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Irreversible electroporation for the management of pancreatic cancer: Current data and future directions

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World Journal of Gastroenterology 2023年第2期29卷 223-231页

作者： Stavros Spiliopoulos Lazaros Reppas Dimitrios Filippiadis antonella delvecchio Maria Conticchio Riccar do Memeo Riccardo Inchingolo Second Department of Radiology School of MedicineNational and Kapodistrian University of AthensAthens 12461AttikiGreece Unit of Hepato-Pancreatic-Biliary Surgery “F.Miulli”Regional General HospitalAcquaviva delle Fonti 70021BariItaly Interventional Radiology Unit “F.Miulli”Regional General HospitalAcquaviva delle Fonti 70021Italy

Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.

关键词： Pancreatic cancer Interventional oncology Irreversible electroporation Ablation Loco-regional treatment Image-guided treatment

Awake robotic liver surgery:A case report

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2954-2961页

作者： antonella delvecchio Gaetano Pavone Maria Conticchio Claudia Piacente Miriam Varvara Valentina Ferraro Matteo Stasi Annachiara Casella Rosalinda Filippo Michele Tedeschi Carmine Pullano Riccardo Inchingolo Vito Delmonte Riccardo Memeo Unit of Hepato-Pancreatic-Biliary Surgery “F.Miulli”Regional General HospitalBari 70021Italy Unit of Anesthesia and Perioperative Medicine “F.Miulli”Regional General HospitalBari 70021Italy Villa Pia Hospital Rome 00151Italy Unit of Interventional Radiology “F.Miulli”Regional General HospitalBari 70021Italy

BACKGROUND In recent years,minimally invasive liver resection has become a standard of care for liver tumors.Considering the need to treat increasingly fragile patients,general anesthesia is sometimes avoided due to respiratory complications.Therefore,surgical treatment with curative intent is abandoned in favor of a less invasive and less radical approach.Epidural anesthesia has been shown to reduce respiratory complications,especially in elderly patients with pre-existing lung disease.CASE SUMMARY A 77-year-old man with hepatitis-C-virus-related chronic liver disease underwent robotic liver resection for hepatocellular carcinoma.The patient was suffering from hypertension,diabetes and chronic obstructive pulmonary disease.The National Surgical Quality Improvement Program score for developing pneumonia was 9.2%.We planned a combined spinal–epidural anesthesia with conscious sedation to avoid general anesthesia.No modification of the standard surgical technique was necessary.Hemodynamics were stable and bleeding was minimal.The postoperative course was uneventful.CONCLUSION Robotic surgery in locoregional anesthesia with conscious sedation could be considered a safe and suitable approach in specialized centers and in selected patients.

关键词： Robotic surgery Awake surgery Liver resection Frail patient Locoregional anesthesia Conscious sedation Case report

Impact of body mass index in elderly patients treated with laparoscopic liver resection for hepatocellular carcinoma

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World Journal of Gastrointestinal Surgery 2023年第1期15卷 72-81页

作者： Maria Conticchio Riccardo Inchingolo antonella delvecchio Francesca Ratti Maximiliano Gelli Massimiliano Ferdinando Anelli Alexis Laurent Giulio Cesare Vitali Paolo Magistri Giacomo Assirati Emanuele Felli Taiga Wakabayashi Patrick Pessaux Tullio Piardi Fabrizio di Benedetto Nicola de’Angelis Javier Briceño Antonio Rampoldi RenèAdam Daniel Cherqui Luca Antonio Aldrighetti Riccardo Memeo Unit of Hepato-Pancreatic-Biliary Surgery “F.Miulli”Regional General HospitalBari 70021Italy Interventional Radiology Unit “F.Miulli”Regional General HospitalBari 70021Italy Unit of Hepatobiliary Surgery San Raffaele HospitalMilano 20132Italy Departement de Chirurgie Viscérale Gustave Roussy Cancer Campus Grand ParisParis 94800France Unit of Oncologic and Pancreatic Surgery Hospital University Reina SofíaCordoba 14004Spain Assistance Publique-Hôpitaux de Paris Department of Digestive and Hepatobiliary SurgeryCentre Hospitalier Universitaire Henri MondorCréteilParis 94000France Service of Abdominal Surgery Poliambulanza FoundationBrescia 25124Italy Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41121Italy Institut de Recherche Contre les Cancers de l’Appareil Digestif(IRCAD) Strasbourg 67000France Service de Chirurgie Viscérale et Digestive Nouvel Hôpital CivilStrasbourg 67000France Department of Surgery Hôpital Robert DebréReims 51092France Interventional Radiology Unit Niguarda HospitalMilan 20162Italy Department of Surgery Centre HepatobiliaireHopital Paul BrousseParis 94000France

BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.

关键词： Hepatocellular carcinoma Body mass index Laparoscopy Surgical resection Elderly patients Propensity score matching

Peri-operative score for elderly patients with resectable hepatocellular carcinoma

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World Journal of Hepatology 2023年第12期15卷 1307-1314页

作者： Maria Conticchio Riccardo Inchingolo antonella delvecchio Francesca Ratti Maximiliano Gelli Massimiliano Ferdinando Anelli Alexis Laurent Giulio Cesare Vitali Paolo Magistri Giacomo Assirati Emanuele Felli Taiga Wakabayashi Patrick Pessaux Tullio Piardi Fabrizio di Benedetto Nicola de'Angelis Javier Briceño Antonio Rampoldi RenèAdam Daniel Cherqui Luca Antonio Aldrighetti Riccardo Memeo Unit of Hepato-Pancreatic-Biliary Surgery “F.Miulli”Regional General HospitalAcquaviva Delle Fonti 70021Italy Interventional Radiology Unit Department of Radiology“F.Miulli”Regional General HospitalAcquaviva Delle Fonti 75100Italy Hepatobiliary Surgery Division IRCSS San Raffaele Scientific InstituteMilan 20132Italy Hepatobiliary Surgery Division Vita-Salute San Raffaele UniversityMilan 20132Italy Département de Chirurgie Viscérale Gustave Roussy Cancer Campus Grand ParisParis 94800France Unit of Oncologic and Pancreatic Surgery Hospital University Reina SofíaCordoba 14004Spain Department of Digestive and Hepatobiliary Surgery Assistance Publique-Hôpitaux de ParisCréteil 94000France Service of Abdominal Surgery Poliambulanza FoundationBrescia 25124Italy Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41121Italy Department of Surgery Institut de Recherche Contre les Cancers de l'Appareil Digestif(IRCAD)Strasbourg 67000France Service de Chirurgie Viscérale et Digestive Nouvel Hôpital CivilUnitéINSERM U1110Strasbourg 67000France Department of Surgery Hôpital Robert DebréReims 51092France Assistance Publique-Hôpitaux de Paris Centre Hospitalier Universitaire Henri MondorParis 94000France Unit of Hepatobiliary Surgery and Liver Transplantation Hospital University Reina SofíaCordoba 14004Spain Interventional Radiology Unit Niguarda HospitalMilan 20162Italy Department of Surgery Centre HepatobiliaireHopital Paul BrousseParis 94000France

BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.

关键词： Hepatocellular carcinoma Score Laparoscopy Surgical resection Elderly patients Multivariate analysis

Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria

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World Journal of Gastroenterology 2021年第18期27卷 2205-2218页

