48 results on '"Michele Carvello"'
Search Results
2. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.
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Giuseppe Di Caro, Michele Carvello, Samantha Pesce, Marco Erreni, Federica Marchesi, Jelena Todoric, Matteo Sacchi, Marco Montorsi, Paola Allavena, and Antonino Spinelli
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Medicine ,Science - Abstract
Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients.Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0-IV CRC and associated with post-operative disease recurrence.Cox multivariate analysis showed that combined high levels (≥ROC cut off-value) of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13-65.1)] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P
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- 2016
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3. Transanal Transection and Single-Stapled Anastomosis (TTSS): A comparison of anastomotic leak rates with the double-stapled technique and with transanal total mesorectal excision (TaTME) for rectal cancer
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G. Clerico, Caterina Foppa, Richard J. Heald, Matteo Sacchi, Antonino Spinelli, Annalisa Maroli, Francesco Maria Carrano, Francesca De Lucia, Michele Carvello, and Marco Montorsi
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Male ,medicine.medical_specialty ,Leak ,Colorectal cancer ,medicine.medical_treatment ,Anastomotic Leak ,Anastomosis ,Postoperative Complications ,Surgical Stapling ,medicine ,Humans ,Prospective Studies ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Stapled anastomosis ,Rectal Neoplasms ,business.industry ,Anastomosis, Surgical ,General Medicine ,Middle Aged ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Total mesorectal excision ,Surgery ,Dissection ,Oncology ,Anal verge ,Female ,Laparoscopy ,business - Abstract
in the literature on rectal cancer (RC) surgery many studies have focused on the quality of total mesorectal excision (TME) dissection, while there is a scarcity of comparative data on transection and anastomosis. No anastomosis has so far proved to be superior to any other. The aim of this study was to compare anastomotic leak (AL) rates between conventional laparoscopic double-stapled (DS), transanal total mesorectal excision (TaTME) and Transanal Transection and Single-Stapled anastomosis (TTSS) techniques.consecutive mid-low RC patients undergoing elective laparoscopic TME with stapled anastomosis and protective stoma, by either DS, TaTME or TTSS techniques were retrieved from a prospectively collected database.127 DS; 100 TaTME and 50 TTSS were included. Demographics, distance of the tumor from anal verge and neoadjuvant therapy were comparable. Operative time was longer in TaTME over DS and TTSS (p 0.0001). More 90-days complications occurred in DS group vs TTSS (p = 0.029). The AL rate was 17.5% in DS, 6% in TaTME and 2% in TTSS group (p = 0.005). AL grade was: one B (2%) in TTSS; 2 grade B (2%) and 4 grade C (4%) in TaTME; 6 grade A (4.7%), 7 grade B (5.5%) and 9 grade C (7.1%) in DS group. Reintervention rate after AL was higher in DS group over TTSS (12.6% vs 2%; p = 0.003). The rate of stoma closure, pathology data and margin positivity did not differ.TTSS strategy is feasible, safe and leads to very low AL rates after TME for RC.
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- 2021
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4. Rectal Cancer in Adolescent and Young Adult Patients: Pattern of Clinical Presentation and Case-Matched Comparison of Outcomes
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André D'Hoore, Caterina Foppa, Michele Carvello, Annalisa Maroli, Marco Montorsi, Albert Wolthuis, Luigi Laghi, Alexia Bertuzzi, Fabio Cianchi, Lorenza Rimassa, and Antonino Spinelli
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Adult ,Male ,medicine.medical_specialty ,Delayed Diagnosis ,Adolescent ,Colorectal cancer ,Stage iv disease ,Locally advanced ,Delayed diagnosis ,Disease-Free Survival ,Young Adult ,Older patients ,medicine ,Advanced disease ,Humans ,Young adult ,Clinical presentation ,Outcomes ,Rectal cancer ,Young ,Medical History Taking ,Neoplasm Staging ,Retrospective Studies ,Gynecology ,Rectal Neoplasms ,business.industry ,Carcinoma ,Age Factors ,Gastroenterology ,General Medicine ,medicine.disease ,Neoadjuvant Therapy ,Survival Rate ,Microsatellite Stable ,Female ,Microsatellite Instability ,Gastrointestinal Hemorrhage ,business - Abstract
BACKGROUND Rectal cancer in adolescents and young adults (age ≤39) is increasing. Early diagnosis is a challenge in this subset of patients. OBJECTIVE This study aims to analyze the presentation pattern and outcomes of sporadic rectal cancer in adolescents and young adults. DESIGN This is a retrospective study. SETTING This study was conducted at 3 European tertiary centers. PATIENTS Data on adolescents and young adults operated on for sporadic rectal cancer (January 2008 through October 2019) were analyzed. To compare outcomes, adolescents and young adults were matched to a group of patients aged ≥40 operated on during the same period. MAIN OUTCOME MEASURES The primary outcomes measured were clinical presentation and long-term outcomes. RESULTS Sporadic rectal cancers occurred in 101 adolescents and young adults (2.4%; mean age, 33.5; range, 18-39); 51.5% were male, and a smoking habit was reported by 17.8% of patients. The rate of a family history for colorectal cancer was 25.7%, and of these patients, 24.7% were obese. Diagnosis based on symptoms was reported in 92.1% patients, and the mean time from first symptoms to diagnosis was 13.7 months. The most common symptom at diagnosis was rectal bleeding (68.8%), and 12% and 34% of the adolescents and young adults presented with locally advanced or metastatic disease at diagnosis. Consequently, 68.3% and 62.4% adolescents and young adults received neoadjuvant and adjuvant treatments. The rate of complete pathological response was 24.1%; whereas 38.6% patients had stage IV disease, and 93.1% were microsatellite stable. At a mean follow-up of 5 years, no difference in cancer-specific survival, but a lower disease-free survival was reported in adolescents and young adults (p < 0.0001) vs the matched group. Adolescents and young adults with stages I to II disease had shorter cancer-specific survival and disease-free survival (p = 0.006; p < 0.0001); with stage III disease, they had a shorter disease-free survival (p = 0.01). LIMITATIONS This study was limited by its observational, retrospective design. CONCLUSIONS The significantly delayed diagnosis in adolescents and young adults may have contributed to the advanced disease at presentation and lower disease-free survival, even at earlier stages, suggesting a higher metastatic potential than in older patients. See Video Abstract at http://links.lww.com/DCR/B537. CNCER DE RECTO EN PACIENTES ADOLESCENTES Y ADULTOS JVENES CUADRO DE PRESENTACIN CLNICA Y COMPARACIN DE DESENLACES POR CASOS EMPAREJADOS ANTECEDENTES:El cancer de recto en adolescentes y adultos jovenes (edad ≤ 39) esta aumentando. El diagnostico temprano es un desafio en este subgrupo de pacientes.OBJETIVO:Analizar el cuadro de presentacion y los desenlaces en adolescentes y adultos jovenes con cancer de recto esporadico.DISENO:Estudio retrospectivo.AMBITO:Tres centros europeos de tercer nivel.PACIENTES:Se analizaron los datos de adolescentes y adultos jovenes operados de cancer de recto esporadico (enero de 2008 - octubre de 2019). Para comparar los desenlaces se emparejo a adolescentes y adultos jovenes con un grupo de pacientes mayores de 40 anos operados en el mismo periodo de tiempo.PRINCIPALES VARIABLES ANALIZADAS:Cuadro clinico, resultados a largo plazo.RESULTADOS:Los canceres de recto esporadicos en adolescentes y adultos jovenes fueron 101 (2,4%, edad media: 33,5, rango 18-39). El 51,5% eran hombres, el 17,8% de los pacientes fumaba. El 25,7% tentia antecedentes familiares de cancer colorrectal. El 24,7% eran obesos. El diagnostico con base en los sintomas se informo en el 92,1% de los pacientes, el tiempo promedio desde los primeros sintomas hasta el diagnostico fue de 13,7 meses. El sintoma mas comun en el momento del diagnostico fue el sangrado rectal (68,8%). 12% y 34% de adolescentes y adultos jovenes presentaron enfermedad localmente avanzada o metastasica en el momento del diagnostico. Por lo tanto, el 68,3% y el 62,4% de adolescentes y adultos jovenes recibieron neoadyuvancia y adyuvancia. La tasa de respuesta patologica completa fue del 24,1%; mientras que el 38,6% estaban en estadio IV. El 93,1% eran microsatelite estable. Con una media de seguimiento de 5 anos, no se observaron diferencias en la sobrevida especifica del cancer, pero se informo una menor sobrevida libre de enfermedad en adolescentes y adultos jovenes (p
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- 2021
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5. A scoring system to predict a prolonged length of stay after surgery for Crohn’s disease
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Antonino Spinelli, Kapil Sahnan, Dakshitha Wickramasinghe, Michele Carvello, Samuel O Adegbola, Pritesh Morar, Janindra Warusavitarne, Francesca Di Candido, and Annalisa Maroli
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medicine.medical_specialty ,Scoring system ,Multivariate analysis ,medicine.medical_treatment ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,medicine ,Strictureplasty ,Humans ,Postoperative Period ,Colectomy ,Retrospective Studies ,Crohn's disease ,Receiver operating characteristic ,business.industry ,Anastomosis, Surgical ,Gastroenterology ,Regression analysis ,Perioperative ,Length of Stay ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
AIM Many factors influence the postoperative length of stay (LOS) in Crohn's disease (CD). This study aims to identify the factors associated with a prolonged LOS after ileocolic resection (ICR) for CD and to develop a scoring system to predict the postoperative LOS in CD. METHOD Patient data were collected from St Marks Hospital, London, UK, and the Humanitas Clinical and Research Center Milan, Italy, for all patients who underwent an ICR for CD from 2005 to 2017. Logistic regression was used for multivariate analysis. The scoring system was developed from the logistic regression model. The performance of the scoring system was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS A total of 628 surgeries were included in the analysis. Eighty eight surgeries were excluded due to missing data. The remaining 543 were divided into two cohorts for the development (n = 418) and validation (n = 125) of the scoring system. The regression model was statistically significant (p
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- 2021
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6. Robotic Surgery in Inflammatory Bowel Disease
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Jacopo Crippa, Paulo Gustavo Kotze, Antonino Spinelli, and Michele Carvello
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Pharmacology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,General surgery ,Clinical Biochemistry ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Inflammatory bowel disease ,Colorectal surgery ,Conversion to open surgery ,Robotic Surgical Procedures ,Artificial Intelligence ,Drug Discovery ,medicine ,Humans ,Molecular Medicine ,Laparoscopy ,Robotic surgery ,Technical skills ,business ,Retrospective Studies - Abstract
Background: Surgery is considered a cornerstone of inflammatory bowel disease (IBD) treatment. In the last years, robotic surgery has seen an increase in adoption rates for both benign and malignant diseases. Objective: This work aims to review the current applications of robotic surgery in IBD. Discussion and Conclusion: Minimally-invasive techniques have been applied to the treatment of IBD for more than 20 years. Investments in surgical digital and robotic platforms are increasingly arising, with an estimate of getting doubled within the next 5 years. Robotic surgery represents the newest technology available to reduce the impact of surgery on patients affected by IBD, and may theoretically be even more effective than other minimally-invasive techniques given the lower rate of conversion to open surgery as compared to laparoscopy according to many large retrospective series. Data on robotic surgery applied to IBD are still scarce and initial experiences in high-volume centers from retrospective series suggested that robotic surgery may achieve similar results when compared to laparoscopy. A new wave of robotics incorporating artificial intelligence is awaited to empower the capability of IBD surgeon in terms of intraoperative decision-making beyond technical skill enhancement.
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- 2020
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7. The trend of C-Reactive protein allows a safe early discharge after surgery for Crohn’s disease
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Francesca Di Candido, Annalisa Maroli, Caterina Foppa, Gionata Fiorino, Silvio Danese, Maurizio Cecconi, Michele Carvello, Massimiliano Greco, Antonino Spinelli, Carvello, Michele, Di Candido, Francesca, Greco, Massimiliano, Foppa, Caterina, Maroli, Annalisa, Fiorino, Gionata, Cecconi, Maurizio, Danese, Silvio, and Spinelli, Antonino
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Crohn's disease ,medicine.medical_specialty ,education.field_of_study ,biology ,business.industry ,C-reactive protein ,Population ,Area under the curve ,Anastomosis ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,biology.protein ,030211 gastroenterology & hepatology ,Clinical significance ,Elective surgery ,education ,business ,Early discharge - Abstract
Postoperative C-reactive protein (CRP) level allows to rule out infectious complications ensuring safe hospital discharge in colorectal cancer surgery. Since its clinical significance in Crohn’s disease (CD) has not been studied yet, we investigated whether CRP can guide decision-making on hospital discharge in this population. Only consecutive CD patients undergoing resections with primary anastomosis and without covering stoma (2013–2017) were analysed. Pre- and post-operative CRP values, measured daily until discharge, were correlated with postoperative complications including anastomotic leakage (AL), infectious and non-infectious complications. The diagnostic accuracy of CRP in predicting AL was evaluated according to the area under the curve (AUC), using the receiver-operating characteristic (ROC) methodology. Two-hundred and fifty-one consecutive patients undergoing elective surgery for CD were selected. AL was diagnosed in 10 patients (4%). High CRP level was associated with AL on postoperative day (POD) 3–5 (p = 0.002, AUC 0.825) with a positive predictive value of 60%. CRP linear difference of 140 between POD 1 and 3 (AUC 0.800) maximizes sensitivity and specificity with a NPV of 98.6%. CRP trend, measured with the linear difference between POD 1 and 3, is able to rule out anastomotic complications with a high NPV and may allow a safe early hospital discharge after surgery for CD.
