Fulvio Calise, Vincenzo Mazzaferro, Luca Viganò, Francesco Corcione, Fabrizio Di Benedetto, Riccardo Pellicci, Marco Filauro, Alessandro Ferrero, Andrea Muratore, Marco Massani, Federica Cipriani, Guido Torzilli, Matteo Cimino, Felice Giuliante, Elio Jovine, Rocca, A, Cipriani, F, Belli, G, Berti, S, Boggi, U, Bottino, V, Cillo, U, Cescon, M, Cimino, M, Corcione, F, De Carlis, L, Degiuli, M, De Paolis, P, De Rose, A, D'Ugo, D, Di Benedetto, F, Elmore, U, Ercolani, G, Ettorre, G, Ferrero, A, Filauro, M, Giuliante, F, Gruttadauria, S, Guglielmi, A, Izzo, F, Jovine, E, Laurenzi, A, Marchegiani, F, Marini, P, Massani, M, Mazzaferro, V, Mineccia, M, Minni, F, Muratore, A, Nicosia, S, Pellicci, R, Rosati, R, Russolillo, N, Spinelli, A, Spolverato, G, Torzilli, G, Vennarecci, G, Vigano, L, Vincenti, L, Delrio, P, Calise, F, Aldrighetti, L, Rocca, Aldo, Cipriani, Federica, Belli, Giulio, Berti, Stefano, Boggi, Ugo, Bottino, Vincenzo, Cillo, Umberto, Cescon, Matteo, Cimino, Matteo, Corcione, Francesco, De Carlis, Luciano, Degiuli, Maurizio, De Paolis, Paolo, De Rose, Agostino Maria, D’Ugo, Domenico, Di Benedetto, Fabrizio, Elmore, Ugo, Ercolani, Giorgio, Ettorre, Giuseppe M., Ferrero, Alessandro, Filauro, Marco, Giuliante, Felice, Gruttadauria, Salvatore, Guglielmi, Alfredo, Izzo, Francesco, Jovine, Elio, Laurenzi, Andrea, Marchegiani, Francesco, Marini, Pierluigi, Massani, Marco, Mazzaferro, Vincenzo, Mineccia, Michela, Minni, Francesco, Muratore, Andrea, Nicosia, Simone, Pellicci, Riccardo, Rosati, Riccardo, Russolillo, Nadia, Spinelli, Antonino, Spolverato, Gaya, Torzilli, Guido, Vennarecci, Giovanni, Viganò, Luca, Vincenti, Leonardo, Delrio, Paolo, Calise, Fulvio, Aldrighetti, Luca, Rocca A., Cipriani F., Belli G., Berti S., Boggi U., Bottino V., Cillo U., Cescon M., Cimino M., Corcione F., De Carlis L., Degiuli M., De Paolis P., De Rose A.M., D'Ugo D., Di Benedetto F., Elmore U., Ercolani G., Ettorre G.M., Ferrero A., Filauro M., Giuliante F., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Laurenzi A., Marchegiani F., Marini P., Massani M., Mazzaferro V., Mineccia M., Minni F., Muratore A., Nicosia S., Pellicci R., Rosati R., Russolillo N., Spinelli A., Spolverato G., Torzilli G., Vennarecci G., Vigano L., Vincenti L., Delrio P., Calise F., and Aldrighetti L.

Subjects
Synchronous colorectal liver metastases, medicine.medical_specialty, Consensus, Colorectal cancer, Delphi method, Consensu, Colorectal Neoplasm, 030230 surgery, law.invention, Metastasis, Standard procedure, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Minimally invasive surgery, medicine, Hepatectomy, Humans, Italy, Colorectal Neoplasms, Liver Neoplasms, computer.programming_language, business.industry, General surgery, medicine.disease, Chemotherapy regimen, Surgery, Systematic review, 030220 oncology & carcinogenesis, business, computer, Delphi, Synchronous colorectal liver metastase, Human
Abstract

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15–25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients’ selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

Published
2021

174. Multicentre evaluation of case volume in minimally invasive hepatectomy

Author

L Viganò, M Cimino, L Aldrighetti, A Ferrero, U Cillo, A Guglielmi, G M Ettorre, F Giuliante, R Dalla Valle, V Mazzaferro, E Jovine, L De Carlis, F Calise, G Torzilli, F Ratti, E Gringeri, N Russolillo, G B Levi Sandri, F Ardito, U Boggi, S Gruttadauria, F Di Benedetto, G E Rossi, S Berti, G Ceccarelli, L Vincenti, G Belli, F Zamboni, A Coratti, P Mezzatesta, R Santambrogio, G Navarra, A Giuliani, A D Pinna, A Parisi, M Colledan, A Slim, A Antonucci, G L Grazi, A Frena, G Sgroi, A Brolese, L Morelli, A Floridi, A Patriti, L Veneroni, L Boni, P Maida, G Griseri, M Filauro, S Guerriero, G Tisone, R Romito, U Tedeschi, G Zimmitti, Vigano L., Cimino M., Aldrighetti L., Ferrero A., Cillo U., Guglielmi A., Ettorre G.M., Giuliante F., Dalla Valle R., Mazzaferro V., Jovine E., De Carlis L., Calise F., Torzilli G., Ratti F., Gringeri E., Russolillo N., Levi Sandri G.B., Ardito F., Boggi U., Gruttadauria S., Di Benedetto F., Rossi G.E., Berti S., Ceccarelli G., Vincenti L., Belli G., Zamboni F., Coratti A., Mezzatesta P., Santambrogio R., Navarra G., Giuliani A., Pinna A.D., Parisi A., Colledan M., Slim A., Antonucci A., Grazi G.L., Frena A., Sgroi G., Brolese A., Morelli L., Floridi A., Patriti A., Veneroni L., Boni L., Maida P., Griseri G., Filauro M., Guerriero S., Tisone G., Romito R., Tedeschi U., Zimmitti G., Vigano, L, Cimino, M, Aldrighetti, L, Ferrero, A, Cillo, U, Guglielmi, A, Ettorre, G, Giuliante, F, Dalla Valle, R, Mazzaferro, V, Jovine, E, De Carlis, L, Calise, F, Torzilli, G, Ratti, F, Gringeri, E, Russolillo, N, Levi Sandri, G, Ardito, F, Boggi, U, Gruttadauria, S, Di Benedetto, F, Rossi, G, Berti, S, Ceccarelli, G, Vincenti, L, Belli, G, Zamboni, F, Coratti, A, Mezzatesta, P, Santambrogio, R, Navarra, G, Giuliani, A, Pinna, A, Parisi, A, Colledan, M, Slim, A, Antonucci, A, Grazi, G, Frena, A, Sgroi, G, Brolese, A, Morelli, L, Floridi, A, Patriti, A, Veneroni, L, Boni, L, Maida, P, Griseri, G, Filauro, M, Guerriero, S, Tisone, G, Romito, R, Tedeschi, U, Zimmitti, G, Vigano, L., Cimino, M., Aldrighetti, L., Ferrero, A., Cillo, U., Guglielmi, A., Ettorre, G. M., Giuliante, F., Dalla Valle, R., Mazzaferro, V., Jovine, E., De Carlis, L., Calise, F., Torzilli, G., Ratti, F., Gringeri, E., Russolillo, N., Levi Sandri, G. B., Ardito, F., Boggi, U., Gruttadauria, S., Di Benedetto, F., Rossi, G. E., Berti, S., Ceccarelli, G., Vincenti, L., Belli, G., Zamboni, F., Coratti, A., Mezzatesta, P., Santambrogio, R., Navarra, G., Giuliani, A., Pinna, A. D., Parisi, A., Colledan, M., Slim, A., Antonucci, A., Grazi, G. L., Frena, A., Sgroi, G., Brolese, A., Morelli, L., Floridi, A., Patriti, A., Veneroni, L., Boni, L., Maida, P., Griseri, G., Filauro, M., Guerriero, S., Tisone, G., Romito, R., Tedeschi, U., and Zimmitti, G.