作者： Maria Conticchio Riccardo Inchingolo antonella delvecchio Letizia Laera Francesca Ratti Maximiliano Gelli Ferdinando Anelli Alexis Laurent Giulio Vitali Paolo Magistri Giacomo Assirati Emanuele Felli Taiga Wakabayashi Patrick Pessaux Tullio Piardi Fabrizio di Benedetto Nicola de'Angelis Javier Briceño AntonioRampoldi RenèAdam Daniel Cherqui Luca Antonio Aldrighetti Riccardo Memeo Departement of Emergency and Trasplantation of Organs General Surgery Unit“M.Rubino”Policlinico di BariBari 70124Italy Interventional Radiology Unit "F.Miulli"General Regional HospitalAcquaviva delle Fonti 70021Italy Department of Emergency and Organ Transplantation General Surgery Unit“M.Rubino”University of BariCeglie Messapica 70124Italy Department of Oncology "F.Miulli"General Regional HospitalAcquaviva delle Fonti 70021Italy Department of Surgery Univ Vita Salute San RaffaeleMilan 20132Italy Department of Visceral and Oncological Surgery Gustave Roussy Cancer Campus Grand ParisVillejuif 94800France Unit of Oncologic and Pancreatic Surgery Hospital University Reina SofíaCordoba 14004Spain Department of Digestive and Hepatobiliary Surgery Henri Mondor University HospitalCreteil 94000France Department of Surgery University of Geneva HospitalsGeneva 44041Switzerland Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41124Italy Institut de Recherche Contre les Cancers de l'Appareil Digestif Strasbourg 67000France Department of Surgery Keio University School of MedicineShinjuku-ku 160-8582Japan Hepato-Biliary and Pancreatic Surgical Unit Nouvel Hôpital CivilStrasbourg cedex 67091France Department of Hepatobiliary Pancreatic and Digestive SurgeryUniversity Hospital Robert Debréof ReimsReims 51100France Hepatobiliary and Pancreatic Surgery Unit General Surgery DepartementTroyes HospitalTroyes Zip or Postal CodeFrance University of Champagne-Ardenne Reims 51100France Unit of Minimally Invasive and Robotic Digestive Surgery "F.Miulli"General Regional HospitalAcquaviva delle Fonti 70021Italy Department of General and Digestive Surgery Reina Sofia University HospitalCordoba 14004Spain Interventional Radiology Unit Niguarda HospitalMilan 20132Italy 20132 Italy RenèAdam Hepatobiliary Center Hopital Paul BrousseVillejuif 94800France Unit of Hepato-Pancreatic-Biliary Surgery Univ Vita Salute San RaffaeleMilan 20132Italy Uni

BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.

关键词： Hepatocellular carcinoma Milan criteria Radiofrequency ablation Surgical resection Elderly patients Propensity score matching

Liver resection vs radiofrequency ablation in single hepatocellular carcinoma of posterosuperior segments in elderly patients

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World Journal of Gastrointestinal Surgery 2021年第12期13卷 1696-1707页

作者： antonella delvecchio Riccardo Inchingolo Rita Laforgia Francesca Ratti Maximiliano Gelli Massimiliano Ferdinando Anelli Alexis Laurent Giulio Vitali Paolo Magistri Giacomo Assirati Emanuele Felli Taiga Wakabayashi Patrick Pessaux Tullio Piardi Fabrizio di Benedetto Nicola de'Angelis Javier Briceño Antonio Rampoldi RenèAdam Daniel Cherqui Luca Antonio Aldrighetti Riccardo Memeo Unit of General Surgery "A.Perrino"HospitalCeglie Messapica 70124BariItaly Interventional Radiology Unit "F.Miulli"General Regional HospitalAcquaviva delle Fonti 75100Italy Unit of Laparoscopic Surgery University of BariBary 70124Italy Unit of Hepato-Pancreatic-Biliary Surgery University Vita Salute San RaffaeleMilan 20132Italy Department of Surgical Oncology Gustave Roussy Cancer Campus Grand ParisVillejuif 94800France of General Surgery Reina Sofia University HospitalCordoba 14004Spain Department of Digestive and Hepatobiliary Surgery Henry Mondor University HospitalCreteil 94000France Division of Transplantation Geneva University HospitalGeneva 44041Switzerland Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 42121Italy Department of Digestive Surgery Strasbourg University HospitalStrasbourg 67000France Department of Digestive and Hepatobiliary Surgery Robert DebrèUniversity HospitalReims 51100France Unit of Minimally Invasive and Robotic Digestive Surgery "F.Miulli"General Regional HospitalAcquaviva delle Fonti 70124Italy Interventional Radiology Unit Niguarda HospitalMilan 20162Italy Department of Hepatobiliary Surgery Paul Brousse University HospitalVillejuif 94800France Department of Hepatobiliary Surgery University Vita Salute San RaffaeleMilan 20132Italy Unit of Hepato-Pancreatic-Biliary Surgery "F.Miulli"General Regional HospitalAcquaviva delle Fonti 70124Italy