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- 2020
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8. Up-to-date surgery for ulcerative colitis in the era of biologics
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Amy L. Lightner, Antonino Spinelli, Michele Carvello, Takayuki Yamamoto, and Paulo Gustavo Kotze
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0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Clinical Biochemistry ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Humans ,Colitis ,Pharmacology ,Biological Products ,Management of ulcerative colitis ,business.industry ,Adalimumab ,medicine.disease ,Ulcerative colitis ,Surgery ,030104 developmental biology ,030220 oncology & carcinogenesis ,Acute Disease ,Colitis, Ulcerative ,Ustekinumab ,business ,Algorithms - Abstract
Introduction: In recent decades, biologics have resulted in significantly improved medical management of ulcerative colitis (UC). Rates of surgery for UC are declining. However, there is still a co...
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- 2020
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9. Assessing the development status of intraoperative fluorescence imaging for perfusion assessments, using the IDEAL framework
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Yasuo Murai, Giovanni Dapri, Eric Vibert, Ronan A. Cahill, Charles Sabbagh, Ory Wiesel, Antonino Spinelli, Luigi Boni, Michele Diana, Elisa Cassinotti, Mahmoud Abu-Gazala, Michael Bouvet, Kiyoshi Hasegawa, Raul J. Rosenthal, Derek D. Muehrcke, Frédéric Ris, Michele Carvello, Thomas Carus, Muga Terasawa, Norihiro Kokudo, Sylke Schneider-Koriath, Peter McCulloch, Mikiya Takao, Kevin P. White, Rutger M. Schols, Steven D. Wexner, Fumihiro Matano, Fernando Dip, Takeaki Ishizawa, Tim Pruimboom, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA AIOS Plastische Chirurgie (9), Plastische Chirurgie (PLC), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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medicine.medical_specialty ,Reconstructive surgery ,RD1-811 ,Biomedical Engineering ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Medical technology ,Medicine ,R855-855.5 ,Stage (cooking) ,Adverse effect ,health technology ,Original Research ,Ideal (set theory) ,business.industry ,device evaluation ,Colorectal surgery ,development study ,chemistry ,Surgery ,Radiology ,business ,Perfusion ,Indocyanine green - Abstract
ObjectivesIntraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: assessing tissue perfusion; identifying/localizing cancer; mapping lymphatic systems; and visualizing anatomy. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging for perfusion assessments using the Idea, Development,Exploration, Assessment, Long Term Study (IDEAL) framework, which was designed for describing the stages of innovation in surgery and other interventional procedures.DesignNarrative literature review with analysis of IDEAL stage of each field of study.SettingAll publications on intraoperative fluorescence imaging for perfusion assessments reported in PubMed through 2019 were identified for six surgical procedures: coronary artery bypass grafting (CABG), upper gastrointestinal (GI) surgery, colorectal surgery, solid organ transplantation, reconstructive surgery, and cerebral aneurysm surgery.Main outcome measuresThe IDEAL stage of research evidence was determined for each specialty field using a previously described approach.Results196 articles (15 003 cases) were selected for analysis. Current status of research evidence was determined to be IDEAL Stage 2a for upper GI and transplantation surgery, IDEAL 2b for CABG, colorectal and cerebral aneurysm surgery, and IDEAL Stage 3 for reconstructive surgery. Using the technique resulted in a high (up to 50%) rate of revisions among surgical procedures, but its efficacy improving postoperative outcomes has not yet been demonstrated by randomized controlled trials in any discipline. Only one possible adverse reaction to intravenous indocyanine green was reported.ConclusionsUsing fluorescence imaging intraoperatively to assess perfusion is feasible and appears useful for surgical decision making across a range of disciplines. Identifying the IDEAL stage of current research knowledge aids in planning further studies to establish the potential for patient benefit.
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- 2021
10. A Multidisciplinary Approach to Rectal Cancer Treatment in Ulcerative Colitis Results in High Rate of Restorative Minimally Invasive Surgery
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Silvio Danese, Vittoria Bellato, Ailsa Hart, Michele Carvello, Annalisa Maroli, Janindra Warusavitarne, and Antonino Spinelli
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High rate ,medicine.medical_specialty ,Referral ,business.industry ,Colorectal cancer ,Rectal Neoplasms ,Proctocolectomy, Restorative ,Gastroenterology ,Multimodal therapy ,General Medicine ,medicine.disease ,Ulcerative colitis ,Surgery ,Treatment Outcome ,Concomitant ,Medicine ,Adenocarcinoma ,Humans ,Minimally Invasive Surgical Procedures ,Colitis, Ulcerative ,business ,Survival rate ,Retrospective Studies - Abstract
Background and Aims Few recent studies focus on the treatment of rectal cancer in patients with ulcerative colitis. We report treatment options and results for this subset of patients with a multimodal approach at two European referral centres. Methods Ulcerative colitis patients diagnosed with rectal cancer arising at less than 15 cm from the anal verge between January 2010 and December 2020 were analysed. Demographics, clinical data, and details of medical and surgical treatment were retrieved from prospectively collected institutional databases. Results Of 132 patients with ulcerative colitis and concomitant colorectal cancer, rectal cancer was diagnosed in 46. The median time between disease onset and rectal cancer diagnosis was 17.5 years; 21/46 were preoperatively staged as early tumours [cT1-T2/N0]. Eleven patients received neoadjuvant chemoradiotherapy for locally advanced extraperitoneal adenocarcinoma, and the rest underwent surgery first. Over two-thirds of the procedures were restorative [68%]; a minimally invasive approach was used in 96% of patients, with no conversion to open. The median follow-up was 44 months. Local recurrence occurred in three patients [6%]. The cumulative 3-year cancer-specific survival rate was 94% [and the 3-year disease-free rate was 86%]. Conclusions Rectal cancer in ulcerative colitis is a very complex condition. Our results show that surgery for rectal cancer can be delivered with excellent oncological and functional outcomes in patients with ulcerative colitis. A multidisciplinary discussion among surgeons, gastroenterologists, and medical oncologists is key to ensure the appropriate treatment pathway for individual patients.
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- 2021
11. Early age of onset is an independent predictor for worse disease-free survival in sporadic rectal cancer patients. A comparative analysis of 980 consecutive patients
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José Perea, L. Poliani, Annalisa Maroli, Caterina Foppa, A. Malesci, Marco Montorsi, Antonino Spinelli, Sara Tamburello, Luigi Laghi, and Michele Carvello
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medicine.medical_specialty ,Colorectal cancer ,Gene mutation ,medicine.disease_cause ,Gastroenterology ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Stage (cooking) ,Family history ,Age of Onset ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Rectal Neoplasms ,Microsatellite instability ,General Medicine ,medicine.disease ,Prognosis ,Progression-Free Survival ,Oncology ,Surgery ,KRAS ,Age of onset ,Neoplasm Recurrence, Local ,business - Abstract
BACKGROUND while interest on early-onset colorectal cancer (age ≤49) is on the rise, studies on early-onset rectal cancer (EORC) are limited. The aim of this study was to compare predictors for disease progression/recurrence between sporadic EORC and late-onset RC patients (LORC). METHODS 163 EORC and 830 LORC operated between January 1st, 2010 and April 30th, 2021 at a tertiary center were included. Demographics, tumor characteristics, microsatellite status, gene mutations (KRAS, BRAF, NRAS, PI3Kca) and oncologic outcomes were compared. A Cox proportional hazards regression analysis was performed to ascertain the effect of variables on recurrence/progression and death. Recurrence/Progression free survival (R/PFS) and cancer specific survival (CSS) were analyzed by the Kaplan-Meier estimator. RESULTS Mean age of EORC was 42.16, (46% aged 45-49). A majority of EORC patients had a family history for CRC (p = 0.01) and underwent total neoadjuvant treatment (p = 0.01). EORC patients showed a higher rate of low-grade tumor differentiation (p
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- 2021
12. Transanal Ileal Pouch-Anal Anastomosis for Ulcerative Colitis has Comparable Long-Term Functional Outcomes to Transabdominal Approach: A Multicentre Comparative Study
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Pramodh Chandrasinghe, Zarah L Perry‐Woodford, Caterina Foppa, Willem A. Bemelman, Karin A. T. G. M. Wasmann, Antonino Spinelli, Pieter J. Tanis, Michele Carvello, Janindra Warusavitarne, Graduate School, Surgery, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Adult ,Male ,Reoperation ,Comparative Effectiveness Research ,medicine.medical_specialty ,Urology ,Anal Canal ,Colonic Pouches ,Long Term Adverse Effects ,Anastomotic Leak ,Urinary incontinence ,Anastomosis ,Postoperative Complications ,Quality of life ,medicine ,Clinical endpoint ,Humans ,Pouch anal anastomosis ,Lesser Pelvis ,business.industry ,Abdominal Wall ,Proctocolectomy, Restorative ,Gastroenterology ,Recovery of Function ,General Medicine ,medicine.disease ,Ulcerative colitis ,Transanal surgery ,Ileal Pouch Anal Anastomosis ,Europe ,Quality of Life ,Colitis, Ulcerative ,Female ,medicine.symptom ,Pouch ,business ,Cohort study - Abstract
Background The transanal approach to ileal pouch-anal anastomosis [Ta-IPAA] provides better access to the lower pelvis with lower short-term morbidity in ulcerative colitis [UC]. The aim of this study was to assess the long-term functional outcomes after Ta-IPAA vs transabdominal IPAA [Abd-IPAA] in UC. Methods A multicentre cohort analysis was performed between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. CGQL [Cleveland global quality of life] score at 12 months with a functioning pouch was considered the primary end point. Results A total of 374 patients [100 Ta-IPAA vs 274 Abd-IPAA] were included. Ta-IPAA demonstrated a comparable overall quality of life [CGQL score] to Abd-IPAA [0.75 ± 0.11 vs 0.71 ± 0.14; respectively, p = 0.1]. Quality of life [7.71 ± 1.17 vs 7.30 ± 1.46; p = 0.04] and energy-level items [7.16 ± 1.52 vs 6.66 ± 1.68; p = 0.03] were significantly better after Ta-IPAA, while the quality of health item was comparable [7.68 ± 1.26 vs 7.64 ± 1.44; p = 0.96]. Analysis excluding anastomotic leaks did not change the overall CGQL scores. Stool frequencies [>10/24 h: 22% vs 21%; p = 1.0] and the rate of a single episode of major incontinence during the following 12-month period [27% vs 26%; p = 0.89] were similar. The differences in 30-day morbidity rates [33% vs 41%; p = 0.2] and anastomotic leak rates were not significant [6% vs 13%; p = 0.09]. Conclusions This study provides evidence of comparable long-term functional outcome and quality of life after Ta-IPAA and Abd-IPAA for UC.
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- 2019
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13. Laparoscopic Intracorporeal Double Purse-String Ileorectal Anastomosis With Transanal Natural Orifice Specimen Extraction
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Antonino Spinelli, Francesco Maria Carrano, Caterina Foppa, G. Clerico, and Michele Carvello
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Male ,Natural Orifice Endoscopic Surgery ,medicine.medical_specialty ,business.industry ,Anastomosis, Surgical ,String (computer science) ,Rectum ,Gastroenterology ,General Medicine ,Middle Aged ,Natural orifice ,Specimen Handling ,Surgery ,Surgical Staplers ,Treatment Outcome ,Ileorectal anastomosis ,Ileum ,Colonic Neoplasms ,medicine ,Humans ,Laparoscopy ,business ,Colectomy - Published
- 2021
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14. Patients’ perceptions of surgery for inflammatory bowel disease
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Antonino Spinelli, André D'Hoore, Silvio Danese, Francesco Pagnini, Yves Panis, Lucie Lastikova, Janindra Warusavitarne, Paulo Gustavo Kotze, Laurent Peyrin-Biroulet, Michel Adamina, Willem A. Bemelman, Luisa Avedano, Hagit Tulchinsky, Michele Carvello, Surgery, and Amsterdam Gastroenterology Endocrinology Metabolism
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medicine.medical_specialty ,media_common.quotation_subject ,Ulcerative ,Disease ,Settore M-PSI/08 - PSICOLOGIA CLINICA ,Inflammatory bowel disease ,patients ,Stoma ,Quality of life ,Crohn Disease ,medicine ,Humans ,Risks and benefits ,media_common ,business.industry ,Gastroenterology ,perception of surgery ,medicine.disease ,Inflammatory Bowel Diseases ,Colitis ,Ulcerative colitis ,patients reported outcomes ,Surgery ,Patient perceptions ,Feeling ,quality of life ,stoma acceptance ,Perception ,Colitis, Ulcerative ,feelings ,business - Abstract
Aim: Surgery is indicated in selected patients with inflammatory bowel disease (IBD). However, due to a negative perception, surgery may be delayed, leading to possible unfavourable outcomes. The aim of this work was to investigate patients’ perceptions of surgery and the impact on reported outcomes. Method: An international multilingual online survey was used to query IBD patients’ experiences of surgery, information sources, expectations and concerns, quality of life (QoL) and feelings. Results: The survey was completed by 425 of 510 participants. Crohn's disease was more frequent (61%) than ulcerative colitis (36%). Most patients primarily learned about surgery from their gastroenterologist and were informed of the risks and benefits by the surgeon. In almost one-third of patients indication for surgery was not a shared decision between gastroenterologist and surgeon. Seventy per cent of patients naïve to surgery were not aware of any surgical options. The majority of patients (80%) perceived surgery as the last option after many medical treatments rather than an alternative therapeutic option (20%). Sixteen per cent of patients obtained their primary information from the Internet, while 82.4% used the Internet to obtain additional information. Fear of surgical complications was cited by 73% of patients, while relief from symptoms was indicated by 31%. Most patients coped with their stoma better than expected or as they expected. Negative feelings decreased after surgery, while a lasting improvement in positive feelings and QoL was reported. Conclusion: Despite the negative perception of surgery and the delayed involvement of surgeons as a source of information and in the decision-making process, the majority of respondents experienced positive outcomes from surgery, including improvement QoL and acceptance of the stoma.
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- 2021
15. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review
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Nancy You, Monica Millan, Sergio Nahas, Barisic Goran, Tim Forgan, Daniela Rega, Frederic Ris, Tongplaew Singnomklao, Maylis Capdepont, Cameron Wells, Aleksei Karachun, Alaa El-Hussuna, Martin Schneider, Jaime Otero, M. Evans, Neils Kok, Guillaume Meurette, Luis Oñate-Ocaña, Tomas Contreras, Augustinas Bausys, Alexandra M Zaborowski, Aleksandra Edmundson, Miklosh Bala, David Proud, Petr Tsarkov, Satish K Warrier, Ivana Raguz, Gleb Khrykov, Cherry Koh, F. McDermott, Aleksandar Sekulic, Rebecca Shine, Daniel D. Buchanan, Scott R. Steele, Kai-Yin Lee, Ugo Pace, Sean T. Martin, Nelleke P.M. Brouwer, Cihan Ozen, Nuno Rama, Lene Hjerrild Iversen, Ann Hanly, Sabrina Tengku, Heather Hampel, Dieter Hahnloser, G Bislenghi, Seraina Faes, Meike Van Harten, Ahmed Abdile, Shamil Gadaev, Said Kural, Neil J. Smart, Ionut Negoi, Rory Kennelly, Alexandra Olkina, Albert Wolthuis, Ian R. Daniels, Benjamin A. Weinberg, Jason Park, Dave Larson, Roland Croner, Ryo Seishima, Michel Adamina, P Terry Phang, Felix Aigner, Fergal J. Fleming, Christopher H. Lieu, Craig Lynch, Ugne Imbrasaite, Mihailo Andric, Marc Bludau, Omar Faiz, Manoj J. Raval, Deborah Saraste, Michela Campanelli, Sebastiano Biondo, Sam Atallah, Zoran Krivokapic, Evgeniy Drozdov, Michele Carvello, Pamela Buchwald, Alexander Zakharenko, Vicki Bevan, Giovanni Dapri, Ker-Kan Tan, James Hill, Lynette Loi, Melissa-Rose Bennett, Justin Kelly, Jérémie H. Lefevre, Pieter J. Tanis, Avanish Saklani, Juan Carlos Patrón Uriburu, Shahnawaz Rasheed, John R. T. Monson, Alexandra Shlomina, Roxane D Staiger, Timur Lankov, Caio Nahas, Nikita Burlov, Marianne Grønlie Guren, Swati G. Patel, Evangelos Xynos, Andrew D Beggs, Christos Kontovounisios, Annalisa Maroli, Yves Panis, Simon P. Bach, Campbell S.D. Roxburgh, Peter Kocian, Rodrigo O Perez, Michael Sunderland, Fabiano Iaquinandi, Justin Davies, György Lázár, Carl J. Brown, Andrea Jiménez Salido, Jiri Hoch, Malcolm G. Dunlop, Anna Lepistö, Tamara Glyn, Deborah S. Keller, Felipe Bellolio, Juan Carlos Reyes Meneses, Hirotoshi Hasegawa, Andre Dias, Hans de Wilt, Rocio Anula, Christoph Reissfelder, George E Fowler, Marie Barussaud, Demetris Papamichael, Martino Munini, Andrew G. Hill, Andrei Moiseenko, Justino Zeballos, Lidiia Panaiotti, Luis Hurtado, Reacct Collaborative, Jose Gellona, Miguel Pera, Eloy Espin, Julio Mayol, Marius Kryzauskas, Matteo Frasson, Roel Hompes, Caterina Allmer, Ahmer A. Karimuddin, Matthias Turina, Rumana Islam, Brendan Bebington, Koji Okabayashi, Anastasia Novikova, Alexei Petrov, David A. Clark, Anna Martling, Toni T. Seppälä, Paris Tekkis, Sameh Hany Emile, Tomas Poskus, Guilherme Pagin São Julião, Heather Pringle, Hidde M. Kroon, Bruna B Vailati, Ida Gutlic, Konosuke Moritani, Klaus E. Matzel, Suk Hwan Lee, Paolo Delrio, Martin Mitteregger, S. K. Efetov, Hwee-Hoon Chew, Michael Hoffmeister, Andrea Álvarez, Brodie Elliot, Biniam Teklay, Irmgard Kronberger, Hartwig Kørner, Stephanie Guillon, Emma Greenwood, Dimitri Christoforidis, Gabriela Möslein, Cornelis Verhoef, Adam Dziki, Frank Pfeffer, Alejandro Solis, Frank A. Frizelle, Kyle G. Cologne, Adam Boutall, Miranda Kusters, S. D. Wexner, Kieran Sheahan, Helene Maillou-Martinaud, Laura D’Allens, Leandro Siragusa, Alexis Ulrich, Marta Climent, Joep Knol, Mehrenah Dorna Jafari, Jacobus W A Burger, Jianping Gong, Stefan Morarasu, André D'Hoore, Des Winter, Misael Ocares, Nuno Figueiredo, Stefan Riss, Caterina Foppa, Christiane Bruns, Antonino Spinelli, Homero Rodriguez-Zentner, Katrina Knight, Tarik Sammour, Quentin Denost, Marta Jiménez-Toscano, Yukihide Kanemitsu, Zaher Lakkis, Daniel Duek, Guiseppe S Sica, Anton Berdinskikh, Michael J. Stamos, Michael Deutsch, and REACCT Collaborative
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Oncology ,Adult ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,FEATURES ,UNITED-STATES ,Disease ,030230 surgery ,INCREASING INCIDENCE ,03 medical and health sciences ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,AGE ,SDG 3 - Good Health and Well-being ,Risk Factors ,Internal medicine ,YOUNG-ADULTS ,medicine ,Genetic predisposition ,Adjuvant therapy ,Humans ,Age of Onset ,Neoadjuvant therapy ,RECTAL-CANCER ,Colorectal Neoplasms/epidemiology ,Colorectal Neoplasms/pathology ,Incidence ,Middle Aged ,RISK ,ddc:617 ,business.industry ,LYNCH SYNDROME ,GUT MICROBIOTA ,Cancer ,Correction ,ADENOCARCINOMA ,medicine.disease ,Lynch syndrome ,3. Good health ,Settore MED/18 ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Surgery ,business ,Colorectal Neoplasms - Abstract
Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.
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- 2021
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16. Surgical management of complex ileocolonic Crohn's disease: a survey of IBD colorectal surgeons to assess variability in operative strategy
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Francesco Selvaggi, Álvaro García-Granero, Janindra Warusavitarne, E. Espin, E Garofalo, Mark Coleman, Gianluca Pellino, Michele Carvello, Mick Harper, K Flashman, Valerio Celentano, Matteo Frasson, Nicola de’Angelis, Antonino Spinelli, Garofalo, E, Selvaggi, F, Spinelli, A, Pellino, G, Flashman, K, Frasson, M, Carvello, M, De'Angelis, N, Garcia-Granero, A, Harper, M, Warusavitarne, J, Coleman, M, Espin, E, Celentano, V, Institut Català de la Salut, [Garofalo E] Department of General Surgery, Sant’Andrea Hospital, La Sapienza University, Rome, Italy. [Selvaggi F, Pellino G] Department of Advanced Medical and Surgical Sciences, Universitádella Campania 'Luigi Vanvitelli', Naples, Italy. [Spinelli A] Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Milan, Italy. IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy. [Flashman K] Colorectal Unit, Queen Alexandra Hospital – Portsmouth Hospitals NHS Trust, Portsmouth, UK. [Frasson M] Department of General Surgery, Colorectal Unit, La Fe University and Polytechnic Hospital, University of Valencia, Valencia, Spain. [Espin E] Servei de Cirurgia General, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Laparoscopic surgery ,Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Crohn’s disease ,medicine.medical_specialty ,Crohn, Malaltia de - Cirurgia ,Short Communication ,medicine.medical_treatment ,Ileocaecal resection ,Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases::Crohn Disease [DISEASES] ,Qüestionaris ,Colorectal Neoplasm ,Anastomosis ,Subspecialty ,Inflammatory bowel disease ,03 medical and health sciences ,Ileostomy ,Colorectal surgery, Crohn’s disease, Ileocaecal resection, Inflammatory bowel disease, Laparoscopic surgery ,0302 clinical medicine ,Crohn Disease ,Colorectal surgery ,Surveys and Questionnaires ,medicine ,Humans ,Surveys and Questionnaire ,Surgeons ,Crohn's disease ,business.industry ,General surgery ,Inflammatory Bowel Disease ,Gastroenterology ,Correction ,Otros calificadores::Otros calificadores::/cirugía [Otros calificadores] ,técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Inflammatory Bowel Diseases ,medicine.disease ,digestive system diseases ,Other subheadings::Other subheadings::/surgery [Other subheadings] ,enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal::enfermedad de Crohn [ENFERMEDADES] ,Dissection ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Terapèutica - Presa de decisions ,Colorectal Neoplasms ,business ,Human - Abstract
Introduction To explore the reported variability in the surgical management of ileocolonic Crohn’ s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn’s disease. Methods Anonymous videos demonstrating the small bowel walkthrough and anonymised patients’ clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. Results Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. Conclusions The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy.
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- 2021
17. Inflammatory bowel disease patients requiring surgery can be treated in referral centres regardless of the COVID-19 status of the hospital: results of a multicentric European study during the first COVID-19 outbreak (COVID-Surg)
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Piergiorgio Danelli, Gianluca M. Sampietro, Jorge Sancho-Muriel, Yves Panis, Matteo Rottoli, Caterina Baldi, Christos Kontovounisios, Valerio Celentano, Gilberto Poggioli, Caterina Foppa, Francesco Colombo, Paris P. Tekkis, Michele Carvello, A. Frontali, Matteo Frasson, Antonino Spinelli, Gianluca Pellino, Marta Tanzanu, Rottoli, Matteo, Pellino, Gianluca, Tanzanu, Marta, Baldi, Caterina, Frontali, Alice, Carvello, Michele, Foppa, Caterina, Kontovounisios, Christo, Tekkis, Pari, Colombo, Francesco, Sancho-Muriel, Jorge, Frasson, Matteo, Danelli, Piergiorgio, Celentano, Valerio, Spinelli, Antonino, Panis, Yve, Sampietro, Gianluca M, and Poggioli, Gilberto
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medicine.medical_specialty ,Referral ,Coronavirus disease 2019 (COVID-19) ,Disease ,Logistic regression ,Inflammatory bowel disease ,Hospital ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Referral and Consultation ,Disease Outbreak ,business.industry ,Outbreak ,COVID-19 ,Odds ratio ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Surgery ,Europe ,030220 oncology & carcinogenesis ,Original Article ,030211 gastroenterology & hepatology ,business ,Human - Abstract
Outcomes of inflammatory bowel disease (IBD) patients requiring surgery during the outbreak of Coronavirus disease 19 (COVID-19) are unknown. Aim of this study was to analyse the outcomes depending on the COVID-19 status of the centre. Patients undergoing surgery in six COVID-19 treatment and one COVID-free hospitals (five countries) during the first COVID-19 peak were included. Variables associated with risk of moderate-to-severe complications were identified using logistic regression analysis. A total of 91 patients with Crohn’s disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in one of the COVID-19-treatment hospitals, while 25 (27.5%) in the COVID-19-free centre. More COVID-19-treatment patients required urgent surgery (48.4% vs. 24%, p = 0.035), did not discontinue biologic therapy (15.1% vs. 0%, p = 0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p = 0.0033), and required intensive care admission (10.6% vs. 0%, p = 0.032). Three patients (4.6%) had a SARS-CoV-2 infection postoperatively. Postoperative complications were associated with the use of steroids at surgery (Odds ratio [OR] = 4.10, 95% CI 1.14–15.3, p = 0.03), presence of comorbidities (OR = 3.33, 95% CI 1.08–11, p = 0.035), and Crohn’s disease (vs. ulcerative colitis, OR = 3.82, 95% CI 1.14–15.4, p = 0.028). IBD patients can undergo surgery regardless of the COVID-19 status of the referral centre. The risk of SARS-CoV-2 infection should be taken into account. Supplementary Information The online version contains supplementary material available at 10.1007/s13304-021-01119-y.
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- 2021
18. Correction to: Surgical treatment of colonic Crohn's disease: a national snapshot study
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Gianluca M. Sampietro, Serena Perotti, A Geccherle, Andrea Braini, Mariano Cesare Giglio, Anna Maffioli, Antonino Spinelli, Valerio Celentano, Diego Sasia, Andrea Resegotti, Omar Ghazouani, Enrico Marrano, Angela Variola, Lucio Selvaggi, Marta Cricchio, G. Delaini, Marta Tanzanu, G Vescio, F. Sionne, Luigi Boni, Fiorenzo Botti, G. Rizzo, Andrea Pietrabissa, Claudio Coco, Gloria Zaffaroni, Roberto Peltrini, Ferdinando Ficari, Marco E. Allaix, Harmony Impellizzeri, Lucia Romano, A. Bondurri, Gaetano Gallo, Matteo Rottoli, Gaetano Luglio, Giacomo Calini, Giuseppe S. Sica, Giovanni Terrosu, M. Prati, Andrea Manfreda, Gilberto Poggioli, Luigi Pugliese, Giulia Lamperti, Ludovica Vacca, Michele Carvello, Francesca Paola Tropeano, Luigi Bucci, Francesco Colombo, Michela Mineccia, Diego Foschi, Matteo Sacchi, Imerio Angriman, Giovanni Bordignon, Luigi Zorcolo, Francesco Selvaggi, Angelo Restivo, Raffaele Galleano, Stefania Martorana, Gianluigi Moretto, Giorgio Maria Paolo Graziano, Marco Migliore, Maria Carmela Giuffrida, Giuseppe Sammarco, Massimiliano Mistrangelo, Guido Sciaudone, Gianluca Pellino, S. Deidda, Francesca Di Candido, Antonio Giuliani, Mirko Di Ruscio, Michela Campanelli, Giuliano Barugola, Francesco Giudici, Celentano, Valerio, Pellino, Gianluca, Rottoli, Matteo, Poggioli, Gilberto, Sica, Giuseppe, Giglio, Mariano Cesare, Campanelli, Michela, Coco, Claudio, Rizzo, Gianluca, Sionne, Francesco, Colombo, Francesco, Sampietro, Gianluca, Lamperti, Giulia, Foschi, Diego, Ficari, Ferdinando, Vacca, Ludovica, Cricchio, Marta, Giudici, Francesco, Selvaggi, Lucio, Sciaudone, Guido, Peltrini, Roberto, Manfreda, Andrea, Bucci, Luigi, Galleano, Raffaele, Ghazouani, Omar, Zorcolo, Luigi, Deidda, Simona, Restivo, Angelo, Braini, Andrea, Di Candido, Francesca, Sacchi, Matteo, Carvello, Michele, Martorana, Stefania, Bordignon, Giovanni, Angriman, Imerio, Variola, Angela, Barugola, Giuliano, Di Ruscio, Mirko, Tanzanu, Marta, Geccherle, Andrea, Tropeano, Francesca Paola, Luglio, Gaetano, Sasia, Diego, Migliore, Marco, Giuffrida, Maria Carmela, Marrano, Enrico, Moretto, Gianluigi, Impellizzeri, Harmony, Gallo, Gaetano, Vescio, Giuseppina, Sammarco, Giuseppe, Terrosu, Giovanni, Calini, Giacomo, Bondurri, Andrea, Maffioli, Anna, Zaffaroni, Gloria, Resegotti, Andrea, Mistrangelo, Massimiliano, Allaix, Marco Ettore, Botti, Fiorenzo, Prati, Matteo, Boni, Luigi, Perotti, Serena, Mineccia, Michela, Giuliani, Antonio, Romano, Lucia, Graziano, Giorgio Maria Paolo, Pugliese, Luigi, Pietrabissa, Andrea, Delaini, Giangaetano, Spinelli, Antonino, and Selvaggi, Francesco
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medicine.medical_specialty ,Colonic Crohn's disease ,business.industry ,Crohn’s disease . Crohn’s colitis . Inflammatory bowel disease . Segmental colectomy . Proctocolectomy . National audit ,General surgery ,Vascular surgery ,Cardiac surgery ,Snapshot (photography) ,Cardiothoracic surgery ,medicine ,Surgery ,business ,Surgical treatment ,Abdominal surgery - Published
- 2021
19. Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer
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Luciana Petti, Stefania Vetrano, Silvio Danese, Antonino Spinelli, Federica Rubbino, Andrea Piontini, Giulia Rizzo, Tommaso Cavalleri, Federica Ungaro, Silvia Restelli, Barbara Romano, Alessandro Sgambato, Sudharshan Elangovan, Luigi Laghi, Achille Anselmo, A. Malesci, Michele Carvello, Silvia D'Alessio, Fabio Grizzi, Sanja Štifter, P. Colombo, Vincenzo Arena, Petti, Luciana, Rizzo, Giulia, Rubbino, Federica, Elangovan, Sudharshan, Colombo, Piergiuseppe, Restelli, Silvia, Piontini, Andrea, Arena, Vincenzo, Carvello, Michele, Romano, Barbara, Cavalleri, Tommaso, Anselmo, Achille, Ungaro, Federica, D'Alessio, Silvia, Spinelli, Antonino, Stifter, Sanja, Grizzi, Fabio, Sgambato, Alessandro, Danese, Silvio, Laghi, Luigi, Malesci, Alberto, Vetrano, Stefania, Petti, L., Rizzo, G., Rubbino, F., Elangovan, S., Colombo, P., Restelli, S., Piontini, A., Arena, V., Carvello, M., Romano, B., Cavalleri, T., Anselmo, A., Ungaro, F., D'Alessio, S., Spinelli, A., Stifter, S., Grizzi, F., Sgambato, A., Danese, S., Laghi, L., Malesci, A., and Vetrano, S.
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Adult ,Male ,0301 basic medicine ,Cancer Research ,PTEN ,Colorectal cancer ,Biology ,Malignant transformation ,Mice ,03 medical and health sciences ,Lgr5 ,0302 clinical medicine ,medicine ,Animals ,Humans ,Genes, Tumor Suppressor ,Sphingosine-1-Phosphate Receptors ,Protein kinase B ,S1PR2 ,Aged ,Cell Proliferation ,Aged, 80 and over ,Epithelial proliferation ,Cell growth ,Stem Cells ,Research ,LGR5 ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Pathology ,Epithelial Cells ,Middle Aged ,medicine.disease ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Patologija ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,Stem cell ,Colorectal Neoplasms - Abstract
BackgroundSphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whetherS1PR2participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.MethodsWe screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice.ResultsS1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/minmouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/−mice compared to S1PR2+/+controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.ConclusionsIn normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.Graphical Abstract. Schematic drawing of the role of S1PR2 in normal mucosa and colorectal cancer. In the normal mucosa, S1PR2 is highly expressed by differentiated cells at the upper region of both colon and intestinal crypts (S1PR2 ON), but not by the undifferentiated stem cell at the base of the crypts (S1PR2 OFF), in which acts as a negative proliferative regulator promoting epithelial differentiation. Its loss leads to the expansion of stem cells and reduced levels of PTEN and Axin-2, two negative regulators respectively of PI3K/AKT and Wnt signaling that control β-catenin signaling. The translocation of β-catenin into the nucleus promotes the transcription of target genes involved in the proliferation and malignant transformation. Thereby, S1PR2 works in the intestine as a tumor suppressor
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- 2020
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20. Reduced duration of stay after elective colorectal surgery during the peak phase of COVID-19 pandemic: A positive effect of infection risk awareness?
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Isacco Montroni, Francesco Pasini, Caterina Foppa, Giovanni Taffurelli, Francesco Maria Carrano, Giampaolo Ugolini, Michele Carvello, and Antonino Spinelli
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Male ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Referral ,030230 surgery ,Group A ,Patient Readmission ,Article ,Group B ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pandemic ,medicine ,Humans ,Elective surgery ,Aged ,Aged, 80 and over ,business.industry ,Outbreak ,COVID-19 ,Length of Stay ,Middle Aged ,Colorectal surgery ,030220 oncology & carcinogenesis ,Surgery ,Female ,business ,Enhanced Recovery After Surgery ,Colorectal Surgery - Abstract
Background While during the Covid-19 pandemic elective surgery was shut-down of in most settings, some referral centers were designated as surgery hubs. We sought to investigate how the pandemic scenario hasve impacted the quality of a long-established enhanced recovery protocol (ERP) colorectal surgery (CRS) program in two referral center, designated as colorectal surgery hub, located in the epicentral Italian regions hardest hit by the pandemic. Methods We have compared short-term outcomes of patients undergoing major colorectal surgery with a long-established ERP during the COVID-19 outbreak (group A) with the correspondent timeframe of 2019 (group B). Primary outcomes were morbidity and mortality, LOS, and readmission rate. Results Hundred and thirty-six patients underwent major colorectal surgery in group A and 173 in group B. Post-operative complications and readmission rate were comparable between the two groups. Oncologic case-log was predominant in group A comparing with group B (73.5 vs 61%, p=0.01). A significantly shorter overall LOS was found in group A (p, Elective colorectal surgery, under special precautionary measures, can be safely undertaken with reasonable outcome during COVID 19 pandemic. The empowered infection risk awareness may promote patients engagement with enhanced recovery protocol leading to a significative reduction of the postoperative length of stay.
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- 2020
21. A comparative cost analysis of transanal and laparoscopic total mesorectal excision for rectal cancer
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Marco Montorsi, Annalisa Maroli, Antonino Spinelli, Isacco Montroni, Francesca Di Candido, Roel Hompes, Matteo Sacchi, Michele Carvello, Deborah S. Keller, Elena Vanni, and Surgery
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Male ,medicine.medical_specialty ,Colorectal cancer ,Patient demographics ,Transanal total mesorectal excision (taTME) ,Perioperative Care ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Cost analysis ,Laparoscopic total mesorectal excision (lapTME) ,medicine ,Blood test ,Humans ,Total mesorectal excision (TME) ,Rectal cancer ,Laparoscopy ,Digestive System Surgical Procedures ,Aged ,medicine.diagnostic_test ,business.industry ,Rectal Neoplasms ,Postoperative complication ,Length of Stay ,Middle Aged ,medicine.disease ,Total mesorectal excision ,Surgery ,Treatment Outcome ,030220 oncology & carcinogenesis ,Rectal cancer surgery ,Costs and Cost Analysis ,Health Resources ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Despite proven clinical benefits in the short term, technical difficulties limit utilization of laparoscopy in rectal cancer surgery (RCS). Transanal Total Mesorectal Excision (taTME) overcomes many technical limitations of laparoscopic RCS. However, the costs of this procedure have not been addressed yet. Our goal was to perform a comparative cost analysis of taTME and laparoscopic TME (lapTME). Consecutive patients undergoing curative TME between 1 February 2014 and 31 October 2018 were selected from a prospectively maintained database and stratified, according to the type of procedure, into taTME and lapTME groups. Patient demographics, tumour characteristics, operative parameters, and short-term outcomes were analyzed. The main outcome measure was intraoperative costs of the two procedures. Secondary outcomes were short-term outcome and the utilization of hospital resources to manage the postoperative course. Hundred and fifty-two patients with rectal cancer (66 lapTME, 86 taTME) were included in the study. Surgical supplies required for taTME procedure exceeded the cost of lapTME of 754,54 €. The duration of surgery was not significantly different between the two approaches (266 ± 92.85 vs 271 ± 83.63, p = 0.50). Short-term outcomes were comparable including postoperative complication rate (17 vs 20%, p = 0.68), reintervention rate, and length of stay. There was no difference in hospital resources utilization to manage postoperative course including blood test, diagnostics, consultations, and medications. TaTME has higher intraoperative costs in terms of supplies with respect to lapTME. Short-term outcomes and hospital resources to manage postoperative course are comparable.
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- 2020
22. Laparoscopic derotation of a twisted pouch and redo ileal pouch-anal anastomosis - a video vignette
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Caterina Foppa, F. Piccoli, Antonino Spinelli, C. Bonifacio, Francesco Maria Carrano, and Michele Carvello
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medicine.medical_specialty ,business.industry ,Anastomosis, Surgical ,Proctocolectomy, Restorative ,Gastroenterology ,Anal Canal ,Colonic Pouches ,Surgery ,Ileal Pouch Anal Anastomosis ,Treatment Outcome ,Vignette ,Medicine ,Humans ,Colitis, Ulcerative ,Laparoscopy ,Pouch ,business - Published
- 2020
23. The Management of the Hospitalized Ulcerative Colitis Patient: the Medical–Surgical Conundrum
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Marcin Włodarczyk, Joseph Watfah, Michele Carvello, and Antonino Spinelli
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Toxic megacolon ,medicine.medical_specialty ,medicine.medical_treatment ,Perforation (oil well) ,Anti-Inflammatory Agents ,Disease ,Inflammatory bowel disease ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Gastrointestinal Agents ,Humans ,Medicine ,Intensive care medicine ,Glucocorticoids ,Colectomy ,Patient Care Team ,Proctectomy ,business.industry ,Mortality rate ,Gastroenterology ,Disease Management ,General Medicine ,medicine.disease ,Ulcerative colitis ,Hospitalization ,030220 oncology & carcinogenesis ,Colitis, Ulcerative ,030211 gastroenterology & hepatology ,business ,Complication ,Colorectal Surgery - Abstract
In this study, we present the evidence-based management for patients hospitalized for ulcerative colitis (UC) with a special focus on the synergic approach of the two key actors of the inflammatory bowel disease multidisciplinary team (IBD-MDT): gastroenterologist and surgeon. Focused treatment by a specialized IBD-MDT and early involvement of the colorectal surgeon in the management of hospitalized UC patients is advocated. The colectomy rate has not changed over the years. Moreover, delayed surgery after admission is burden by increase complication and mortality rates. Thus, it is pivotal to identify the patients who are likely to undergo surgery, by mean of predictors of outcome, and not to prolong ineffective medical treatment. The perfect timing based on clinical close monitoring is crucial. Up to 25% of patients with ulcerative colitis (UC) may require hospitalization. The aim of admission is to evaluate severity of the disease, exclude infections and establish proper treatment while monitoring the response. During admission, the patient has to be closely observed for the possible development of toxic megacolon or perforation, which should prompt emergency colectomy. Up to 30% of UC patients will fail to respond to initial intravenous corticosteroid. Non-responder or partial responder to medical therapy should be evaluated for timely surgery or could be considered for rescue medical therapy.
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- 2020
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24. Transanal transection and single‐stapled anastomosis for ileo‐anal pouch surgery – a video vignette
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Matteo Sacchi, Francesco Maria Carrano, Michele Carvello, Antonino Spinelli, and Caterina Foppa
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Stapled anastomosis ,medicine.medical_specialty ,Vignette ,Ileum ,business.industry ,Anastomosis, Surgical ,Gastroenterology ,Anal Canal ,Humans ,Medicine ,business ,Ileo-anal pouch ,Surgery - Published
- 2021
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25. P145 Inflammatory Bowel Disease patients requiring surgery can be treated in referral centres regardless of the COVID-19 status of the hospital: results of a multicentric European study during the first COVID-19 outbreak (COVIBD-Surg)
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Yves Panis, Christos Kontovounisios, Piergiorgio Danelli, Antonino Spinelli, Francesco Colombo, Marta Tanzanu, Matteo Rottoli, Michele Carvello, Paris P. Tekkis, A. Frontali, Gilberto Poggioli, Jorge Sancho-Muriel, Caterina Foppa, Valerio Celentano, F Matteo, C Baldi, Gianluca Pellino, and Giuseppe Sampietro
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medicine.medical_specialty ,Crohn's disease ,Referral ,business.industry ,Gastroenterology ,Outbreak ,General Medicine ,Disease ,medicine.disease ,Clinical: Diagnosis and Outcome ,Comorbidity ,Ulcerative colitis ,Inflammatory bowel disease ,Poster presentations ,Surgery ,Intensive care ,medicine ,business ,AcademicSubjects/MED00260 - Abstract
Background Little is known regarding the outcomes of inflammatory bowel disease (IBD) patients who required surgery during the outbreak of Coronavirus disease 19 (COVID-19). This study aimed to compare outcomes of IBD patients undergoing surgery in COVID-19-treatment and COVID-19-free hospitals. Methods Retrospective study involving patients undergoing IBD surgery in seven centres (six COVID-19-treatment hubs and one COVID-free hospital) across 5 European countries during the period of highest reduction of elective activity due to the first peak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Predictive variables of the risk of moderate-to-severe postoperative complications were analysed using logistic regression analysis. Considering the large number of regressors and the risk of over-fitting due to the small number of events, the least absolute shrinkage and selection operator (LASSO) method was used. Results Of the 91 patients (59 males, 64.8%) with Crohn’s disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in a COVID-19-treatment hospital, while 25 (27.5%) were treated in the COVID-19-free centre. A higher proportion of COVID-19-treatment patients required urgent surgery (48.4% vs 24%, p=0.035), did not discontinue the biologic therapy (15.1% vs. 0%, p=0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p=0.0033), and were admitted to intensive care postoperatively (10.6% vs. 0%, p=0.032). Three patients (4.6%) of the COVID-19-treatment group had a SARS-CoV-2 infection during the hospital course. Use of steroids at surgery (Odds ratio [OR]=4.10, 95% CI 1.14–15.3, p=0.03), presence of comorbidities (OR=3.33, 95% CI 1.08–11, p=0.035), and Crohn’s disease (vs. ulcerative colitis, OR=3.82, 95% CI 1.14–15.4, p=0.028) were associated with risk of moderate-to-severe postoperative complications. The admission to a COVID-19-treatment hospital was not associated with higher risks of complications (OR 2.06, 95% CI 0.54–10.4, p=0.30) Conclusion Although a SARS-CoV-2 infection in the postoperative period represented a concrete risk in IBD patients undergoing surgery in COVID-19-treatment hospitals, the study showed that IBD patients can undergo surgery regardless of the COVID-19-status of the referral centre. The study also showed the lack of standardized practice for IBD patients requiring surgery during the COVID-19 outbreak.
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- 2021
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26. NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer
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Marco Klinger, Stefania Vetrano, Biagio Di Lorenzo, Michele Carvello, Anna Villa, Marita Bosticardo, Silvio Danese, Massimo Roncalli, Francesco Dieli, Antonino Spinelli, Elena Bruni, Ileana Bortolomai, Alessandra Roberto, Matteo Sacchi, Bruno Silva-Santos, Immo Prinz, Federico Colombo, Ferdinando Oriolo, Elena Lo Presti, Paola Spaggiari, Giovanni Cugini, Emanuela Marcenaro, Giovanni Colombo, Joanna Mikulak, Sarina Ravens, Serena Meraviglia, Domenico Mavilio, Silvia Della Bella, Mikulak, Joanna, Oriolo, Ferdinando, Bruni, Elena, Roberto, Alessandra, Colombo, Federico S, Villa, Anna, Bosticardo, Marita, Bortolomai, Ileana, Lo Presti, Elena, Meraviglia, Serena, Dieli, Francesco, Vetrano, Stefania, Danese, Silvio, Della Bella, Silvia, Carvello, Michele M, Sacchi, Matteo, Cugini, Giovanni, Colombo, Giovanni, Klinger, Marco, Spaggiari, Paola, Roncalli, Massimo, Prinz, Immo, Ravens, Sarina, di Lorenzo, Biagio, Marcenaro, Emanuela, Silva-Santos, Bruno, Spinelli, Antonino, and Mavilio, Domenico
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0301 basic medicine ,Male ,Colorectal cancer ,Immunotherapy, Adoptive ,Mice ,0302 clinical medicine ,Sex Hormone-Binding Globulin ,Cytotoxic T cell ,Antigens, Ly ,Intestinal Mucosa ,Intraepithelial Lymphocytes ,Innate immunity ,Aged, 80 and over ,Gastroenterology ,Age Factors ,Receptors, Antigen, T-Cell, gamma-delta ,General Medicine ,Middle Aged ,Phenotype ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Colorectal Neoplasms ,Research Article ,Adult ,Colon ,T cell ,Immunology ,T cells ,Biology ,digestive system ,03 medical and health sciences ,Young Adult ,Ileum ,medicine ,Animals ,Humans ,Aged ,Neoplasm Staging ,Tumor microenvironment ,Innate immune system ,Natural Cytotoxicity Triggering Receptor 1 ,medicine.disease ,030104 developmental biology ,Cancer research ,Intraepithelial lymphocyte ,Homing (hematopoietic) ,T-Lymphocytes, Cytotoxic - Abstract
γδ T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent anti-tumor activities. However, little is known about their origin, phenotype and clinical relevance in colorectal cancer (CRC). To determine γδ IEL gut-specificity, homing and functions, γδ T cells were purified from human healthy blood, lymph nodes, liver, skin, intestine either disease-free or affected by CRC or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a new subset of cytotoxic Vδ1 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46pos/Vδ1 IELs depends both on distinctive features of Vδ1 thymic precursors and gut-environmental factors. Either the constitutive presence of NKp46 on tissue-resident Vδ1 intestinal IELs or its induced-expression on IL-2/IL-15 activated Vδ1 thymocytes are associated with anti-tumor functions. Higher frequencies of NKp46pos/Vδ1 IELs in tumor-free specimens from CRC patients correlate with a lower risk of developing metastatic III/IV disease stages. Additionally, our in vitro settings reproducing CRC tumor-microenvironment inhibited the expansion of NKp46pos/Vδ1 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46pos/Vδ1 IELs able to infiltrate CRC, thus providing new insights to either follow-up cancer progression or develop novel adoptive cellular therapies.
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- 2019
27. GOSAFE - Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery: early analysis on 977 patients
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Barbara Frezza, Giampaolo Castagnoli, Genoveffa Balducci, Valentina Riggio, G. Ugolini, Antonio Arroyo, Gianluca Garulli, Caterina Foppa, Kristin Cardin, Matthijs Plas, Gaetano Gallo, Francesca De Lucia, Francisco López-Rodríguez, Sandra Lario, Franco De Cian, Flavia Foca, Alberto Realis Luc, Paola Tramelli, Roberta Pellegrino, Giacomo Sermonesi, Stefano Sfondrini, Federico Ghignone, Orestis Ioannidis, Nicole M. Saur, Michael David Fejka, Basilio Pirrera, Bruno Alampi, Siri Rostoft, Sam Fox, Chiara Zingaretti, Ingeborg Flåten Backe, Alessandro Spaziani, Barbara Perenze, Minas Baltatzis, Riccardo A. Audisio, Claudia Santos, Luigi Marano, Mariann Lønn, Stefano Scabini, Andrea Massobrio, Patrizio Capelli, Isacco Montroni, Luis E. De León, Cristina Lillo, Alessio Lucarini, Valerio Belgrano, Antonino Spinelli, Daniela Di Pietrantonio, Nicola de Liguori Carino, Davide Pertile, Luigi Conti, Andrea Romboli, Giuseppe Sammarco, Hanoch Kashtan, Baha Siam, Michael T. Jaklitsch, Arild Nesbakken, Michele De Simone, Oriana Nanni, Filippo Banchini, Ajith K. Siriwardena, Giorgio Ercolani, Pietro Achilli, Davide Zattoni, Bernadette Vertogen, Steven D. Wexner, Laura Frain, Konstantinos Galanos-Demiris, Dario Maggioni, Baruch Brenner, Gerardo Palmieri, Giovanni Taffurelli, Barbara L. van Leeuwen, Manuela Albertelli, Gianluca Pellino, Anthony Chan, Alberto Bartoli, Emanuela Stratta, Mario Trompetto, Anna Garutti, Francesca Tauceri, Michele Mazzola, Beatrice Palermo, G. Clerico, Jakub Kenig, Yochai Levy, Graziana Barile, Vincenzo Alagna, Giulio Mari, Roberto Eggenhöffner, Joshua I. S. Bleier, Giovanni Ferrari, Andrea Costanzi, Michele Carvello, Francesca Di Candido, Francesco Monari, Ponnandai Somasundar, Kinga Szabat, Matteo Sacchi, Luis Sánchez-Guillén, Lydia Loutzidou, Lisa Cooper, Hanneke van der Wal-Huisman, Mariateresa Mirarchi, Domenico Soriero, Raffaele De Luca, Andrea Lucchi, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Montroni I., Rostoft S., Spinelli A., Van Leeuwen B.L., Ercolani G., Saur N.M., Jacklitsh M.T., Somasundar P.S., de Liguori Carino N., Ghignone F., Foca F., Zingaretti C., Audisio R.A., Ugolini G., Garutti A., Taffurelli G., Zattoni D., Tramelli P., Sermonesi G., Di Candido F., Carvello M., Sacchi M., De Lucia F., Foppa C., Plas M., Van der Wal-Huisman H., Tauceri F., Perenze B., Di Pietrantonio D., Mirarchi M., Fejka M., Bleier J.I.S., Frain L., Fox S.W., Cardin K., De Leon L.E., Baltatzis M., Chan A.K.C., Siriwardena A.K., Vertogen B., Nanni O., Garulli G., Alagna V., Pirrera B., Lucchi A., Monari F., Conti L., Capelli P., Romboli A., Palmieri G., Banchini F., Marano L., Spaziani A., Castagnoli G., Bartoli A., Trompetto M., Gallo G., Luc A.R., Clerico G., Sammarco G., De Luca R., Barile G., Simone M., Costanzi A., Mari G., Maggioni M., Pellegrino R., Riggio V., Kenig J., Szabat K., Scabini S., Pertile D., Stratta E., Massobrio A., Soriero D., Nesbakken A., Lonn M., Backe I.F., Ferrari G., Mazzola M., Alampi B.D.A., Achilli P., Sfondrini S., Ioannidis O., Loutzidou L., Galanos-Demiris K., Pellino G., Balducci G., Frezza B., Lucarini A., Santos C., Cooper L., Siam B., Levy Y., Brenner B., Kashtan H., Belgrano V., De Cian F., Palermo B., Eggenhoffner R., Albertelli M., Sanchez-Guillen L., Arroyo A., Lopez-Rodriguez F., Lario S., Lillo C., Wexner S.D., Montroni, I., Rostoft, S., Spinelli, A., Van Leeuwen, B. L., Ercolani, G., Saur, N. M., Jacklitsh, M. T., Somasundar, P. S., de Liguori Carino, N., Ghignone, F., Foca, F., Zingaretti, C., Audisio, R. A., Ugolini, G., Garutti, A., Taffurelli, G., Zattoni, D., Tramelli, P., Sermonesi, G., Di Candido, F., Carvello, M., Sacchi, M., De Lucia, F., Foppa, C., Plas, M., Van der Wal-Huisman, H., Tauceri, F., Perenze, B., Di Pietrantonio, D., Mirarchi, M., Fejka, M., Bleier, J. I. S., Frain, L., Fox, S. W., Cardin, K., De Leon, L. E., Baltatzis, M., Chan, A. K. C., Siriwardena, A. K., Vertogen, B., Nanni, O., Garulli, G., Alagna, V., Pirrera, B., Lucchi, A., Monari, F., Conti, L., Capelli, P., Romboli, A., Palmieri, G., Banchini, F., Marano, L., Spaziani, A., Castagnoli, G., Bartoli, A., Trompetto, M., Gallo, G., Luc, A. R., Clerico, G., Sammarco, G., De Luca, R., Barile, G., Simone, M., Costanzi, A., Mari, G., Maggioni, M., Pellegrino, R., Riggio, V., Kenig, J., Szabat, K., Scabini, S., Pertile, D., Stratta, E., Massobrio, A., Soriero, D., Nesbakken, A., Lonn, M., Backe, I. F., Ferrari, G., Mazzola, M., Alampi, B. D. A., Achilli, P., Sfondrini, S., Ioannidis, O., Loutzidou, L., Galanos-Demiris, K., Pellino, G., Balducci, G., Frezza, B., Lucarini, A., Santos, C., Cooper, L., Siam, B., Levy, Y., Brenner, B., Kashtan, H., Belgrano, V., De Cian, F., Palermo, B., Eggenhoffner, R., Albertelli, M., Sanchez-Guillen, L., Arroyo, A., Lopez-Rodriguez, F., Lario, S., Lillo, C., and Wexner, S. D.
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Geriatric Oncology, Surgical Assessment, Functional Recovery, Pre&postoperative testing, Surgery morbidity, Surgery mortality ,Male ,medicine.medical_specialty ,Surgery morbidity ,MEDLINE ,MULTICENTER ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Pre&postoperative testing ,Quality of life ,aged ,aged, 80 and over ,female ,geriatric assessment ,humans ,male ,neoplasms ,postoperative complications ,prospective studies ,quality of life ,Functional Recovery ,Internal medicine ,Neoplasms ,medicine ,80 and over ,Humans ,030212 general & internal medicine ,Prospective Studies ,Elective surgery ,Geriatric Assessment ,cancer, geriatric, outcome ,Aged ,Aged, 80 and over ,business.industry ,Surgical Assessment ,Cancer ,Functional recovery ,medicine.disease ,CANCER ,Geriatric Oncology ,Surgery mortality ,Oncology ,Geriatric oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Observational study ,Female ,Geriatrics and Gerontology ,business ,Early analysis - Abstract
Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.
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- 2019
28. Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11
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Federica Ungaro, Laurent Peyrin-Biroulet, Marco Rasponi, Valentina Garlatti, Federica Rubbino, Antonino Spinelli, Silvio Danese, Luca Massimino, M. Sacchi, P. Colombo, Giovanni Stefano Ugolini, Michele Carvello, Carmen Correale, Paola Spaggiari, Carlotta Tacconi, Stefania Vetrano, Alberto Malesci, Silvia D'Alessio, Salvatore Spanò, Ungaro, F, Colombo, P, Massimino, L, Ugolini, G, Correale, C, Rasponi, M, Garlatti, V, Rubbino, F, Tacconi, C, Spaggiari, P, Spinelli, A, Carvello, M, Sacchi, M, Spano, S, Vetrano, S, Malesci, A, Peyrin-Biroulet, L, Danese, S, and D'Alessio, S
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Cancer Research ,Stromal cell ,Colorectal cancer ,extracellular matrix ,government.form_of_government ,Cell Culture Techniques ,lymphatic endothelium ,colorectal cancer ,Biology ,Metastasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Cells, Cultured ,Cell Proliferation ,Tumor microenvironment ,matrisome ,Gene Expression Profiling ,Endothelial Cells ,gene expression profile ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Growth Differentiation Factors ,Lymphatic Endothelium ,Lymphatic system ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Bone Morphogenetic Proteins ,Cancer cell ,Disease Progression ,Cancer research ,government ,Caco-2 Cells ,Endothelium, Lymphatic ,Colorectal Neoplasms ,Neoplasm Transplantation - Abstract
Colorectal cancer (CRC) is one of the most malignant tumors worldwide. Stromal cells residing in the tumor microenvironment strongly contribute to cancer progression through their crosstalk with cancer cells and extracellular matrix. Here we provide the first evidence that CRC-associated lymphatic endothelium displays a distinct matrisome-associated transcriptomic signature, which distinguishes them from healthy intestinal lymphatics. We also demonstrate that CRC-associated human intestinal lymphatic endothelial cells regulate tumor cell growth via growth differentiation factor 11, a soluble matrisome component which in CRC patients was found to be associated with tumor progression. Our data provide new insights into lymphatic contribution to CRC growth, aside from their conventional role as conduits of metastasis.
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- 2019
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29. Ileal pouch–anal anastomosis with fluorescence angiography: a case‐matched study
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Annalisa Maroli, Paulo Gustavo Kotze, Marco Montorsi, Isacco Montroni, Frédéric Ris, N Buchs, Antonino Spinelli, and Michele Carvello
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Adult ,Male ,medicine.medical_specialty ,Leak ,Databases, Factual ,Colon ,Anastomotic Leak ,Anastomosis ,law.invention ,chemistry.chemical_compound ,stomatognathic system ,Randomized controlled trial ,Ileum ,law ,Fluorescence angiography ,Humans ,Medicine ,Prospective Studies ,Fluorescein Angiography ,Ligation ,Retrospective Studies ,Familial adenomatous polyposis ,ddc:617 ,business.industry ,Proctocolectomy, Restorative ,Pouch surgery ,Gastroenterology ,Restorative proctocolectomy ,Postoperative complication ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Indocyanine green ,Surgery ,stomatognathic diseases ,Treatment Outcome ,chemistry ,Case-Control Studies ,Female ,Pouch ,business - Abstract
Aim An anastomotic leak in ileoanal pouch surgery may lead to pouch failure. Constructing a tension-free ileal pouch-anal anastomosis (IPAA) reduces this risk but can be technically challenging, balancing pouch vascularization with ileal mesenteric length and site of vessel ligation. Fluorescence angiography (FA) may help the clinician make a more balanced judgement. Methods Thirty-two patients undergoing minimally invasive completion proctectomy with FA-guided IPAA at two academic centres were matched and compared on a 1:1 basis to a historical group undergoing the same procedure without the use of this technique. Results Ligation of the ileocolic vessels was safely performed in 15/32 (47%) of FA patients compared with 5/32 (16%) of historical controls. One patient underwent intra-operative IPAA reconstruction after FA detected ischaemia. No anastomotic leak occurred with FA but there was only one in the historical controls (P = 0.31). The postoperative complication rate was similar between the two groups (P = 0.60). Conclusion FA is applicable to IPAA surgery and may help to reduce perfusion-related anastomotic leaks. A prospective randomized trial is warranted.
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- 2019
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30. Diverticulitis: An Update From the Age Old Paradigm
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Maryam Ilyas, Paul E. Wise, Michelle L Cowan, Jason F. Hall, Karim Alavi, Verity H. Wood, Maria Michailidou, Des C. Winter, Jennifer L Williams, Alexander T. Hawkins, Tamara Glyn, Frank A. Frizelle, C. Tyler Ellis, Gaetano Gallo, Tiffany Chan, Antonino Spinelli, Adil Khan, Janet T. Lee, Scott R. Steele, Michele Carvello, Karen Zaghiyan, Tim Eglinton, Valentine Nfonsam, Danielle Collins, and Amy L. Lightner
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Diagnostic Imaging ,medicine.medical_specialty ,medicine.medical_treatment ,Colonoscopy ,Anastomosis ,Article ,Diverticulitis, Colonic ,unusual location of diverticular disease ,Risk Factors ,medicine ,Humans ,Hernia ,Digestive System Surgical Procedures ,Surgical approach ,Preoperative planning ,medicine.diagnostic_test ,business.industry ,General surgery ,diverticulitis ,epidemiology ,Colostomy ,Age Factors ,Disease Management ,General Medicine ,Diverticulitis ,medicine.disease ,Surgery ,Ureteral Catheters ,business - Abstract
For a disease process that affects so many, we continue to struggle to define optimal care for patients with diverticular disease. Part of this stems from the fact that diverticular disease requires different treatment strategies across the natural history- acute, chronic and recurrent. To understand where we are currently, it is worth understanding how treatment of diverticular disease has evolved. Diverticular disease was rarely described in the literature prior to the 1900’s. In the late 1960’s and early 1970’s, Painter and Burkitt popularized the theory that diverticulosis is a disease of Western civilization based on the observation that diverticulosis was rare in rural Africa but common in economically developed countries. Previous surgical guidelines focused on early operative intervention to avoid potential complicated episodes of recurrent complicated diverticulitis (e.g., with free perforation) that might necessitate emergent surgery and stoma formation. More recent data has challenged prior concerns about decreasing effectiveness of medical management with repeat episodes and the notion that the natural history of diverticulitis is progressive. It has also permitted more accurate grading of the severity of disease and permitted less invasive management options to attempt conversion of urgent operations into the elective setting, or even avoid an operation altogether. The role of diet in preventing diverticular disease has long been debated. A high fiber diet appears to decrease the likelihood of symptomatic diverticulitis. The myth of avoid eating nuts, corn, popcorn, and seeds to prevent episodes of diverticulitis has been debunked with modern data. Overall, the recommendations for “diverticulitis diets” mirror those made for overall healthy lifestyle – high fiber, with a focus on whole grains, fruits and vegetables. Diverticulosis is one of the most common incidental findings on colonoscopy and the eighth most common outpatient diagnosis in the United States. Over 50% of people over the age of 60 and over 60% of people over age 80 have colonic diverticula. Of those with diverticulosis, the lifetime risk of developing diverticulitis is estimated at 10–25%, although more recent studies estimate a 5% rate of progression to diverticulitis. Diverticulitis accounts for an estimated 371,000 emergency department visits and 200,000 inpatient admissions per year with annual cost of 2.1–2.6 billion dollars per year in the United States. The estimated total medical expenditure (inpatient and outpatient) for diverticulosis and diverticulitis in 2015 was over 5.4 billion dollars. The incidence of diverticulitis is increasing. Besides increasing age, other risk factors for diverticular disease include use of NSAIDS, aspirin, steroids, opioids, smoking and sedentary lifestyle. Diverticula most commonly occur along the mesenteric side of the antimesenteric taeniae resulting in parallel rows. These spots are thought to be relatively weak as this is the location where vasa recta penetrate the muscle to supply the mucosa. The exact mechanism that leads to diverticulitis from diverticulosis is not definitively known. The most common presenting complaint is of left lower quadrant abdominal pain with symptoms of systemic unwellness including fever and malaise, however the presentation may vary widely. The gold standard cross-sectional imaging is multi-detector CT. It is minimally invasive and has sensitivity between 98% and specificity up to 99% for diagnosing acute diverticulitis. Uncomplicated acute diverticulitis may be safely managed as an out-patient in carefully selected patients. Hospitalization is usually necessary for patients with immunosuppression, intolerance to oral intake, signs of severe sepsis, lack of social support and increased comorbidities. The role of antibiotics has been questioned in a number of randomized controlled trials and it is likely that we will see more patients with uncomplicated disease treated with observation in the future Acute diverticulitis can be further sub classified into complicated and uncomplicated presentations. Uncomplicated diverticulitis is characterized by inflammation limited to colonic wall and surrounding tissue. The management of uncomplicated diverticulitis is changing. Use of antibiotics has been questioned as it appears that antibiotic use can be avoided in select groups of patients. Surgical intervention appears to improve patient’s quality of life. The decision to proceed with surgery is recommended in an individualized manner. Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Abscesses can be treated with percutaneous drainage if the abscess is large enough. The optimal long-term strategy for patients who undergo successful non-operative management of their diverticular abscess remains controversial. There are clearly patients who would do well with an elective colectomy and a subset who could avoid an operation all together however, the challenge is appropriate risk-stratification and patient selection. Management of patients with perforation depends greatly on the presence of feculent or purulent peritonitis, the extent of contamination and hemodynamic status and associated comorbidities. Fistulas and strictures are almost always treated with segmental colectomy. After an episode of acute diverticulitis, routine colonoscopy has been recommended by a number of societies to exclude the presence of colorectal cancer or presence of alternative diagnosis like ischemic colitis or inflammatory bowel disease for the clinical presentation. Endoscopic evaluation of the colon is normally delayed by about 6 weeks from the acute episode to reduce the risk associated with colonoscopy. Further study has questioned the need for endoscopic evaluation for every patient with acute diverticulitis. Colonoscopy should be routinely performed after complicated diverticulitis cases, when the clinical presentation is atypical or if there are any diagnostic ambiguity, or patient has other indications for colonoscopy like rectal bleeding or is above 50 years of age without recent colonoscopy. For patients in whom elective colectomy is indicated, it is imperative to identify a wide range of modifiable patient co-morbidities. Every attempt should be made to improve a patient’s chance of successful surgery. This includes optimization of patient risk factors as well as tailoring the surgical approach and perioperative management. A positive outcome depends greatly on thoughtful attention to what makes a complicated patient “complicated”. Operative management remains complex and depends on multiple factors including patient age, comorbidities, nutritional state, severity of disease, and surgeon preference and experience. Importantly, the status of surgery, elective versus urgent or emergent operation, is pivotal in decision-making, and treatment algorithms are divergent based on the acuteness of surgery. Resection of diseased bowel to healthy proximal colon and rectal margins remains a fundamental principle of treatment although the operative approach may vary. For acute diverticulitis, a number of surgical approaches exist, including loop colostomy, sigmoidectomy with colostomy (Hartmann’s procedure) and sigmoidectomy with primary colorectal anastomosis. Overall, data suggest that primary anastomosis is preferable to a Hartman’s procedure in select patients with acute diverticulitis. Patients with hemodynamic instability, immunocompromised state, feculent peritonitis, severely edematous or ischemic bowel, or significant malnutrition are poor candidates. The decision to divert after colorectal anastomosis is at the discretion of the operating surgeon. Patient factors including severity of disease, tissue quality, and comorbidities should be considered. Technical considerations for elective cases include appropriate bowel preparation, the use of a laparoscopic approach, the decision to perform a primary anastomosis, and the selected use of ureteral stents. Management of the patient with an end colostomy after a Hartmann’s procedure for acute diverticulitis can be a challenging clinical scenario. Between 20 – 50% of patients treated with sigmoid resection and an end colostomy after an initial severe bout of diverticulitis will never be reversed to their normal anatomy. The reasons for high rates of permanent colostomies are multifactorial. The debate on the best timing for a colostomy takedown continues. Six months is generally chosen as the safest time to proceed when adhesions may be at their softest allowing for a more favorable dissection. The surgical approach will be a personal decision by the operating surgeon based on his or her experience. Colostomy takedown operations are challenging surgeries. The surgeon should anticipate and appropriately plan for a long and difficult operation. The patient should undergo a full antibiotic bowel preparation. Preoperative planning is critical; review the initial operative note and defining the anatomy prior to reversal. When a complex abdominal wall closure is necessary, consider consultation with a hernia specialist. Open surgery is the preferred surgical approach for the majority of colostomy takedown operations. Finally, consider ureteral catheters, diverting loop ileostomy, and be prepared for all anastomotic options in advance. Since its inception in the late 90’s, laparoscopic lavage has been recognized as a novel treatment modality in the management of complicated diverticulitis; specifically, Hinchey III (purulent) diverticulitis. Over the last decade, it has been the subject of several randomized controlled trials, retrospective studies, systematic reviews as well as cost-efficiency analyses. Despite being the subject of much debate and controversy, there is a clear role for laparoscopic lavage in the management of acute diverticulitis with the caveat that patient selection is key. Segmental colitis associated with diverticulitis (SCAD) is an inflammatory condition affecting the colon in segments that are also affected by diverticulosis, namely, the sigmoid colon. While SCAD is considered a separate clinical entity, it is frequently confused with diverticulitis or inflammatory bowel disease (IBD). SCAD affects approximately 1.4% of the general population and 1.15 to 11.4% of those with diverticulosis and most commonly affects those in their 6th decade of life. The exact pathogenesis of SCAD is unknown, but proposed mechanisms include mucosal redundancy and prolapse occurring in diverticular segments, fecal stasis, and localized ischemia. Most case of SCAD resolve with a high-fiber diet and antibiotics, with salicylates reserved for more severe cases. Relapse is uncommon and immunosuppression with steroids is rarely needed. A relapsing clinical course may suggest a diagnosis of IBD and treatment as such should be initiated. Surgery is extremely uncommon and reserved for severe refractory disease. While sigmoid colon involvement is considered the most common site of colonic diverticulitis in Western countries, diverticular disease can be problematic in other areas of the colon. In Asian countries, right-sided diverticulitis outnumbers the left. This difference seems to be secondary to dietary and genetic factors. Differential diagnosis might be difficult because of similarity with appendicitis. However accurate imaging studies allow a precise preoperative diagnosis and management planning. Transverse colonic diverticulitis is very rare accounting for less than 1% of colonic diverticulitis with a perforation rate that has been estimated to be even more rare. Rectal diverticula are mostly asymptomatic and diagnosed incidentally in the majority of patients and rarely require treatment. Giant colonic diverticula (GCD) is a rare presentation of diverticular disease of the colon and it is defined as an air-filled cystic diverticulum larger than 4 cm in diameter. The pathogenesis of GCD is not well defined. Overall, the management of diverticular disease depends greatly on patient, disease and surgeon factors. Only by tailoring treatment to the patient in front of us can we achieve optimal outcomes.
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- 2020
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31. With adequate precautions colorectal cancer surgery can be safely continued during COVID-19 pandemic
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Caterina Foppa, Francesco Maria Carrano, Michele Carvello, and Antonino Spinelli
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Infection Control ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,COVID-19 Testing ,Italy ,Risk Factors ,Oncology Service, Hospital ,Colorectal cancer surgery ,Correspondence ,Preoperative Care ,Pandemic ,Humans ,Medicine ,Surgery ,Colorectal Neoplasms ,business ,Intensive care medicine ,Pandemics - Published
- 2020
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32. COMBINED ENDOSCOPIC AND TRANSANAL SURGERY (TASER) FOR THE TREATMENT OF A LARGE RECTAL LESIONS: A CASE-SERIES
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Antonino Spinelli, A. Repici, M. Sacchi, G. David, Elisa Chiara Ferrara, Silvia Carrara, Michele Carvello, Alessandro Fugazza, Roberta Maselli, Rossella Semeraro, Andrea Anderloni, and Piera Alessia Galtieri
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medicine.medical_specialty ,business.industry ,Taser ,medicine ,Transanal surgery ,business ,Surgery - Published
- 2018
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33. Fluorescence angiography during transanal trans-stomal proctectomy and ileal pouch anal anastomosis: a video vignette
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Antonino Spinelli, Michele Carvello, G. David, Matteo Sacchi, Paulo Gustavo Kotze, and Fabrizio Cantore
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medicine.medical_specialty ,genetic structures ,medicine.diagnostic_test ,business.industry ,Fluorescence angiography ,Gastroenterology ,Anal surgery ,Anastomosis ,eye diseases ,Colorectal surgery ,Surgery ,Ileal Pouch Anal Anastomosis ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Angiography ,medicine ,030211 gastroenterology & hepatology ,Pouch ,business ,Perfusion - Abstract
Indocanine green (ICG) fluorescence is able to assess in vivo tissue perfusion. This technique has been validated in colorectal surgery and provides, by real time angiography, the evaluation of bowel perfusion before anastomosis[1]. This video shows the usefulness of ICG fluorescence application in ileal pouch anal surgery. This article is protected by copyright. All rights reserved.
- Published
- 2017
34. First experience in colorectal surgery with a new robotic platform with haptic feedback
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G. David, Isacco Montroni, Antonino Spinelli, Matteo Sacchi, Stefano Gidaro, Marco Montorsi, and Michele Carvello
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medicine.medical_specialty ,medicine.diagnostic_test ,Colorectal cancer ,business.industry ,General surgery ,medicine.medical_treatment ,Gastroenterology ,Perioperative ,Single Center ,medicine.disease ,Colorectal surgery ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Laparotomy ,medicine ,Diverticular disease ,030211 gastroenterology & hepatology ,Robotic surgery ,Laparoscopy ,business - Abstract
The use of robotic techniques is increasing in colorectal surgery. Recently, the Senhance™ surgical robotic system was introduced as a novel robotic platform designed to overcome some of the limits of standard laparoscopy. This study describes the initial, single center experience, evaluating feasibility and safety of the new robotic system in performing colorectal surgical procedures. Methods From June 2015 to November 2016, perioperative data of the first 45 patients who underwent robotic colorectal surgery with the SenhanceTM surgical robotic system were collected and analyzed. Indications for surgery included inflammatory bowel disease, colorectal cancer, endoscopically unresectable adenomas and complicated diverticular disease. Results The median age was 57 years (18-92) and the median BMI was 24 Kg/m2 (16-30). Surgical indications were colorectal cancer (66%), complicated inflammatory bowel disease (18%), diverticular disease (11%) and endoscopically unresectable adenoma (4.4%). The median operative time was 256 minutes; the median docking time 10.7 min (range 2-25). There were 3 conversions to standard laparoscopy, and none to laparotomy. All patients operated on for malignancy (28 adenocarcinoma, 2 neuroendocrine tumors) underwent an appropriate oncological procedure. The median time to discharge was 5 days (range 3-19). The incidence of post-operative complications was 35.5% (Clavien-Dindo I/II-14 patients, III-2 patients). One patient was readmitted in the postoperative period. No patient required reoperation. Conclusion The results of this audit suggest that adoption of The Senhance™ surgical robotic system in colorectal surgery is feasible and safe. More clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques. This article is protected by copyright. All rights reserved.
- Published
- 2017
35. Single port laparoscopic ileocaecal resection for Crohn's disease: a multicentre comparison with multi-port laparoscopy
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Albert Wolthuis, A. D'Hoore, A. de Buck van Overstraeten, M. Sacchi, E. J. de Groof, Antonino Spinelli, Michele Carvello, W. A. Bemelman, Christianne J. Buskens, Other departments, Amsterdam Gastroenterology Endocrinology Metabolism, and Surgery
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Laparoscopic surgery ,Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Operative Time ,Stoma ,03 medical and health sciences ,0302 clinical medicine ,Port (medical) ,Postoperative Complications ,Crohn Disease ,Ileum ,medicine ,Humans ,Laparoscopy ,Cecum ,Digestive System Surgical Procedures ,Pain Measurement ,Retrospective Studies ,Crohn's disease ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Postoperative complication ,Retrospective cohort study ,Length of Stay ,medicine.disease ,Conversion to Open Surgery ,Surgery ,Treatment Outcome ,030220 oncology & carcinogenesis ,Anesthesia ,030211 gastroenterology & hepatology ,Female ,Analgesia ,business ,Body mass index - Abstract
Background and aims Single port (SP) ileocecal resection (ICR) is an established technique but there are no large studies comparing SP and multi-port (MP) laparoscopic surgery in Crohn's disease (CD). The aim of this study was to compare postoperative pain scores and analgesia requirements after SP and MP laparoscopic ICR for CD. Methods This was a retrospective study of patients undergoing SP or MP ICR for CD in three tertiary referral centres from February 1999-October 2014. Baseline characteristics (age, sex, body mass index and indication for surgery) were compared. Primary endpoints were postoperative pain scores, analgesia requirements and short-term postoperative outcomes. Results SP ICR (n=101) and MP ICR (n=156) patients were included in the study. VAS scores were significantly lower after SP ICR on postoperative day 1 (P=0.016) and day 2 (P=0.04). Analgesia requirements were significantly reduced on postoperative day 2 in the SP group compared with MP group (P=0.007). Duration of surgery, conversion to open surgery and stoma rates were comparable between the two groups. Surgery was more complex in terms of additional procedures when MP was adopted (P=0.001). There were no differences in postoperative complication rates, postoperative food intake, length of stay and readmissions. Conclusions This data suggests that in comparison to standard laparoscopic surgery, SP ICR might be less painful and patients require less opioid analgesia. This article is protected by copyright. All rights reserved.
- Published
- 2017
36. MFSD2A Promotes Endothelial Generation of Inflammation-resolving Lipid Mediators and Reduces Colitis in Mice
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Alberto Malesci, Silvio Danese, Antonino Spinelli, Federica Furfaro, Stefania Vetrano, Paola Antonia Corsetto, Luciana Petti, Luca Massimino, Angela Maria Rizzo, Silvia D'Alessio, Laurent Peyrin-Biroulet, Gionata Fiorino, Carlotta Tacconi, Domenico Mavilio, Philippe Fonteyne, Federica Ungaro, F. Calcaterra, Andrea Piontini, Valeria Garzarelli, Silvia Della Bella, Carmen Correale, Krishna Rao Maddipati, Michele Carvello, Ungaro, F., Tacconi, C., Massimino, L., Corsetto, P., Correale, C., Fonteyne, P., Piontini, A., Garzarelli, V., Calcaterra, F., Della Bella, S., Spinelli, A., Carvello, M., Rizzo, A., Vetrano, S., Petti, L., Fiorino, G., Furfaro, F., Mavilio, D., Maddipati, K., Malesci, A., Peyrin-Biroulet, L., D’Alessio, S., and Danese, S.
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0301 basic medicine ,Endothelium ,Docosahexaenoic Acids ,Angiogenesis ,Colon ,IBD ,Mice, Nude ,Inflammation ,Biology ,gut vasculature ,Transfection ,Inflammatory bowel disease ,03 medical and health sciences ,angiogenesis ,Cytochrome P-450 Enzyme System ,inflammatory bowel disease ,medicine ,Animals ,Humans ,Oxylipins ,Progenitor cell ,Colitis ,Cells, Cultured ,Endothelial Progenitor Cells ,Hepatology ,Symporters ,Tumor Necrosis Factor-alpha ,Tumor Suppressor Proteins ,Dextran Sulfate ,Gastroenterology ,Membrane Transport Proteins ,Lipid metabolism ,medicine.disease ,Ulcerative colitis ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Cancer research ,Epoxy Compounds ,RNA Interference ,medicine.symptom ,Signal Transduction - Abstract
Background & Aims Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation. Methods We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate–induced colitis, with or without oral administration of DHA. Results Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors. Conclusions Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis.
- Published
- 2017
37. Psychological Perspectives of Inflammatory Bowel Disease Patients Undergoing Surgery: Rightful Concerns and Preconceptions
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Antonino Spinelli, Michele Carvello, André D'Hoore, and Francesco Pagnini
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medicine.medical_specialty ,Ostomy ,IBD ,Clinical Biochemistry ,Population ,Settore M-PSI/08 - PSICOLOGIA CLINICA ,Inflammatory bowel disease ,Quality of life ,Drug Discovery ,Humans ,Medicine ,education ,Psychiatry ,Depression (differential diagnoses) ,Pharmacology ,Physician-Patient Relations ,education.field_of_study ,Apprehension ,business.industry ,Mental Disorders ,Inflammatory Bowel Diseases ,medicine.disease ,Surgery ,Distress ,Quality of Life ,Molecular Medicine ,Defecation ,Anxiety ,medicine.symptom ,business - Abstract
Surgery has been associated with variable effect on the quality of life of inflammatory bowel disease (IBD) patients, depending on clinical patterns and baseline disease characteristics. However, surgical treatment is often conceived by these patients with distress and considered as the failure of their therapies. Lack of control, risk of complications, defacement of the body image, need of ostomy and hospitalization may be triggering concerns leading to anguish and anxiety. Even though the quality of life in most cases generally improves after surgery, some particular aspects such as sexual activity, bowel movements and the ability to deal with a possible stoma may present a slower amelioration trend. These problems represent common causes of distress and may lead to an heightened risk of depression and anxiety with respect to background population. The psychological impact and apprehension surrounding surgery will be discussed in this review. Pros and cons of the surgical treatment in various IBD populations and its long-term sequelae in terms of quality of life and psychological well-being will be highlighted. Furthermore the tools to encompass these issues such as complete patient information, gastroenterologist/surgeon synergy and psychological counseling will be explored analyzing their respective roles.
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- 2014
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38. Refractory Distal Ulcerative Colitis: Is Proctocolectomy Always Necessary?
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Antonino Spinelli, Marco Montorsi, and Michele Carvello
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medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Rectum ,Gastroenterology ,Left colon ,Refractory ,Risk Factors ,Internal medicine ,Humans ,Medicine ,business.industry ,Proctocolectomy ,Proctocolectomy, Restorative ,General Medicine ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Ileal Pouch Anal Anastomosis ,Treatment Outcome ,medicine.anatomical_structure ,Quality of Life ,Colitis, Ulcerative ,business ,Cancer risk ,Medical therapy - Abstract
Refractory distal ulcerative colitis (RDUC) is defined as persistence of symptoms caused by endoscopically proven colonic inflammation located at the rectum or left colon despite oral/topical steroids and 5-ASA. RDUC affects a small subset of patients and is associated with chronic disabling symptoms and increased social/medical costs. Moreover, patients with long-standing ulcerative colitis (UC) carry an elevated risk of developing colorectal cancer and colonic mucosa high-grade dysplasia. Alternative medical strategies in steroid refractory disease are unlikely to provide durable remission in all patients, carry potential severe side effects and, as immunosuppressants, the risk of other neoplasms, and may increase the short-term complication rate when surgery is finally required. Restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) allows the complete removal of the diseased rectum and colon, virtually eliminating the risk of malignant transformation and reestablishing intestinal continuity with continence preservation. Since the introduction of this surgical procedure, morbidity and mortality rates have been drastically reduced. Despite the still notable rate of surgical complications, long-term quality of life assessment has shown excellent results in nearly all patients who have undergone RP-IPAA, comparing well with the general population. Furthermore, when performed for distal UC, RP-IPAA produces similar surgical outcomes with respect to pancolitis. In conclusion, RP-IPAA should always be considered in patients with RDUC, and multidisciplinary counseling should provide patients clear information about the advantages of surgery and possible complications as well as the chance to achieve disease remission with medical therapy.
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- 2014
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39. Laparoscopic Pouch Excision Combined With Intersphincteric Resection
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G. Clerico, Antonino Spinelli, Nuha A. Yassin, Caterina Foppa, Matteo Sacchi, and Michele Carvello
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Reoperation ,medicine.medical_specialty ,Ileostomy ,business.industry ,Proctocolectomy ,Dissection ,medicine.medical_treatment ,Proctocolectomy, Restorative ,Gastroenterology ,Anal Canal ,General Medicine ,Pouchitis ,Intersphincteric resection ,Surgery ,Postoperative Complications ,Humans ,Medicine ,Colitis, Ulcerative ,Laparoscopy ,Pouch ,business - Published
- 2019
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40. Mesenchymal Stem Cells for Perianal Crohn’s Disease
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Paulo Gustavo Kotze, Amy L. Lightner, Michele Carvello, Takayuki Yamamoto, and Antonino Spinelli
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Crohn’s disease ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,perianal ,Fistula ,Review ,Disease ,Mesenchymal Stem Cell Transplantation ,law.invention ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Randomized controlled trial ,stem cells ,law ,Internal medicine ,medicine ,Animals ,Humans ,Rectal Fistula ,fistula ,lcsh:QH301-705.5 ,Randomized Controlled Trials as Topic ,Perianal Crohn's disease ,Wound Healing ,Crohn's disease ,business.industry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Medicine ,medicine.disease ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Quality of Life ,Stem cell ,business ,Colorectal surgeons - Abstract
Perianal fistulizing Crohn’s disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.
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- 2019
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41. Management and outcome of cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer
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Michele Carvello, Peter S.N. van Rossum, Leonie Haverkamp, Richard van Hillegersberg, and Jelle P. Ruurda
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medicine.medical_specialty ,medicine.diagnostic_test ,Thoracic cavity ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Mediastinum ,Chylothorax ,General Medicine ,030230 surgery ,Esophageal cancer ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Esophagectomy ,030220 oncology & carcinogenesis ,Laparotomy ,medicine ,Thoracoscopy ,medicine.symptom ,business ,Subcutaneous emphysema - Abstract
The aim of this study was to evaluate management strategies and related outcomes for cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer with gastric conduit reconstruction. Patients with esophageal cancer undergoing transthoracic esophagectomy with cervical anastomosis from October 2003 to December 2014 were identified from a prospectively acquired database. Management strategies and related outcomes among patients with anastomotic leakage confined to the neck were compared to patients with intrathoracic manifestation of anastomotic leakage. From a total of 286 patients, leakage of the cervical anastomosis occurred in 60 patients (21%) at a median time of 7 days after esophagectomy. Leakage was confined to the neck in 23 of 60 patients (38%), whereas 37 of 60 patients (62%) presented with intrathoracic spread. Leakages with intrathoracic manifestation were more frequently accompanied by a positive SIRS score compared to leakages confined to the neck (73% vs. 35%, respectively; P = 0.004). Drainage of the anastomotic leakage through the neck wound was effective in all of 23 patients (100%) with cervical manifestation. In patients with intrathoracic manifestation, mediastinal drainage through the neck was successful in 15 of 37 patients (41%), whereas 22 patients (59%) required an intervention through the thoracic cavity. Compared to patients with leakage confined to the neck, patients with intrathoracic manifestation showed prolonged intensive care unit (ICU) stay (median 6 vs. 2 days, respectively; P = 0.001), hospital stay (median 34 vs. 19 days, respectively; P
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- 2016
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42. V.02.2 COMBINED ENDOSCOPIC AND TRANSANAL SURGERY (TASER) FOR THE TREATMENT OF LARGE RECTAL LESIONS: A CASE-SERIES (WITH VIDEO)
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A. Repici, Andrea Anderloni, Alessandro Fugazza, Piera Alessia Galtieri, Michele Carvello, Silvia Carrara, Roberta Maselli, M. Sacchi, Antonino Spinelli, Rossella Semeraro, G. David, and Elisa Chiara Ferrara
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medicine.medical_specialty ,Hepatology ,business.industry ,Taser ,Gastroenterology ,medicine ,Transanal surgery ,business ,Surgery - Published
- 2018
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43. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer
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Federica Marchesi, Marco Erreni, Samantha Pesce, Giuseppe Di Caro, Marco Montorsi, Michele Carvello, Matteo Sacchi, Jelena Todoric, Antonino Spinelli, and Paola Allavena
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0301 basic medicine ,Oncology ,Male ,Colorectal cancer ,Physiology ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Biochemistry ,0302 clinical medicine ,Surgical oncology ,Recurrence ,Immune Physiology ,Medicine and Health Sciences ,Medicine ,Postoperative Period ,Stage (cooking) ,lcsh:Science ,Immune Response ,Innate Immune System ,Multidisciplinary ,Acute-phase protein ,Hematology ,Prognosis ,Body Fluids ,Blood ,030220 oncology & carcinogenesis ,Cytokines ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,Anatomy ,Inflammation Mediators ,Colorectal Neoplasms ,Research Article ,medicine.medical_specialty ,Inflammatory Diseases ,Immunology ,Inflammation ,Surgical and Invasive Medical Procedures ,Blood Plasma ,Proinflammatory cytokine ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,Biomarkers, Tumor ,Humans ,Aged ,Neoplasm Staging ,Colorectal Cancer ,Tumor microenvironment ,business.industry ,lcsh:R ,Cancers and Neoplasms ,Biology and Life Sciences ,Proteins ,Correction ,Acute Phase Proteins ,Molecular Development ,medicine.disease ,030104 developmental biology ,Immune System ,lcsh:Q ,business ,Developmental Biology ,Follow-Up Studies - Abstract
Background Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients. Methods Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0–IV CRC and associated with post-operative disease recurrence. Results Cox multivariate analysis showed that combined high levels (≥ROC cut off-value) of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13–65.1)] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P
- Published
- 2015
44. Suprapubic single port ileocaecal resection for complicated Crohn's disease - a video vignette
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Michele Carvello and Antonino Spinelli
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Ileocaecal resection ,Laparoscopic surgery ,medicine.medical_specialty ,Crohn's disease ,business.industry ,medicine.medical_treatment ,Pelvic mass ,Gastroenterology ,Ileocecal resection ,medicine.disease ,Port (computer networking) ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Vignette ,030220 oncology & carcinogenesis ,medicine ,030211 gastroenterology & hepatology ,In patient ,business - Abstract
Laparoscopic surgery in patients with complex Crohn's disease (CD) can be technically challenging and often necessitates the use of multiple ports or conversion. 1, 2, 3 In this video, we demonstrate our suprapubic single port (SPSP) technique for ileocecal resection (ICR) in a patient with a complex pelvic mass. This article is protected by copyright. All rights reserved.
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- 2017
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45. Correction: Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer
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Samantha Pesce, Giuseppe Di Caro, Federica Marchesi, Antonino Spinelli, Paola Allavena, Michele Carvello, Marco Erreni, Matteo Sacchi, Jelena Todoric, and Marco Montorsi
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Oncology ,medicine.medical_specialty ,Pathology ,Multidisciplinary ,Colorectal cancer ,business.industry ,lcsh:R ,lcsh:Medicine ,medicine.disease ,Marie curie ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,media_common.cataloged_instance ,lcsh:Q ,European union ,lcsh:Science ,business ,030215 immunology ,media_common - Abstract
There is an error in the Funding section. The first sentence should read: The work was supported by 16230 Associazione Italiana per la ricerca sul cancro, Marie Curie Actions European Union to GDC.
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- 2016
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46. 869 A Novel Sierological Inflammatory Score As Possible Prognostic Marker in Colorectal Cancer
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Giuseppe Di Caro, Paola Allavena, Samantha Pesce, Antonino Spinelli, Federica Marchesi, Marco Montorsi, Marco Erreni, Michele Carvello, and Matteo Sacchi
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Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Colorectal cancer ,Internal medicine ,Gastroenterology ,medicine ,business ,medicine.disease - Published
- 2015
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47. Subject Index Vol. 32, Suppl. 1, 2014
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Philippe Marteau, Marte Lie Høivik, Fernando Gomollón, Jonathan M. Rhodes, Clara Thienpont, F. Carbonnel, Satz Mengensatzproduktion, Barry J. Campbell, Marietta Iacucci, Aaron Liew, Antonino Spinelli, Druckerei Stückle, Marco Montorsi, William J. Sandborn, David Laharie, Willem A. Bemelman, Subrata Ghosh, Laurence J. Egan, Shuvra Ray, Gert Van Assche, Gerassimos J. Mantzaris, Øistein Hovde, Gerhard Rogler, Hannah L. Simpson, Theresa T. Pizarro, David Dunkin, Bjørn Moum, E. Joline de Groof, Claudio Fiocchi, Matthieu Allez, Harry Sokol, Jürgen Schölmerich, Silvio Danese, Carlo De Salvo, Axel Dignass, Michele Carvello, Christianne J. Buskens, Bruce E. Sands, Jean-Frederic Colombel, Saurabh Mehandru, and Timothy O'Brien
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medicine.medical_specialty ,Index (economics) ,business.industry ,Gastroenterology ,Physical therapy ,Medicine ,Subject (documents) ,General Medicine ,business - Published
- 2014
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48. Inotuzumab Ozogamicin Murine Analog–Mediated B-Cell Depletion Reduces Anti-islet Allo- and Autoimmune Responses
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Sara Tezza, Paolo Fiorina, Mohamed H. Sayegh, Kyri Dunussi-Joannopoulos, James F. Markmann, Andrea Vergani, M. Carvello, Alessandra Petrelli, Elena Orsenigo, Kang Mi Lee, Melissa Chin, Carlo Staudacher, Antonio Secchi, Michele, Carvello, Alessandra, Petrelli, Andrea, Vergani, Kang Mi, Lee, Sara, Tezza, Melissa, Chin, Elena, Orsenigo, Carlo, Staudacher, Secchi, Antonio, Kyri Dunussi, Joannopoulo, Mohamed H., Sayegh, James F., Markmann, and Paolo, Fiorina
- Subjects
endocrine system ,Endocrinology, Diabetes and Metabolism ,CD3 ,Islets of Langerhans Transplantation ,Priming (immunology) ,Autoimmunity ,Mice, Transgenic ,Mice, SCID ,Nod ,Antibodies, Monoclonal, Humanized ,Islets of Langerhans ,Mice ,Immune system ,Antigen ,Mice, Inbred NOD ,Internal Medicine ,medicine ,Animals ,Inotuzumab Ozogamicin ,Cells, Cultured ,Inotuzumab ozogamicin ,B-Lymphocytes ,Mice, Inbred BALB C ,geography ,geography.geographical_feature_category ,Cell Death ,biology ,Graft Survival ,Antibody-Dependent Cell Cytotoxicity ,Islet ,Mice, Inbred C57BL ,Transplantation ,Immunology ,biology.protein ,Female ,Transplantation Tolerance ,Immunology and Transplantation ,medicine.drug - Abstract
B cells participate in the priming of the allo- and autoimmune responses, and their depletion can thus be advantageous for islet transplantation. Herein, we provide an extensive study of the effect of B-cell depletion in murine models of islet transplantation. Islet transplantation was performed in hyperglycemic B-cell–deficient(μMT) mice, in a purely alloimmune setting (BALB/c into hyperglycemic C57BL/6), in a purely autoimmune setting (NOD.SCID into hyperglycemic NOD), and in a mixed allo-/autoimmune setting (BALB/c into hyperglycemic NOD). Inotuzumab ozogamicin murine analog (anti-CD22 monoclonal antibody conjugated with calicheamicin [anti-CD22/cal]) efficiently depleted B cells in all three models of islet transplantation examined. Islet graft survival was significantly prolonged in B-cell–depleted mice compared with control groups in transplants of islets from BALB/c into C57BL/6 (mean survival time [MST]: 16.5 vs. 12.0 days; P = 0.004), from NOD.SCID into NOD (MST: 23.5 vs. 14.0 days; P = 0.03), and from BALB/c into NOD (MST: 12.0 vs. 5.5 days; P = 0.003). In the BALB/c into B-cell–deficient mice model, islet survival was prolonged as well (MST: μMT = 32.5 vs. WT = 14 days; P = 0.002). Pathology revealed reduced CD3+ cell islet infiltration and confirmed the absence of B cells in treated mice. Mechanistically, effector T cells were reduced in number, concomitant with a peripheral Th2 profile skewing and ex vivo recipient hyporesponsiveness toward donor-derived antigen as well as islet autoantigens. Finally, an anti-CD22/cal and CTLA4-Ig–based combination therapy displayed remarkable prolongation of graft survival in the stringent model of islet transplantation (BALB/c into NOD). Anti-CD22/cal–mediated B-cell depletion promotes the reduction of the anti-islet immune response in various models of islet transplantation.
- Published
- 2012
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