Subjects
Aged, Female, Hepatectomy, Humans, Italy, Liver Neoplasms, Male, Minimally Invasive Surgical Procedures, Registries, Retrospective Studies, Treatment Outcome, Liver surgery, Hepatic resection, Settore MED/18 - CHIRURGIA GENERALE, medicine.medical_treatment, Proposal, laparoscopy, Metastases, Liver resections, 0302 clinical medicine, minimally invasive liver surgery, case volume, Case volume, Laparascopic Liver Resection, minimally invasive hepatectomy, liver resections, 030220 oncology & carcinogenesis, high-volume centres, 030211 gastroenterology & hepatology, hepatectomy, laparoscopy, liver resections, Hepatocellular-Carcinome, medicine.medical_specialty, Outcomes, NO, 03 medical and health sciences, Hospital volume, medicine, minimally invasive, hepatectomy, LS7_4, business.industry, Retrospective cohort study, Laparascopic Liver Resection, Hepatocellular-Carcinome, Surgery, Outcomes, Metastases, Difficulty, Proposal, hepatectomy, Surgery, Severe morbidity, business, Difficulty
Abstract

Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known.Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month).A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent).A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally‐invasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes.Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumen‐resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.

Published
2020

175. Outcomes of enhanced one-stage ultrasound-guided hepatectomy for bilobar colorectal liver metastases compared to those of ALPPS: a multicenter case-match analysis

Author

Matteo Cescon, Umberto Cillo, Luca Viganò, Claudia Benini, Alessandro Ferrero, Elio Jovine, Luca Aldrighetti, Marco Massani, Matteo Cimino, Guido Torzilli, Matteo Serenari, Giuseppe Maria Ettorre, Torzilli, G., Serenari, M., Vigano, L., Cimino, M., Benini, C., Massani, M., Ettorre, G. M., Cescon, M., Ferrero, A., Cillo, U., Aldrighetti, L., Jovine, E., Torzilli G., Serenari M., Vigano L., Cimino M., Benini C., Massani M., Ettorre G.M., Cescon M., Ferrero A., Cillo U., Aldrighetti L., and Jovine E.

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Portal vein ligation, 030230 surgery, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Preoperative chemotherapy, Hepatectomy, Humans, Hospital Mortality, Aged, Retrospective Studies, Ultrasonography, Hepatology, business.industry, Patient Selection, Liver Neoplasms, Gastroenterology, One stage, Retrospective cohort study, Perioperative, Ultrasound guided, Surgery, Match analysis, Survival Rate, Treatment Outcome, colorectal liver metastases, liver failure, ALPPS, hepatectomy, Italy, Surgery, Computer-Assisted, 030220 oncology & carcinogenesis, Female, business, Colorectal Neoplasms, Follow-Up Studies
Abstract

Background In case of bilobar colorectal liver metastases (CLM) associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed. Enhanced one-stage ultrasound-guided hepatectomy (e-OSH) may represent a further solution for these patients. Aim of this study was to compare by case-match analyses the outcome of ALPPS and e-OSH. Methods Between 2012 and 2017, patients undergoing ALPPS for bilobar CLM were matched 1:2 with patients receiving e-OSH. Patients were matched according to the Fong Score (1–3/4–5), the number of CLM (3–7/≥8), the number of CLM in the left liver (1–2/≥3) and preoperative chemotherapy. All the patients in the e-OSH group had a right -sided major vascular contact. The main endpoints of the study were perioperative outcomes, overall (OS) and disease-free survival (DFS). Results Seventy-eight patients were selected (26 ALPPS and 52 e-OSH) based on matching process. The two treatments differed significantly in major morbidity (26.9% ALPPS vs 7.7% e-OSH, p = 0.017). Median OS (31.7 vs 32.6 months) and DFS (10.6 vs 7.8 months) were comparable between the two groups. Conclusions This study demonstrates that ALPPS and e-OSH for bilobar CLM achieve comparable long-term results, despite higher morbidity reported after ALPPS. These findings should drive to reposition e-OSH in managing these patients.

Published
2019

176. Minor Hepatectomies: Focusing a Blurred Picture: Analysis of the Outcome of 4471 Open Resections in Patients Without Cirrhosis

Author

Viganò, L, Torzilli, G, Troisi, R, Aldrighetti, L, Ferrero, A, Majno, P, Toso, C, Figueras, J, Cherqui, D, Adam, R, Kokudo, N, Hasegawa, K, Guglielmi, A, Krawczyk, M, Giuliante, Felice, Hilal, Ma, Costa-Maia, J, Pinna, Ad, Cescon, M, De Santibanes, E, Urbani, L, Pawlik, T, Costa, G, Zugna, D, Clisco, Group., Vigano, L., Torzilli, G., Troisi, R., Aldrighetti, L., Ferrero, A., Majno, P., Toso, C., Figueras, J., Cherqui, D., Adam, R., Kokudo, N., Hasegawa, K., Guglielmi, A., Krawczyk, M., Giuliante, F., Hilal, M. A., Costa-Maia, J., Pinna, A. D., Cescon, M., De Santibanes, E., Urbani, L., Pawlik, T., Costa, G., Zugna, D., Vigano L., Torzilli G., Troisi R., Aldrighetti L., Ferrero A., Majno P., Toso C., Figueras J., Cherqui D., Adam R., Kokudo N., Hasegawa K., Guglielmi A., Krawczyk M., Giuliante F., Hilal M.A., Costa-Maia J., Pinna A.D., Cescon M., De Santibanes E., Urbani L., Pawlik T., Costa G., and Zugna D.

Subjects
Liver surgery, Liver Cirrhosis, Male, Cirrhosis, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Postoperative Complications, Laparotomy/methods, Medicine, liver surgery, ddc:617, Liver Cirrhosis/mortality/pathology/surgery, Liver Diseases, Middle Aged, Prognosis, Postoperative Complications/mortality/physiopathology, Treatment Outcome, 030220 oncology & carcinogenesis, classification of hepatectomie, 030211 gastroenterology & hepatology, Female, Adult, Minor Hepatectomies, Hepatectomy/adverse effects/methods, medicine.medical_specialty, classification of hepatectomies, Liver Diseases/mortality/pathology/surgery, 03 medical and health sciences, Severity of illness, overall and severe morbidity, Hepatectomy, Humans, In patient, Aged, Retrospective Studies, Analysis of Variance, Laparotomy, business.industry, Background data, liver failure, minor hepatectomy, Retrospective cohort study, bile leak, medicine.disease, Survival Analysis, Surgery, major hepatectomy, Multicenter study, Multivariate Analysis, parenchyma-sparing surgery, business, Hospitals, High-Volume
Abstract

OBJECTIVE: To elucidate minor hepatectomy (MiH) outcomes. SUMMARY BACKGROUND DATA: Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures. METHODS: We retrospectively evaluated consecutive patients who underwent open liver resections in 17 high-volume centers. EXCLUSION CRITERIA: cirrhosis and associated digestive/biliary resections. Resections were classified as (Brisbane nomenclature): limited resections (LR); (mono)segmentectomies/bisegmentectomies (Segm/Bisegm); right anterior and right posterior sectionectomies (RightAnteriorSect/RightPosteriorSect). Additionally, we defined: complex LRs (ComplexLR = LRs with exposed vessels); postero-superior segmentectomies (PosteroSuperiorSegm = segment (Sg)7, Sg8, and Sg7+Sg8 segmentectomies); and complex core hepatectomies (ComplexCoreHeps = Sg1 segmentectomies and combined resections of Sg4s+Sg8+Sg1). Left lateral sectionectomies (LLSs, n = 442) and right hepatectomies (RHs, n = 1042) were reference standards. Outcomes were adjusted for potential confounders. RESULTS: Four thousand four hundred seventy-one MiHs were analyzed. Compared with RHs, MiHs had lower 90-day mortality (0.5%/2.2%), severe morbidity (8.6%/14.4%), and liver failure rates (2.4%/11.6%, P < 0.001), but similar bile leak rates. LR and LLS had similar outcomes. ComplexLR and Segm/Bisegm of anterolateral segments had higher bile leak rates than LLS rates (OR = 2.35 and OR = 3.24), but similar severe morbidity rates. ComplexCoreHeps had higher bile leak rates than RH rates (OR = 1.94); the severe morbidity rate approached that of RH. PosteroSuperiorSegm, RightAnteriorSect, and RightPosteriorSect had severe morbidity and bile leak rates similar to RH rates. MiHs had low liver failure rates, except RightAnteriorSect (vs LLS OR = 4.02). CONCLUSIONS: MiHs had heterogeneous outcomes. Mortality was low, but MiHs could be stratified according to severe morbidity, bile leak, and liver failure rates. Some MiHs had postoperative outcomes similar to RH.

Published
2019

177. Platelets and hepatocellular cancer: Bridging the bench to the clinics

Author

Lai, aEmail Author, Q., Vitale, bEmail Author, A., Manzia, cEmail Author, T. M., Foschi, dEmail Author, F. G., Sandri, eEmail Author, G. B. L., Gambato, bEmail Author, M., Melandro, fEmail Author, F., Russo, bEmail Author, F. P., Miele, gEmail Author, L., Viganò, hEmail Author, L., Burra, bEmail Author, P., Giannini, iEmail Author, E. G., Aliberti, C., Baccarani, U., Bhoori, S., Borzio, M., Brancaccio, G., Cabibbo, G., Casadei, Gardini, Carrai, A., Cillo, P., Conti, U., Cucchetti, F., D’Ambrosio, A., Dell’Unto, R., Dematthaeis, C., Costanzo, Di, G. G., Di Sandro, S., Fucilli, F., Galati, G., Gasbarrini, A., Giuliante, F., Ghinolfi, D., Grieco, A., Gruttaduria, S., Guarino, M., Kostandini, A., Iavarone, M., Lenci, I., Losito, F., Lupo, L. G., Mazzocato, S., Mescoli, C., Miele, L., Morisco, F., Muley, M., Nicolini, D., Persico, M., Pompili, M., Ponziani, F. R., Pravisani, R., Rapaccini, G. L., Rendina, M., Renzulli, M., Rossi, M., Rreka, E., Sacco, R., Sangiovanni, A., Sessa, A., Simonetti, N., Sposito, C., Tortora, R., Trevisani, F., Viganò, M., Villa, E., Vincenzi, V., Violi, P., Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group, Lai, Q., aEmail Author, Vitale, A., bEmail Author, Manzia, T. M., cEmail Author, Foschi, F. G., dEmail Author, Sandri, G. B. L., eEmail Author, Gambato, M., bEmail Author, Melandro, F., fEmail Author, Russo, F. P., bEmail Author, Miele, L., gEmail Author, Viganò, L., hEmail Author, Burra, P., bEmail Author, Giannini, E. G., iEmail Author, Aliberti, C., Baccarani, U., Bhoori, S., Borzio, M., Brancaccio, G., Cabibbo, G., Casadei, Gardini, A., Carrai, P., Cillo, U., Conti, F., Cucchetti, A., D’Ambrosio, R., Dell’Unto, C., Dematthaei, Di, Costanzo, G., G., Di Sandro, S., Fucilli, F., Galati, G., Gasbarrini, A., Giuliante, F., Ghinolfi, D., Grieco, A., Gruttaduria, S., Guarino, M., Kostandini, A., Iavarone, M., Lenci, I., Losito, F., Lupo, L. G., Mazzocato, S., Mescoli, C., Miele, L., Morisco, F., Muley, M., Nicolini, D., Persico, M., Pompili, M., Ponziani, F. R., Pravisani, R., Rapaccini, G. L., Rendina, M., Renzulli, M., Rossi, M., Rreka, E., Sacco, R., Sangiovanni, A., Sessa, A., Simonetti, N., Sposito, C., Tortora, R., Trevisani, F., Viganò, M., Villa, E., Vincenzi, V., Violi, P., Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest, Group, Lai Q., Vitale A., Manzia T.M., Foschi F.G., Sandri G.B.L., Gambato M., Melandro F., Russo F.P., Miele L., Vigano L., Burra P., Giannini E.G., Aglitti A., Aliberti C., Baccarani U., Bhoori S., Borzio M., Brancaccio G., Cabibbo G., Casadei Gardini A., Carrai P., Cillo U., Conti F., Cucchetti A., D'ambrosio R., Dell'unto C., Dematthaeis N., Di Costanzo G.G., Di Sandro S., Fucilli F., Galati G., Gasbarrini A., Giuliante F., Ghinolfi D., Grieco A., Gruttaduria S., Guarino M., Kostandini A., Iavarone M., Lenci I., Losito F., Lupo L.G., Mazzocato S., Mescoli C., Morisco F., Muley M., Nicolini D., Persico M., Pompili M., Ponziani F.R., Pravisani R., Rapaccini G.L., Rendina M., Renzulli M., Rossi M., Rreka E., Sacco R., Sangiovanni A., Sessa A., Simonetti N., Sposito C., Tortora R., Trevisani F., Vigano M., Villa E., Vincenzi V., Violi P., Lai, Q., Vitale, A., Manzia, T. M., Foschi, F. G., Sandri, G. B. L., Gambato, M., Melandro, F., Russo, F. P., Vigano, L., Burra, P., Giannini, E. G., Casadei Gardini, A., Carrai, P., Cillo, U., Conti, F., Cucchetti, A., D'Ambrosio, R., Dell'Unto, C., Dematthaeis, N., Di Costanzo, G. G., and Vigano, M.

Subjects
Cancer Research, Integrins, Platelet-derived growth factor, Endothelium, Settore MED/12 - GASTROENTEROLOGIA, medicine.medical_treatment, Integrin, Review, lcsh:RC254-282, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Platelet-to-lymphocyte ratio, Selectins, Vascular endothelial growth factor, medicine, Platelet, Selectin, business.industry, Growth factor, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Extravasation, Settore MED/01, medicine.anatomical_structure, Oncology, chemistry, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, 030211 gastroenterology & hepatology, business
Abstract

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells' extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet-tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC. Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells’ extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet–tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC.

Published
2019

178. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma

Author

Matteo Ramazzotti, Luca Viganò, Mirella Pastore, Maria Letizia Taddei, Monika Lewinska, Javier Cibella, Clelia Peano, Erica Pranzini, Luca Di Tommaso, Elena Sacco, Jessica Iorio, Paola Chiarugi, S. Madiai, Jesper B. Andersen, Chiara Raggi, Ivan Orlandi, B. Piombanti, Giovanni Di Maira, Margherita Correnti, N. Navari, Tiziano Lottini, Annarosa Arcangeli, Giulia Lori, Claudia Campani, Fabio Marra, Raggi, C, Taddei, M, Sacco, E, Navari, N, Correnti, M, Piombanti, B, Pastore, M, Campani, C, Pranzini, E, Iorio, J, Lori, G, Lottini, T, Peano, C, Cibella, J, Lewinska, M, Andersen, J, di Tommaso, L, Vigano, L, Di Maira, G, Madiai, S, Ramazzotti, M, Orlandi, I, Arcangeli, A, Chiarugi, P, and Marra, F

Subjects
Male, 0301 basic medicine, Indoles, Carcinogenesis, Propanols, PGC-1α, Mice, SCID, Mitochondrion, Oxidative Phosphorylation, Cholangiocarcinoma, Mice, Metformin/administration & dosage, 0302 clinical medicine, Mice, Inbred NOD, Signal Transduction/drug effects, SR-18292, CCLP1, Propanols/administration & dosage, Oxidative Phosphorylation/drug effects, Electron Transport Complex II, Indoles/administration & dosage, OXPHOS, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/antagonists & inhibitors, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phenotype, Metformin, Progression-Free Survival, Mitochondria, Tumor Burden, Treatment Outcome, Neoplastic Stem Cells, 030211 gastroenterology & hepatology, Epithelial-Mesenchymal Transition/drug effects, Signal transduction, Electron Transport Complex II/metabolism, Tumor Burden/drug effects, Signal Transduction, Epithelial-Mesenchymal Transition, Oxidative phosphorylation, Biology, Transfection, 03 medical and health sciences, HUCCT1, Neoplastic Stem Cells/metabolism, Cancer stem cell, Cell Line, Tumor, Mitochondria/metabolism, Cholangiocarcinoma/drug therapy, Animals, Humans, Gene silencing, Gene Silencing, Hepatology, Bile Duct Neoplasms/drug therapy, Carcinogenesis/drug effects, Xenograft Model Antitumor Assays, Embryonic stem cell, 030104 developmental biology, Bile Duct Neoplasms, Mitochondrial biogenesis, Cancer research
Abstract

BACKGROUND & AIMS: Little is known about the metabolic regulation of cancer stem cells (CSCs) in cholangiocarcinoma (CCA). We analyzed whether mitochondrial-dependent metabolism and related signaling pathways contribute to stemness in CCA.METHODS: The stem-like subset was enriched by sphere culture (SPH) in human intrahepatic CCA cells (HUCCT1 and CCLP1) and compared to cells cultured in monolayer. Extracellular flux analysis was examined by Seahorse technology and high-resolution respirometry. In patients with CCA, expression of factors related to mitochondrial metabolism was analyzed for possible correlation with clinical parameters.RESULTS: Metabolic analyses revealed a more efficient respiratory phenotype in CCA-SPH than in monolayers, due to mitochondrial oxidative phosphorylation. CCA-SPH showed high mitochondrial membrane potential and elevated mitochondrial mass, and over-expressed peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, a master regulator of mitochondrial biogenesis. Targeting mitochondrial complex I in CCA-SPH using metformin, or PGC-1α silencing or pharmacologic inhibition (SR-18292), impaired spherogenicity and expression of markers related to the CSC phenotype, pluripotency, and epithelial-mesenchymal transition. In mice with tumor xenografts generated by injection of CCA-SPH, administration of metformin or SR-18292 significantly reduced tumor growth and determined a phenotype more similar to tumors originated from cells grown in monolayer. In patients with CCA, expression of PGC-1α correlated with expression of mitochondrial complex II and of stem-like genes. Patients with higher PGC-1α expression by immunostaining had lower overall and progression-free survival, increased angioinvasion and faster recurrence. In GSEA analysis, patients with CCA and high levels of mitochondrial complex II had shorter overall survival and time to recurrence.CONCLUSIONS: The CCA stem-subset has a more efficient respiratory phenotype and depends on mitochondrial oxidative metabolism and PGC-1α to maintain CSC features.LAY SUMMARY: The growth of many cancers is sustained by a specific type of cells with more embryonic characteristics, termed 'cancer stem cells'. These cells have been described in cholangiocarcinoma, a type of liver cancer with poor prognosis and limited therapeutic approaches. We demonstrate that cancer stem cells in cholangiocarcinoma have different metabolic features, and use mitochondria, an organelle located within the cells, as the major source of energy. We also identify PGC-1α, a molecule which regulates the biology of mitochondria, as a possible new target to be explored for developing new treatments for cholangiocarcinoma.

Published
2021
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179. Stratification of Major Hepatectomies According to Their Outcome

Author

Viganò, Luca, Torzilli, Guido, Aldrighetti, Luca, Ferrero, Alessandro, Troisi, Roberto, Figueras, Joan, Cherqui, Daniel, Adam, René, Kokudo, Norihiro, Hasegawa, Kiyoshi, Guglielmi, Alfredo, Majno, Pietro, Toso, Christian, Krawczyk, Marek, Abu Hilal, Mohammad, Pinna, Antonio Daniele, Cescon, Matteo, Giuliante, Felice, De Santibanes, Eduardo, Costa-Maia, José, Pawlik, Timothy, Urbani, Lucio, Zugna, Daniela, CLISCO group, Vigano, L., Torzilli, G., Aldrighetti, L., Ferrero, A., Troisi, R., Figueras, J., Cherqui, D., Adam, R., Kokudo, N., Hasegawa, K., Guglielmi, A., Majno, P., Toso, C., Krawczyk, M., Abu Hilal, M., Pinna, A. D., Cescon, M., Giuliante, F., De Santibanes, E., Costa-Maia, J., Pawlik, T., Urbani, L., and Zugna, D.

Subjects
Liver Cirrhosis, Male, Cirrhosis, medicine.medical_treatment, Outcome analysis, Stratification (mathematics), 0302 clinical medicine, liver surgery, extended hepatectomy, Right hepatectomy, ddc:617, Liver Diseases, Liver Neoplasms, Confounding, Middle Aged, postoperative mortality, Outcome and Process Assessment, Health Care, Classification of hepatectomies, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, medicine.medical_specialty, Major hepatectomy, right hepatectomy, MEDLINE, classification of hepatectomies, Outcome and Process Assessment, 03 medical and health sciences, Text mining, medicine, Hepatectomy, Humans, Bile leak, bile leak, liver failure, major hepatectomy, severe morbidity, Aged, Retrospective Studies, In patient, Liver surgery, Postoperative mortality, business.industry, General surgery, Liver failure, Retrospective cohort study, Odds ratio, medicine.disease, Surgery, Health Care, Extended hepatectomy, Severe morbidity, Liver function, business
Abstract

Objective To stratify major hepatectomies (MajHs) according to their outcomes. Summary of background data MajHs are associated with non-negligible operative risks, but they include a wide range of procedures. Detailed depiction of the outcomes of different MajHs is the basis for a new classification of liver resections. Methods We retrospectively considered patients that underwent hepatectomy in 17 high-volume centers. Patients with an associated digestive/biliary resection were excluded. We analyzed open MajHs in non-cirrhotic patients. MajHs were classified according to the Brisbane nomenclature. Right hepatectomies (RHs) were reference standards. Outcomes were adjusted for potential confounders, including indication, liver function, preoperative portal vein embolization, and enrolling center. Results We analyzed a series of 2212 patients. In comparison with RH, left hepatectomy had lower mortality [0.6% vs 2.2%, odds ratio (OR) = 0.25], severe morbidity (11.7% vs 14.4%, OR = 0.62), and liver failure rates (2.1% vs 11.6%, OR = 0.16). Left hepatectomy+Sg1 and mesohepatectomy+/-Sg1 had outcomes similar to RH, except for higher bile leak rate (31.3% and 13.5% vs 6.7%, OR = 4.36 and OR = 2.29). RH + Sg1 had slightly worse outcomes than RH. Right and left trisectionectomies had higher mortality (5.0% and 7.3% vs 2.2%, OR = 2.07 and OR = 2.71) and liver failure rates than RH (19.0% and 22.0% vs 11.6%, OR = 2.03 and OR = 2.21). Left trisectionectomy had even higher severe morbidity (25.6% vs 14.4%, OR = 2.07) and bile leak rates (14.6% vs 6.7%, OR = 2.31). Conclusions The term "major hepatectomy" includes resections having heterogeneous outcome. Different MajHs can be stratified according to their mortality, severe morbidity, liver failure, and bile leak rates.

Published
2020
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180. Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma

Author

Andrea Fontana, Daniele Antonio Pinna, Giorgio Ercolani, Giulia Isa, Luca Viganò, Guido Torzilli, Simone Conci, Andrea Ruzzenente, Eduardo de Santibañes, Esteban Gonzalez, Alfredo Guglielmi, Tommaso Campagnaro, Calogero Iacono, Claudia Salaris, Corrado Pedrazzani, Fabio Bagante, Conci S., Vigano L., Ercolani G., Gonzalez E., Ruzzenente A., Isa G., Salaris C., Fontana A., Bagante F., Pedrazzani C., Campagnaro T., Iacono C., De Santibanes E., Pinna D.A., Torzilli G., and Guglielmi A.

Subjects
Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Portal vein, Vena Cava, Inferior, Inferior vena cava, Cholangiocarcinoma, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Hepatectomy, Humans, Neoplasm Invasiveness, Mortality, Vascular resection, Liver surgery, Intrahepatic Cholangiocarcinoma, Aged, Proportional Hazards Models, Intrahepatic cholangiocarcinoma, Curative intent, business.industry, Margins of Excision, Hepatic nodules, General Medicine, Middle Aged, Neoadjuvant Therapy, Surgery, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Oncology, medicine.vein, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Multivariate Analysis, Lymph Node Excision, Biliary tract cancer, Female, 030211 gastroenterology & hepatology, Lymph Nodes, business, Vascular Surgical Procedures
Abstract

Background and aims We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival. Results Thirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p Conclusion Vascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).

Published
2020
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183. Role of Lymph Node Dissection in Small (≤ 3 cm) Intrahepatic Cholangiocarcinoma

Author

Calogero Iacono, G. Torzilli, Serena Manfreda, Alfredo Guglielmi, Fabio Bagante, Simone Conci, Andrea Ruzzenente, Luca Viganò, Corrado Pedrazzani, Giorgio Ercolani, Antonio D Pinna, Andrea Ciangherotti, Ruzzenente A., Conci S., Vigano L., Ercolani G., Manfreda S., Bagante F., Ciangherotti A., Pedrazzani C., Pinna A.D., Iacono C., Torzilli G., and Guglielmi A.

Subjects
Male, medicine.medical_specialty, Lymph node dissection, Gastroenterology, Metastasis, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, In patient, Liver surgery, Surgical treatment, Lymph node, Intrahepatic Cholangiocarcinoma, Aged, Retrospective Studies, Tumor size, business.industry, Incidence (epidemiology), medicine.disease, Tumor Burden, Survival Rate, Dissection, Bile Ducts, Intrahepatic, medicine.anatomical_structure, Bile Duct Neoplasms, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Lymph Node Excision, Female, 030211 gastroenterology & hepatology, Surgery, business
Abstract

Background and Aims: The role of lymph node dissection (LND) in patients with small intrahepatic cholangiocarcinoma (ICC) is still under debate. The aims of this study were to compare the lymph node (LN) status and its correlation with survival among patients with ICC stratified by tumor size. Methods: A retrospective analysis of a multi-institutional series of 259 patients undergoing curative-intent surgery was carried out. Patients were stratified into Small-ICC (≤ 3cm) and Large-ICC (> 3cm) based on tumor size. Results: There were 53 and 206 patients in Small-ICC and Large-ICC groups, respectively. The incidence of LND was 62% among Small-ICC patients and 78% among Large-ICC patients (p = 0.016). LN metastases were identified in 30.3% and 38.5% of Small-ICC and Large-ICC patients, respectively (p = 0.37). No differences in terms of number of harvested LN and LN metastases were identified comparing Small- and Large-ICC patients. The 5-year overall survival (OS) was 52.6% for Small-ICC and 36.2% for Large-ICC (p = 0.024). The 5-year OS according to the LN status (N0 vs N+) was 84.8% and 36.0% (p = 0.032) in Small-ICC, and 45.7% and 12.1% in Large-ICC (p < 0.001), respectively. Conclusion: While Small-ICC patients with no LN metastasis had a good long-term survival, the LN resulted in an important variable associated with survival also for patients in this group. Moreover, the incidence of LN metastasis did not differ when comparing Small-ICC and Large-ICC patients, suggesting that LND is mandatory in the surgical treatment of ICC regardless of tumor size.

Published
2019

184. The Influence of Aging on Hepatic Regeneration and Early Outcome after Portal Vein Occlusion: A Case-Control Study

Author

Federica Cipriani, Luca Aldrighetti, Nadia Russolillo, Luca Viganò, Alessandro Ferrero, Francesca Ratti, Serena Langella, Russolillo, N, Ratti, F, Vigano, L, Langella, S, Cipriani, F, Aldrighetti, L, and Ferrero, A

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Aging, Organoplatinum Compounds, medicine.medical_treatment, Portal vein, Irinotecan, Preoperative care, Diabetes Complications, Young Adult, Sex Factors, Occlusion, Antineoplastic Combined Chemotherapy Protocols, Preoperative Care, medicine, Hepatectomy, Humans, Young adult, Aged, Aged, 80 and over, business.industry, Portal Vein, Regeneration (biology), Liver Neoplasms, Case-control study, Age Factors, Organ Size, Middle Aged, Embolization, Therapeutic, Liver regeneration, Neoadjuvant Therapy, Surgery, Liver Regeneration, Bevacizumab, Oxaliplatin, Radiography, Biliary Tract Neoplasms, Oncology, Liver, Chemotherapy, Adjuvant, Case-Control Studies, Camptothecin, Female, Fluorouracil, business
Abstract

Portal vein occlusion (PVO) is used to increase inadequate future liver remnant volume (FLRV). Impaired liver regeneration has been reported in aged animals. This study was designed to evaluate the impact of patient age on hepatic regeneration. Sixty patients aged a parts per thousand yen70 years were matched 1:1 with 60 patients aged < 70 years. Matching criteria were sex, diabetes, cirrhosis, pre-PVO chemotherapy and bevacizumab administration, and jaundice. The median ages in the older and younger groups were 76 (range 70-83) years and 59 (range 20-69) years, respectively (p < 0.001). Median FLRV following PVO (33.1 +/- A 6.8 vs. 31.9 +/- A 6.0 %) and volumetric increase (0.52 +/- A 0.35 vs. 0.49 +/- A 0.34) were similar in the two groups. Of the older and younger patients, 10 % and 1.7 %, respectively, did not undergo liver surgery after PVO (p = 0.051). Mortality (5.5 vs. 6.7 %) and major morbidity (25.9.8 vs. 22 %) rates were similar. Liver failure rate was higher in older patients (35.1 vs. 16.9 %, p < 0.026), mainly due to Grade A liver failure (20.3 vs. 8.4 %, p < 0.001). Multivariate analysis showed that age a parts per thousand yen 70 years [odds ratio (OR) 3.03; 95 % confidence interval (CI) 1.18-7.78; p = 0.020] and biliary cancer diagnosis (OR 4.69; 95 % CI 1.81-12.09; p = 0.001) were independent risk factors for postoperative liver failure. Liver regeneration after PVO is not impaired by age. Nevertheless, liver resection in elderly patients is performed less often after PVO and carries a higher risk of liver failure.

Published
2014

185. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery

Author

Luisa Pascucci, Eugenio Parati, Lucia Viganò, Giulio Alessandri, Piero Ceccarelli, Maria Ester Bernardo, Gianpietro Bondiolotti, Maurizio Muraca, Silvia Maria Doglia, Augusto Pessina, Arianna Bonomi, Valentina Coccè, Emilio Ciusani, Francesca Sisto, Alberta Locatelli, Diletta Ami, Pascucci, L, Coccè, V, Bonomi, A, Ami, D, Ceccarelli, P, Ciusani, E, Viganò, L, Locatelli, A, Sisto, F, Doglia, S, Parati, E, Bernardo, M, Muraca, M, Alessandri, G, Bondiolotti, G, Pessina, A, Pascucci, L., Cocce, V., Bonomi, A., Ami, D., Ceccarelli, P., Ciusani, E., Vigano, L., Locatelli, A., Sisto, F., Doglia, S. M., Parati, E., Bernardo, M. E., Muraca, M., Alessandri, G., Bondiolotti, G., and Pessina, A.

Subjects
BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Paclitaxel, Mesenchymal stromal cells, Exosome, Microvesicles, Drug delivery, Pharmaceutical Science, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Antineoplastic Agents, Exosomes, Cell Line, Antineoplastic Agent, chemistry.chemical_compound, Mice, Drug Delivery Systems, Microvesicle, Neoplasms, Cell Line, Tumor, Animals, Humans, Secretion, Tumor microenvironment, Mesenchymal Stromal Cell, Animal, Mesenchymal stem cell, Mesenchymal Stem Cells, In vitro, Cell biology, chemistry, Cell culture, Immunology, Neoplasm, Drug Delivery System, Human
Abstract

Mesenchymal stromal cells (MSCs) have been proposed for delivering anticancer agents because of their ability to home in on tumor microenvironment. We found that MSCs can acquire strong anti-tumor activity after priming with Paclitaxel (PTX) through their capacity to uptake and then release the drug. Because MSCs secrete a high amount of membrane microvesicles (MVs), we here investigated the role of MVs in the releasing mechanism of PTX. The murine SR4987 line was used as MSC model. The release of PTX from SR4987 in the conditioned medium (CM) was checked by HPLC and the anti-tumor activity of both CM and MVs was tested on the human pancreatic cell line CFPAC-1. MVs were isolated by ultracentrifugation, analyzed by transmission (TEM) and scanning electron microscopy (SEM), and the presence of PTX by the Fourier transformed infrared (FTIR) microspectroscopy. SR4987 loaded with PTX (SR4987PTX) secreted a significant amount of PTX and their CM possessed strong anti-proliferative activity on CFPAC-1. At TEM and SEM, SR4987PTX showed an increased number of "vacuole-like" structures and shed a relevant number of MVs, but did not differ from untreated SR4987. However, SR4987PTX-derived-MVs (SR4987PTX-MVs) demonstrated a strong anti proliferative activity on CFPAC-1. FTIR analysis of SR4987PTX-MVs showed the presence of an absorption spectrum in the corresponding regions of the PTX marker, absent in MVs from SR4987. Our work is the first demonstration that MSCs are able to package and deliver active drugs through their MVs, suggesting the possibility of using MSCs as a factory to develop drugs with a higher cell-target specificity. © 2014 Elsevier B.V.

Published
2014

186. Towards a Standardization of Learning Curve Assessment in Minimally Invasive Liver Surgery.

Author

Kuemmerli C, Toti JMA, Haak F, Billeter AT, Nickel F, Guidetti C, Santibanes M, Vigano L, Lavanchy JL, Kollmar O, Seehofer D, Abu Hilal M, Di Benedetto F, Clavien PA, Dutkowski P, Müller BP, and Müller PC

Abstract

Objective: The aim was to analyze the learning curves of minimal invasive liver surgery(MILS) and propose a standardized reporting., Summary Background Data: MILS offers benefits compared to open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization., Methods: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves, and characterization of different learning phases(competency, proficiency and mastery)., Results: 60 articles with 12'241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42) and postoperative complications (n=38). Overall competency, proficiency and mastery were reached after 34 (IQR 19-56), 50 (IQR 24-74), 58 (IQR 24-100) procedures respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: -13%, 2%; blood loss: competency to proficiency to mastery: -33%, 0%; conversion rate (competency to proficiency to mastery; -21%, -29%), whereas postoperative complications improved later (competency to proficiency to mastery: -25%, -41%)., Conclusions: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized three-phase reporting of learning phases (competency, proficiency, mastery) is proposed and should be followed., Competing Interests: Compliance with Ethical Standards: Conflict of interest: The authors declare that they have no conflict of interest. Conflict of interest: The authors declare no conflict of interest. No grants and financial support were received for this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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187. Distant supervision for imaging-based cancer sub-typing in Intrahepatic Cholangiocarcinoma.

Author

Savino MS, Cavinato L, Costa G, Fiz F, Torzilli G, Vigano L, and Ieva F

Subjects
Bile Ducts, Intrahepatic pathology, Diagnostic Imaging, Humans, Reproducibility of Results, Bile Duct Neoplasms diagnostic imaging, Bile Duct Neoplasms genetics, Cholangiocarcinoma diagnostic imaging, Cholangiocarcinoma genetics
Abstract

Finding effective ways to perform cancer sub-typing is currently a trending research topic for therapy opti-mization and personalized medicine. Stemming from genomic field, several algorithms have been proposed. In the context of texture analysis, limited efforts have been attempted, yet imaging information is known to entail useful knowledge for clinical practice. We propose a distant supervision model for imaging-based cancer sub-typing in Intrahepatic Cholangiocar-cinoma patients. A clinically informed stratification of patients is built and homogeneous groups of patients are characterized in terms of survival probabilities, qualitative cancer variables and radiomic feature description. Moreover, the contributions of the information derived from the ICC area and from the peri tumoral area are evaluated. The findings suggest the reliability of the proposed model in the context of cancer research and testify the importance of accounting for data coming from both the tumour and the tumour-tissue interface. Clinical relevance - In order to accurately predict cancer prognosis for patients affected by ICC, radiomic variables of both core cancer and surrounding area should be exploited and employed in a model able to manage complex information.

Published
2022
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189. Microvilli Adhesion: An Alternative Route for Nanoparticle Cell Internalization.

Author

Sommi P, Vitali A, Coniglio S, Callegari D, Barbieri S, Casu A, Falqui A, Vigano' L, Vigani B, Ferrari F, and Anselmi-Tamburini U

Subjects
Biological Transport, Endocytosis, Microvilli, Nanomedicine, Nanoparticles
Abstract

The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated. This microvillus-mediated adhesion (MMA) has been observed using ceria and magnetite NPs with a dimension of <40 nm functionalized with polyacrylic acid but not using NPs with a neutral or positive functionalization. Such an adhesion was not cell specific, as it was demonstrated in three different cell lines. MMA was also reduced by modifications of the microvillus lipid rafts, obtained by depleting cholesterol and altering synthesis of sphingolipids. We found a direct relationship between MAA, cell cycle, and density of microvilli. The evidence suggests that MMA differs from the commonly described uptake mechanisms and might represent an interesting alternative approach for selective NP delivery.

Published
2021
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191. Percutaneous ablation of post-surgical solitary early recurrence of colorectal liver metastases is an effective "test-of-time" approach.

Author

Vigano L, Galvanin J, Poretti D, Del Fabbro D, Gentile D, Pedicini V, Solbiati L, and Torzilli G

Subjects
Hepatectomy, Humans, Neoplasm Recurrence, Local, Treatment Outcome, Catheter Ablation, Colorectal Neoplasms surgery, Liver Neoplasms surgery
Abstract

Standard treatment of early recurrence of colorectal liver metastases (CLM) after liver resection (LR) is chemotherapy followed by loco-regional therapy. We reviewed the outcome of a different strategy ("test-of-time" approach): upfront percutaneous ablation without chemotherapy. Twenty-six consecutive patients with early solitary liver-only recurrence amenable to both resection and ablation (< 30 mm, distant from vessels) undergone "test-of-time" approach were analyzed. Early recurrence had a median size of 17 mm and occurred after a median interval from LR of 4 months. Primary efficacy rate of ablation was 100%. Five patients are alive and disease-free after a mean follow-up of 46 months. Five patients had local-only recurrence; all had repeat treatment (LR = 4; Ablation = 1) without chemotherapy. Local recurrence risk was associated with incomplete ablation of 1-cm thick peritumoral margin. The remaining 16 patients had non-local recurrence, 13 early after ablation. Overall, six (23%) patients had ablation as unique treatment and 13 (50%) avoided or postponed chemotherapy (mean chemotherapy-free interval 33.5 months). Ablation without chemotherapy of early liver-only recurrence is a reliable "test-of-time" approach. It minimized the invasiveness of treatment with good effectiveness and high salvageability in case of local failure, avoided worthless surgery, and saved chemotherapy for further disease progression., (© 2021. Italian Society of Surgery (SIC).)

Published
2021
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192. Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites.

Author

Vigano L, Corleone P, Darwish SS, Turri N, Famularo S, Viggiani L, Rimassa L, Del Fabbro D, Di Tommaso L, and Torzilli G

Abstract

Background: Systemic therapy is the standard treatment for patients with hepatic and extrahepatic colorectal metastases. It is assumed to have the same effectiveness on all disease foci, independent of the involved organ. The present study aims to compare the response rates of hepatic and extrahepatic metastases to systemic therapy., Methods: All consecutive patients undergoing simultaneous resection of hepatic and extrahepatic metastases from colorectal cancer after oxaliplatin- and/or irinotecan-based preoperative chemotherapy were analyzed. All specimens were reviewed. Pathological response to chemotherapy was classified according to tumor regression grade (TRG)., Results: We analyzed 45 patients undergoing resection of 134 hepatic and 72 extrahepatic metastases. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4-5 95% and 100% vs. 67%, p = 0.008, and p = 0.006). Peritoneal metastases had a higher pathological response rate than liver metastases (TRG 1-3 66% vs. 33%, p < 0.001) and non-hepatic non-peritoneal metastases (3%, p < 0.001). Metastases site was an independent predictor of pathological response to systemic therapy., Conclusions: Response to chemotherapy of distant metastases from colorectal cancer varies in different organs. Systemic treatment is highly effective for peritoneal metastases, more so than liver metastases, while it has a very poor impact on lung and lymph node metastases.

Published
2021
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193. The role of left fronto-parietal tracts in hand selection: Evidence from neurosurgery.

Author

Howells H, Puglisi G, Leonetti A, Vigano L, Fornia L, Simone L, Forkel SJ, Rossi M, Riva M, Cerri G, and Bello L

Subjects
Diffusion Tensor Imaging, Humans, Nerve Net, Neural Pathways, Neurosurgical Procedures, Neurosurgery, White Matter diagnostic imaging
Abstract

Strong right-hand preference on the population level is a uniquely human feature, although its neural basis is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. An atlas-based disconnectome analysis was conducted to evaluate whether resection of tracts was significantly associated with changes in hand selection. Diffusion tractography was also used to dissect fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with frontal and parietal resections rather than other lobes. In particular, the shift in hand selection was significantly associated with the resection of dorsal rather than ventral fronto-parietal white matter connections. Dorsal white matter pathways contribute bilaterally to control of goal-directed hand movements. We show that unilateral lesions, that may unbalance the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2020
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194. Tumor-Infiltrating Lymphocytes and Macrophages in Intrahepatic Cholangiocellular Carcinoma. Impact on Prognosis after Complete Surgery.

Author

Vigano L, Soldani C, Franceschini B, Cimino M, Lleo A, Donadon M, Roncalli M, Aghemo A, Di Tommaso L, and Torzilli G

Subjects
Aged, Bile Duct Neoplasms pathology, Bile Ducts, Intrahepatic pathology, Cholangiocarcinoma mortality, Cholangiocarcinoma pathology, Female, Humans, Italy epidemiology, Leukocyte Count, Lymphocytes, Tumor-Infiltrating immunology, Male, Postoperative Period, Prognosis, Survival Rate trends, Bile Duct Neoplasms surgery, Bile Ducts, Intrahepatic surgery, Cholangiocarcinoma surgery, Hepatectomy, Immunity, Cellular, Lymphocytes, Tumor-Infiltrating pathology, Macrophages pathology
Abstract

Background: Immune infiltrate impacts prognosis of several tumors. To assess the prognostic impact of tumor-infiltrating lymphocytes and macrophages in patients undergoing resection for intrahepatic cholangiocellular carcinoma (ICC)., Methods: All consecutive patients undergoing surgery for ICC between 2008 and 2016 were considered. Inclusion criteria were complete resection and follow-up > 12 months. Tissue sections were immunostained for CD3+, CD4+, CD8+, Foxp3+, and CD68+. The number of positive cells was quantified using a computer-aided image analysis system. Different cut-off values were tested as predictors of overall survival (OS)., Results: Fifty-three patients were analyzed. ICC were T1 in 28 patients, multifocal in 11, and N+ in 13. After a median follow-up of 42 months, 5-year OS was 52.1%. The following immune infiltrate values were associated with better OS: CD3+ > 0.10% (5-year OS 63.3% vs. 13.6% if ≤ 0.10%, p = 0.001); CD8+ > 0.10% (56.2% vs. 28.6% if ≤ 0.10%, p = 0.051); Foxp3+ absent (59.4% vs. 16.0% if present, p = 0.049). CD4+ and CD68+ infiltrates were not associated with OS. Three-year OS rates in patients with 0, 1, and ≥ 2 negative prognostic factors were 73.6%, 47.3%, and 14.3%, respectively (p < 0.001). CD3+ infiltrate stratified prognosis in T1 tumors (3-year OS 71.7% if CD3+ > 0.10% vs. 14.3% if ≤ 0.10%, p < 0.001)., Conclusions: Tumor-infiltrating lymphocytes are associated with prognosis of ICC patients after complete surgery. CD3+ and CD8+ infiltrate is associated with higher survival and lower recurrence risk, while Foxp3+ infiltrate is associated with worse prognosis. CD3+ infiltrate allows refining prediction of prognosis in early tumors.

Published
2019
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195. BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

Author

Bachet JB, Moreno-Lopez N, Vigano L, Marchese U, Gelli M, Raoux L, Truant S, Laurent C, Herrero A, Le Roy B, Deguelte Lardiere S, Passot G, Hautefeuille V, De La Fouchardiere C, Artru P, Ameto T, Mabrut JY, Schwarz L, Rousseau B, Lepère C, Coriat R, Brouquet A, Sa Cunha A, and Benoist S

Subjects
Aged, Case-Control Studies, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, Disease-Free Survival, Female, Hepatectomy, Humans, Liver Neoplasms genetics, Liver Neoplasms mortality, Liver Neoplasms surgery, Male, Middle Aged, Mutation genetics, Survival Analysis, Colorectal Neoplasms genetics, Liver Neoplasms secondary, Neoplasm Recurrence, Local genetics, Proto-Oncogene Proteins B-raf genetics
Abstract

Background: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs., Methods: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval., Results: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034)., Conclusion: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer., (© 2019 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Published
2019
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197. Prospective Evaluation of Intrahepatic Microscopic Occult Tumor Foci in Patients with Numerous Colorectal Liver Metastases.

Author

Vigano L, Di Tommaso L, Mimmo A, Sollai M, Cimino M, Donadon M, Roncalli M, and Torzilli G

Subjects
Aged, Female, Humans, Liver Neoplasms diagnostic imaging, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Risk Factors, Tomography, X-Ray Computed, Colorectal Neoplasms pathology, Liver Neoplasms secondary, Liver Neoplasms surgery, Neoplasm Recurrence, Local pathology
Abstract

Background: Patients with numerous colorectal liver metastases (CLM) have high risk of early recurrence after liver resection (LR). The presence of intrahepatic occult microscopic metastases missed by imaging has been hypothesized, but it has never been assessed by pathology analyses., Methods: All patients with > 10 CLM who underwent LR between September 2015 and September 2016 were considered. A large sample of liver without evidence of disease ("healthy liver") was taken from the resected specimen and sent to the pathologist. One mm-thick sections were analyzed. Any metastasis, undetected by preoperative and intraoperative imaging, but identified by the pathologist was classified as occult microscopic metastasis., Results: Ten patients were prospectively enrolled (median number of CLM n = 15). In a per-lesion analysis, the sensitivity of computed tomography and magnetic resonance imaging was 91 and 98% respectively. The pathology examination confirmed all the CLM. All patients had an adequate sample of "healthy liver" (median number of examined blocks per sample n = 14 [5-33]). No occult microscopic metastases were detected. After a median follow-up of 15 months, 5 patients were disease-free. Recurrence was hepatic and bilobar in all patients., Conclusions: Clinically relevant occult microscopic disease in patients with numerous CLM is excluded. These results support the indication to resection in such patients and exclude the need for de principe major hepatectomy to increase the completeness of surgery., (© 2018 S. Karger AG, Basel.)

Published
2019
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198. Progression of Colorectal Liver Metastases from the End of Chemotherapy to Resection: A New Contraindication to Surgery?

Author

Vigano L, Darwish SS, Rimassa L, Cimino M, Carnaghi C, Donadon M, Procopio F, Personeni N, Del Fabbro D, Santoro A, and Torzilli G

Subjects
Adult, Aged, Bevacizumab administration & dosage, Contraindications, Procedure, Disease-Free Survival, Female, Fluorouracil administration & dosage, Hepatectomy, Humans, Irinotecan administration & dosage, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology, Liver Neoplasms secondary, Magnetic Resonance Imaging, Male, Middle Aged, Oxaliplatin administration & dosage, Response Evaluation Criteria in Solid Tumors, Risk Factors, Survival Rate, Tomography, X-Ray Computed, Tumor Burden, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms pathology, Disease Progression, Liver Neoplasms therapy
Abstract

Background: Not all patients with resectable colorectal liver metastases (CLM) benefit from liver resection (LR); only patients with disease progression during chemotherapy are excluded from surgery., Objective: This study was performed to determine whether tumor behavior (stable disease/progression) from the end of chemotherapy to LR impacts prognosis., Methods: Patients undergoing LR after tumor response or stabilization during chemotherapy were considered. Overall, 128 patients who underwent examination by two imaging modalities (computed tomography/magnetic resonance imaging) after chemotherapy with a > 3-week interval between the two imaging modalities were analyzed. Any variation in CLM size was registered. Tumor progression was defined according to the response evaluation criteria in solid tumors (RECIST) criteria., Results: Among 128 patients with stable disease or partial response to preoperative chemotherapy, 32 (25%) developed disease progression in the chemotherapy to LR interval, with a disease progression rate of 17% when this interval was < 8 weeks. Survival was lower among patients with progression than those with stable disease [3-year overall survival (OS) 23.0 vs. 52.4%, and recurrence-free survival (RFS) 6.3% vs. 21.6%; p < 0.001]. Survival was extremely poor in patients with early progression (< 8 weeks) (0.0% 2-year OS, 12.5% 6-month RFS). Disease progression in the chemotherapy to LR interval was an independent negative prognostic factor for OS and RFS [hazard ratio 3.144 and 2.350, respectively; p < 0.001]., Conclusions: Early disease progression in the chemotherapy to LR interval occurred in approximately 15% of patients and was associated with extremely poor survival. Even if these data require validation, the risk for early disease progression after chemotherapy should be considered, and, if progression is evident, the indication for surgery should be cautiously evaluated.

Published
2018
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199. Reversibility of chemotherapy-related liver injury.

Author

Vigano L, De Rosa G, Toso C, Andres A, Ferrero A, Roth A, Sperti E, Majno P, and Rubbia-Brandt L

Subjects
Adult, Aged, Aged, 80 and over, Female, Hepatectomy, Humans, Liver Neoplasms surgery, Male, Middle Aged, Retrospective Studies, Antineoplastic Agents adverse effects, Chemical and Drug Induced Liver Injury therapy, Colorectal Neoplasms pathology, Liver Neoplasms drug therapy, Liver Neoplasms secondary
Abstract

Background & Aims: Chemotherapy-associated liver injury (CALI) increases the risk of liver resection and may prejudice further surgery and chemotherapy. The reversibility of CALI is therefore important; however, no data concerning this are available. This study aimed to retrospectively analyze the reversibility of CALI in patients undergoing liver resection for colorectal metastases., Methods: All resections of colorectal liver metastases after oxaliplatin and/or irinotecan-based chemotherapy were included. First, liver resections were stratified by time between end of chemotherapy and hepatectomy and several possible cut-off values tested. CALI prevalence in various groups was compared. Second, CALI in the two specimens from each patient who had undergone repeat liver resections without interval chemotherapy were compared., Results: Overall, 524 liver resections in 429 patients were analyzed. The median interval chemotherapy-surgery was 56days (15-1264). CALI prevalence did not differ significantly between groups with a chemotherapy-surgery interval <270days. Grade 2-3 sinusoidal dilatation (SOS, 19.4% vs. 40.0%, p=0.022) and nodular regenerative hyperplasia (NRH, 6.5% vs. 20.1%, p=0.063) occurred less frequently in patients with an interval >270days (n=31); prevalence of steatosis and steatohepatitis was similar in all groups. A chemotherapy-surgery interval >270days was an independent protector against Grade 2-3 SOS (p=0.009). Forty-seven patients had repeat liver resection without interval chemotherapy. CALI differed between surgeries only for a chemotherapy-surgery interval >270days (n=15), Grade 2-3 SOS having regressed in 4/5 patients and NRH in 7/8; whereas steatosis and steatohepatitis had persisted., Conclusions: CALI persists for a long time after chemotherapy. SOS and NRH regress only after nine months without chemotherapy, whereas steatosis and steatohepatitis persist., Lay Summary: The patients affected by colorectal liver metastases often receive chemotherapy before liver resection, but chemotherapy causes liver injuries that may increase operative risks and reduce tolerance to further chemotherapy. The authors analyzed the reversibility of the liver injuries after the chemotherapy interruption. Liver injuries persist for a long time after chemotherapy. Sinusoidal dilatation and nodular regenerative hyperplasia regress only nine months after the end of chemotherapy, whereas steatosis and steatohepatitis persist even after this long interval., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2017
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200. Laparoscopic simultaneous resection of colorectal primary tumor and liver metastases: a propensity score matching analysis.

Author

Tranchart H, Fuks D, Vigano L, Ferretti S, Paye F, Wakabayashi G, Ferrero A, Gayet B, and Dagher I

Subjects
Adult, Aged, Blood Loss, Surgical, Blood Transfusion, Databases, Factual, Female, Humans, Male, Matched-Pair Analysis, Middle Aged, Operative Time, Propensity Score, Survival Analysis, Colorectal Neoplasms surgery, Hepatectomy methods, Laparoscopy methods, Liver Neoplasms secondary, Liver Neoplasms surgery
Abstract

Background: Preliminary series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). The aim of this study was to compare the short- and long-term outcomes for matched patients undergoing combined resections., Methods: An international multicenter database of 142 patients that underwent combined laparoscopic resection of CRC and SCRLM between 1997 and 2013 was compared to a database of 241 patients treated by open during the same period. Comparison of short- and long-term outcomes was performed after propensity score adjustment., Results: After matching, 89 patients were compared in each group including mostly ASA I-II patients, presenting with mean number of 1.5 CRLM, with a mean diameter of 30 mm, and resectable by a wedge resection or a left lateral sectionectomy. A rectal resection was required in 46 and 43 % of laparoscopic and open procedures, respectively (p = 0.65). There was no difference in global operative time, blood loss and transfusion rates between the two groups. A conversion was required in 7 % of the laparoscopic procedures. Morbidity rates were similar in the two groups (p = 1.0). The 3-year overall survival in the laparoscopy and open groups were 78 and 65 %, respectively (p = 0.17)., Conclusions: In patients without severe comorbidities presenting with one, small (≤3 cm), CRLM resectable by a wedge resection or a left lateral sectionectomy, combined laparoscopic resection of CRC and SCRLM allowed similar short- and long-term outcomes compared with the open approach.

Published
2016
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