BACKGROUND Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma.The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients.AIM To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments.METHODS A retrospective multicentric study was performed enrolling 77 patients age≥70-years-old with single hepatocellular carcinoma(≤30 mm),located in posterosuperior segments(4a,7,8).Patients were divided into liver resection and radiofrequency ablation groups and preoperative,peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching.RESULTS After propensity score matching,twenty-six patients were included in each group.Operative time and overall postoperative complications were higher in the resection group compared to the ablation group(165 min vs 20 min,P<0.01;54%vs 19%P=0.02 respectively).A median hospital stay was significantly longer in the resection group than in the ablation group(7.5 d vs 3 d,P<0.01).Ninety-day mortality was comparable between the two groups.There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1,3,and 5 years.CONCLUSION Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay,better quality of life and does not modify the overall and disease-free survival.

关键词： Elderly Hepatocellular carcinoma Posterosuperior segments Liver resection Radiofrequency ablation Multicentric study

B cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2022年第11期28卷 1088-1101页

作者： Francesca Romana delvecchio Michelle R Goulart Rachel Elizabeth Ann Fincham Michele Bombadieri Hemant M Kocher William Harvey Research Institute Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts Cancer Institute Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre Barts Health NHS TrustLondon E11BBUnited Kingdom

Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression.In human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient survival.Hence,B cells have received recent interest in pancreatic cancer as potential therapeutic targets.However,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study.Nevertheless,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma cells.In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.

关键词： B cells Pancreatic cancer Cancer immunology Tertiary lymphoid structures Anti-tumour immunoglobulins Plasma cells

Surgical resection of rare internal jugular vein aneurysm in neurofibromatosis type 1

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World Journal of Clinical Cases 2017年第12期5卷 419-422页

作者： Khortnal delvecchio Fazaldin Moghul Bipinchandra Patel Susan Seman Department of Surgery Detroit Medical Center Huron Valley-Sinai Hospital Department of Surgery Detroit Medical Center Sinai Grace Hospital

Neurofibromatosis type 1 is a congenital condition affecting neurons and connective tissue integrity including vasculature.On extremely rare occasions these patients present with venous aneurysms affecting the internal jugular vein.If they become large enough there presents a risk of rupture,thrombosis,embolization or compression of adjacent structures.In these circumstances,or when the patient becomes symptomatic,surgical exploration is warranted.We present a case of one of the largest aneurysms in the literature and one of only five associated with Neurofibromatosis type 1.A 63-year-old female who initially presented for a Hinchey Ⅲ diverticulitis requiring laparotomy developed an incidentally discovered left neck swelling prior to discharge.After nonspecific clinical exam findings,imaging identified a thrombosed internal jugular vein aneurysm.Due to the risks associated with the particularly large size of our patient's aneurysm,our patient underwent surgical exploration with ligation and excision.Although several techniques have been reported,for similar presentations,we recommend this technique.

关键词： Internal jugular Venous aneurysm Ligation Neurofibromatosis 1 Excision Resection

T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： Michelle R Goulart Konstantinos Stasinos Rachel Elizabeth Ann Fincham Francesca R delvecchio Hemant M Kocher Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival rate.PDAC has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T cells.The cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant organs.PDAC tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted phenotype.Here,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion Tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma