Publications by authors named "Alessandro Zerbi"

113 Publications

Pancreaticoduodenectomy in octogenarians: The importance of "biological age" on clinical outcomes.

Surg Oncol 2021 Nov 24;40:101688. Epub 2021 Nov 24.

Gemelli Pancreatic Center, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy; CRMPG (Advanced Pancreatic Research Center), Largo Agostino Gemelli, 8, 00168, Rome, Italy; Università Cattolica del Sacro Cuore di Roma, Largo Francesco Vito 1, 00168, Rome, Italy.

Introduction: With the prolongation of life expectancy, an increasing number of elderly patients are evaluated for pancreatic surgery. However, the influence of increasing age on outcomes after pancreaticoduodenectomy (PD) is still unclear, especially in octogenarians. Aim of this study is to evaluate the perioperative characteristics and outcomes of octogenarians undergoing PD.

Methods: Data for 812 patients undergoing PD between 2019 and 2020 in 10 referral centers in Italy were reviewed. Patients aged 80 years or older were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients younger than 80 years. Propensity scores were calculated using 7 perioperative variables including gender, ASA score, neoadjuvant treatment (NAT), biliary stent positioning, type of surgical approach (open, laparoscopic, robot-assisted), associated vascular resections, type of lesion. Perioperative characteristics and short-term postoperative outcomes were compared before and after matching.

Results: Overall, 81 (10%) patients had 80 years or more. Before matching, octogenarians had a higher rate of ASA score≥ 3 (n = 35, 43.2% vs. n = 207, 28.3%; p = 0.005) and less frequently underwent NAT (n = 11, 13.6% vs. n = 213, 29.1%; p = 0.003). Matching was successfully performed for 70 octogenarians. After matching, no differences in preoperative and intraoperative characteristics were found. Postoperatively, ICU admission was more frequent in octogenarians (50% vs 30%; p = 0.01). Although in-hospital mortality was higher in octogenarians before matching (7.4% vs 2.9% in the younger cohort; p = 0.03), no difference was noted between the matched cohorts (p = 0.36). Postoperative morbidity was comparable between groups in the whole and selected populations. At the multivariate analysis, chronological age was not recognized as a prognostic factor for cumulative major complications, while ASA ≥3 was the only confirmed influencing feature (OR 2.98; 95%CI: 1.6-6.8; p = 0.009).

Conclusio: In high-volume centers, PD in octogenarians shows similar outcomes than younger patients. Age itself should not be considered an exclusion criterion for PD, but a focused preoperative assessment is essential for adequate patient selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2021.101688DOI Listing
November 2021

Quantitative assessment of the impact of COVID-19 pandemic on pancreatic surgery: an Italian multicenter analysis of 1423 cases from 10 tertiary referral centers.

Updates Surg 2021 Nov 24. Epub 2021 Nov 24.

Department of Surgery, Gemelli Pancreatic Center, Fondazione Policlinico Universitario "Agostino Gemelli", IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.

Few evidences are present on the consequences of coronavirus disease 2019 (COVID-19) pandemic on pancreatic surgery. Aim of this study is to evaluate how COVID-19 influenced the diagnostic and therapeutic pathways of surgical pancreatic diseases. A comparative analysis of surgical volumes and clinical, surgical and perioperative outcomes in ten Italian referral centers was conducted between the first semester 2020 and 2019. One thousand four hundred and twenty-three consecutive patients were included in the analysis: 638 from 2020 and 785 from 2019. Surgical volume in 2020 decreased by 18.7% (p < 0.0001). Benign/precursors diseases (- 43.4%; p < 0.0001) and neuroendocrine tumors (- 33.6%; p = 0.008) were the less treated diseases. No difference was reported in terms of discussed cases at the multidisciplinary tumor board (p = 0.43), mean time between diagnosis and neoadjuvant treatment (p = 0.91), indication to surgery and surgical resection (p = 0.35). Laparoscopic and robot-assisted procedures dropped by 45.4% and 61.9%, respectively, during the lockdown weeks of 2020. No difference was documented for post-operative intensive care unit accesses (p = 0.23) and post-operative mortality (p = 0.06). The surgical volume decrease in 2020 will potentially lead, in the near future, to the diagnosis of a higher rate of advanced stage diseases. However, the reassessment of the Italian Health Service kept guarantying an adequate level of care in tertiary referral centers. Clinicaltrials.gov ID: NCT04380766.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01171-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611384PMC
November 2021

A machine learning risk model based on preoperative computed tomography scan to predict postoperative outcomes after pancreatoduodenectomy.

Updates Surg 2021 Oct 1. Epub 2021 Oct 1.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy.

Clinically relevant postoperative pancreatic fistula (CR-POPF) is a life-threatening complication following pancreaticoduodenectomy (PD). Individualized preoperative risk assessment could improve clinical management and prevent or mitigate adverse outcomes. The aim of this study is to develop a machine learning risk model to predict occurrence of CR-POPF after PD from preoperative computed tomography (CT) scans. A total of 100 preoperative high-quality CT scans of consecutive patients who underwent pancreaticoduodenectomy in our institution between 2011 and 2019 were analyzed. Radiomic and morphological features extracted from CT scans related to pancreatic anatomy and patient characteristics were included as variables. These data were then assessed by a machine learning classifier to assess the risk of developing CR-POPF. Among the 100 patients evaluated, 20 had CR-POPF. The predictive model based on logistic regression demonstrated specificity of 0.824 (0.133) and sensitivity of 0.571 (0.337), with an AUC of 0.807 (0.155), PPV of 0.468 (0.310) and NPV of 0.890 (0.084). The performance of the model minimally decreased utilizing a random forest approach, with specificity of 0.914 (0.106), sensitivity of 0.424 (0.346), AUC of 0.749 (0.209), PPV of 0.502 (0.414) and NPV of 0.869 (0.076). Interestingly, using the same data, the model was also able to predict postoperative overall complications and a postoperative length of stay over the median with AUCs of 0.690 (0.209) and 0.709 (0.160), respectively. These findings suggest that preoperative CT scans evaluated by machine learning may provide a novel set of information to help clinicians choose a tailored therapeutic pathway in patients candidated to pancreatoduodenectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01174-5DOI Listing
October 2021

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading from the International Study Group for Pancreatic Surgery (ISGPS).

Ann Surg 2021 Sep 29. Epub 2021 Sep 29.

Department of Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy Division of Surgery and Perioperative Medicine, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia Mayo Clinic Department of General Surgery, Rochester, NY Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA Department of Surgery, Christchurch Hospital, Christchurch, New Zealand Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Department of Surgery, NYU Grossman School of Medicine, New York, NY Indiana University School of Medicine, Indiana University Health, Indianapolis, IN Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA Digestive Surgery Department, Lyon Civil Hospital, Lyon, France Manchester Royal Infirmary, Manchester, UK Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Surgery, Fondazione Poliambulanza, Brescia, Italy Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians-University, Munich, Germany Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University Munich, Munich, Germany Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Asklepios Harzklinik, Goslar, Germany Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland Department of Surgery, AGIA OLGA Hospital, Athens, Greece School of Medicine and Surgery, Milano - Bicocca University, and Department of Surgery, San Gerardo Hospital, Monza, Italy Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO Department of Surgery, Humanitas University and Research Hospital IRCCS, Milan, Italy The Petz Aladar Hospital, Gyor, Hungary Department of HPB Surgery and Liver Transplant, Royal Free Hospital NHS Foundation Trust, London, UK Department of Surgery, Miguel Servet University Hospital, Paseo Isabel la Catolica, Zaragoza, Spain University of Graz Hospital, Surgical Research Unit, Graz, Austria Department of Surgery, Clinical Sciences Lund, Lund University, Lund, Sweden Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India.

Objective: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison.

Background: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking.

Methods: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021.

Results: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative hyperamylasemia greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications.

Discussions: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005226DOI Listing
September 2021

Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): study protocol for a randomized controlled trial.

Trials 2021 Sep 9;22(1):608. Epub 2021 Sep 9.

Department of Surgery, Emory University Hospital, Atlanta, USA.

Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP.

Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively.

Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.

Trial Registration: ISRCTN registry ISRCTN44897265 . Prospectively registered on 16 April 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05506-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427847PMC
September 2021

Pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous tumor: Different prognostic factors for different overall survival.

Dig Liver Dis 2021 Jul 1. Epub 2021 Jul 1.

Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy; Humanitas University Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy.

Background: It is unclear whether invasive intraductal papillary mucinous neoplasm (IPMN) has different clinical and prognostic characteristics, beyond histological factors, when compared to pancreatic ductal adenocarcinoma (PDAC).

Aims: compare prognostic features of resected PDAC and invasive IPMN METHODS: A retrospective study of patients resected for PDAC or invasive IPMN realized at Humanitas Cancer Center's Pancreatic Surgery Unit, Milan, Italy, between 2010 and 2016. Data recorded included patient demographics, onset symptoms, preoperative health status, tumor features, histology and surgical characteristics. Overall survival was estimated using Kaplan-Meier and prognostic factors for survival were assessed by multivariate Cox regression.

Results: A total of 332 patients were included (PDAC, n = 289; invasive IPMN, n = 43). Patients with invasive IPMN had better overall survival than PDAC patients (median: 76.6 versus 25.6 months; 5-year OS rate: 65.4% vs. 14.2%; p < 0.001). PDAC histology was associated with a significantly higher risk of death than IPMN (hazard ratio 1.815, 95% CI: 1.02, 3.24; p = 0.044). Survival was also worse with PDAC in early-stage disease (IA-IB-IIA, N0). In multivariate analysis, independent predictors of worse survival included perineural invasion, preoperative ASA physical status ≥3 and pain at diagnosis.

Conclusions: Patients with IPMN had a better prognosis than PDAC patients, regardless of disease stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2021.06.006DOI Listing
July 2021

Borderline resectable pancreatic cancer: Certainties and controversies.

World J Gastrointest Surg 2021 Jun;13(6):516-528

Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy.

Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4240/wjgs.v13.i6.516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223708PMC
June 2021

Evidence Map of Pancreatic Surgery-A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS).

Surgery 2021 11 27;170(5):1517-1524. Epub 2021 Jun 27.

Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Germany.

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery.

Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates.

Results: Out of 30,860 articles reviewed, 328 randomized controlled trials on 35,600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%-2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%-1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%-61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%-80%) for distal pancreatectomy.

Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2021.04.023DOI Listing
November 2021

Short-Term Outcomes After Spleen-Preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-Volume Centers.

Ann Surg 2021 Jun 2. Epub 2021 Jun 2.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands Department of General Surgery, Instituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy Department of Surgery, Morriston Hospital, Swansea, United Kingdom Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Sweden Division of General and Transplant Surgery, University of Pisa, Pisa, Italy Department of Surgery, Pederzoli Hospital, Peschiera, Italy Department of Surgery, S. Orsola-Malpighi Hospital, Bologna, Italy Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy Department of Surgery, Hopital Saint Eloi, Montpellier, France Department of Surgery, Niguarda Ca' Granda Hospital, Milan, Italy Department of Surgery, Hospital of Beaujon, Clichy, France Department of Surgery, Royal Free Hospital NHS Foundation Trust, London, United Kingdom Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium Department of Hepatobiliary and Pancreatic Surgery, Addenbrooke's Hospital, Cambridge, UK Department of Surgery, University Hospital Schleswig Holstein, Campus Lübeck, Lübeck, Germany Emergency and General Surgery Department, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy and General Surgery Department, Policlinico Abano Terme, Italy Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Utrecht University, Utrecht, the Netherlands Department of Visceral and Digestive Surgery, Nouvel Hôpital Civil, University hospital of Strasbourg Department of Surgery, University hospital Pavia, Pavia, Italy The Intervention Center, Department of HPB Surgery, Department of Research & Development, Division of Emergencies and Critical Care Oslo University Hospital and Institute for Clinical Medicine, University of Oslo, Norway Department of Research & Development, Division of Emergencies and Critical Care, Oslo University Hospital Department of Surgery, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom Department of Surgery, the Freeman Hospital Newcastle Upon Tyne, Newcastle, United Kingdom Pancreatic Surgery, Humanitas IRCCS, Rozzano and Humanitas University, Department of Biomedical Sciences, Milan, Italy Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom.

Objective: To compare short-term clinical outcomes after Kimura and Warshaw minimally invasive distal pancreatectomy (MIDP).

Background: Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce.

Methods: Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in eight European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ('rescue') Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP.

Results: Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs. 1.6%, p = 0.127) and major complications (11.5% vs 14.4%, p = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs. 1.2%, p = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, p = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 min, p = 0.033) and less blood loss (100 vs 150 ml, p < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, p < 0.001).

Conclusion: Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004963DOI Listing
June 2021

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial.

Cancers (Basel) 2021 Apr 26;13(9). Epub 2021 Apr 26.

Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection.

Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated.

Results: One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively ( > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP.

Conclusions: The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123600PMC
April 2021

Total pancreatectomy as alternative to pancreatico-jejunal anastomosis in patients with high fistula risk score: the choice of the fearful or of the wise?

Langenbecks Arch Surg 2021 May 30;406(3):713-719. Epub 2021 Mar 30.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, 20090, Pieve Emanuele, MI, Italy.

Purpose: Patients with fistula risk score (FRS) ≥7 are at the highest risk of developing clinically relevant post-operative pancreatic fistula (CR-POPF). There is no agreement on the management of this subpopulation. The primary outcome of the study was the definition of the role of intraoperative completion pancreatectomy (ICP) in patients at high risk for CR-POPF, as an alternative to high-risk pancreaticoduodenectomy (PD).

Methods: This is an observational study set in a single tertiary referral center. Patients scheduled for PD in our center between 2010 and 2019 with FRS ≥7 were included in the study. Data were prospectively collected.

Results: A total of 738 patients were scheduled for between 2010 and 2019, and 62 had FRS ≥7. Thirty-five patients were managed with PD and pancreatico-jejunal anastomosis (group A), and 27 with ICP (group B). Overall complication rate was significantly higher in group A than group B (95 versus 59%; p=0.005) and there was a not significantly higher rate of major complications (Clavien-Dindo ≥3) (43 versus 26%; p=0.192). In group A, 49% of patients had a CR-POPF. Median post-operative length of stay was 15 days in group A and 12 in group B (p=0.043). Readmission was observed only in group A (26%). In multivariate analysis, PD was an independent predictive factor of major post-operative morbidity (RR 9.27; CI 1.74-49.31). No patients in either group suffered major adverse events related to endocrine and exocrine insufficiency.

Conclusion: In high-FRS patients, ICP has good short-term outcomes relative to PD without major long-term events related to endocrine and exocrine insufficiency. ICP could be considered as a feasible alternative in selected cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00423-021-02157-1DOI Listing
May 2021

[Correlations between pancreatic carcinoma and previous neoplasms.]

Recenti Prog Med 2021 Jan;112(1):81-88

UO Chirurgia Pancreatica, Humanitas Clinical and Research Center - IRCCS, Rozzano (Milano) - Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (Milano).

Introduction: Into blood relatives of patients affected by breast cancer, the prevalence of pancreatic ductal adenocarcinoma (PDAC) seems to be elevated. BRCA1/2 mutations as other VUS (variants of uncertain significance) could be responsible.

Methods: We retrospectively revised dataset of Pancreatic Surgery Unit of Humanitas Clinical and Research Center - IRCCS and identified patients who underwent resection for PDAC between 2010 and 2018. We evaluated neoplastic family history and remote pathological history, particularly for breast and prostate tumors. The characteristics of family history were described. Overall survival (OS) and progression free survival (PFS) were calculated for different identified groups.

Results: 483 PDAC have been analyzed; 57% had a family history positive for neoplasia; 25% at least showed a blood relative affected by one of these type of cancers: PDAC, breast and prostate, of which 88% was a first degree relative (FDR). One hundred and six patients (22%) had a previous neoplasia, of which 8% a breast cancer and 4% a prostate one. Into this group of patients, 54% had a family history positive for neoplasia and 23% consisted of either a pancreatic neoplasm, or breast tumor or prostate cancer; 71% was a FDR. With a median follow-up of 54.9 months (range 0.066-120), the median survival was 22,8 months. Both OS than PFS weren't statistically significant, considering family history and remote pathological history.

Conclusions: There appears to be a high prevalence of breast and prostate cancer in family members and patients with PDAC. PDAC patients have the prognosis of the pancreatic cancer, not influenced by a previous treated neoplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1701/3525.35128DOI Listing
January 2021

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study.

Front Med (Lausanne) 2020 23;7:598438. Epub 2020 Dec 23.

National NET Centre and ENETS Centre of Excellence, St Vincent's University Hospital, Dublin, Ireland.

The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017-2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at Gallium DOTATOC-PET scan. The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.598438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785972PMC
December 2020

Pancreatic serous cystoadenoma (CSA) showing increased tracer uptake at 68-GaDOTA-peptide Positron Emission Tomography (68Ga-DOTA-peptide PET-CT): a case report.

BMC Surg 2020 Dec 14;20(1):331. Epub 2020 Dec 14.

Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Via Alessandro Manzoni, 56, 20089, Rozzano, Milan, Italy.

Background: Serous cysto-adenoma (SCA) is a rare benign neoplasm of the pancreas. SCA can mimic other pancreatic lesions, such as neuroendocrine tumours. 68Gallium-DOTA-peptide Positron Emission Tomography (PET) is able to image in vivo the over-expression of the somatostatin receptors, playing an important role for the identification of neuroendocrine neoplasms.

Case Presentation: We reported a case of 63-year-old man, with a solid lesion of 7 cm of diameter of the body-tail of the pancreas. Two fine-needle-aspirations (FNA) were inconclusive. A 68Ga-DOTA-peptide PET-CT revealed a pathological uptake of the pancreatic lesion. The diagnosis of a pancreatic neuroendocrine neoplasm was established and a laparoscopic distal splenopancreatectomy and cholecystectomy was performed. Final histopathological report revealed the presence of a micro-cystic SCA.

Conclusions: The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12893-020-01004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737276PMC
December 2020

Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma.

J Vis Exp 2020 11 5(165). Epub 2020 Nov 5.

Department of Immunology and Inflammation, Humanitas Clinical and Research Center-IRCCS;

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death, and soon to become the second. There is an urgent need of variables associated to specific pancreatic pathologies to help preoperative differential diagnosis and patient profiling. Pancreatic juice is a relatively unexplored body fluid, which, due to its close proximity to the tumor site, reflects changes in the surrounding tissue. Here we describe in detail the intraoperative collection procedure. Unfortunately, translating pancreatic juice collection to murine models of PDAC, to perform mechanistic studies, is technically very challenging. Tumor interstitial fluid (TIF) is the extracellular fluid, outside blood and plasma, which bathes tumor and stromal cells. Similarly to pancreatic juice, for its property to collect and concentrate molecules that are found diluted in plasma, TIF can be exploited as an indicator of microenvironmental alterations and as a valuable source of disease-associated biomarkers. Since TIF is not readily accessible, various techniques have been proposed for its isolation. We describe here two simple and technically undemanding methods for its isolation: tissue centrifugation and tissue elution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/61687DOI Listing
November 2020

Clinical Outcomes after Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

Ann Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Objective: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality.

Background: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice.

Methods: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cut-off values for annual volume of pancreatoduodenectomies (<60 vs. ≥60). Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression.

Results: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared < 60 (4% vs. 10%, p = 0.046). In multivariable analysis, annual volume < 60 pancreatoduodenectomies (OR 3.78, 95%CI 1.18-12.16, p = 0.026), age (OR 1.07, 95%CI 1.01-1.14, p = 0.046), and estimated blood loss ≥2L (OR 11.89, 95%CI 2.64-53.61, p = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95%CI 1.56-5.26, p = 0.001) and estimated blood loss ≥2L (OR 3.52, 95%CI 1.25-9.90, p = 0.017) were associated with major complications.

Conclusion: This pan-European prospective snapshot study found a 5% in-hospital after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004551DOI Listing
November 2020

Endoscopic ultrasound guided gastroenterostomy for efferent jeunal loop obstruction in a patient with previous pancreaticoduodenectomy and ascites.

Endosc Int Open 2020 Oct 22;8(10):E1435-E1436. Epub 2020 Sep 22.

Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano (Milano), Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1221-5183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508657PMC
October 2020

Pancreatic Cancer Cells Require the Transcription Factor MYRF to Maintain ER Homeostasis.

Dev Cell 2020 11 29;55(4):398-412.e7. Epub 2020 Sep 29.

Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy; Humanitas University, Pieve Emanuele, Milano, Italy. Electronic address:

Many tumors of endodermal origin are composed of highly secretory cancer cells that must adapt endoplasmic reticulum (ER) activity to enable proper folding of secreted proteins and prevent ER stress. We found that pancreatic ductal adenocarcinomas (PDACs) overexpress the myelin regulatory factor (MYRF), an ER membrane-associated transcription factor (TF) released by self-cleavage. MYRF was expressed in the well-differentiated secretory cancer cells, but not in the poorly differentiated quasi-mesenchymal cells that coexist in the same tumor. MYRF expression was controlled by the epithelial identity TF HNF1B, and it acted to fine-tune the expression of genes encoding highly glycosylated, cysteine-rich secretory proteins, thus preventing ER overload. MYRF-deficient PDAC cells showed signs of ER stress, impaired proliferation, and an inability to form spheroids in vitro, while in vivo they generated highly secretory but poorly proliferating and hypocellular tumors. These data indicate a role of MYRF in the control of ER homeostasis in highly secretory PDAC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2020.09.011DOI Listing
November 2020

Italian registry of families at risk of pancreatic cancer: AISP Familial Pancreatic Cancer Study Group.

Dig Liver Dis 2020 10 17;52(10):1126-1130. Epub 2020 Aug 17.

Pancreatic Surgery Unit, Vita-Salute University, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Università. Vita-Salute, Milan, Italy.

Pancreatic cancer is one of the main causes of cancer-related death worldwide, with a survival rate around 9%. In Italy 13,500 new cases of pancreatic cancer occurred in 2019. It is estimated that at least 5% have a hereditary background. Surveillance is advisable for healthy individuals with specific genetic syndromes with or without family history of pancreatic cancer or members of families with multiple cases of pancreatic cancer, irrespective of genetic syndromes. In 2010 the Italian Association for the Study of the Pancreas (AISP) defined criteria to include individuals in such surveillance programs with the first-round results published in 2019. In order to include other categories at high-risk and increase the diagnostic yield of surveillance, these criteria have recently been modified. The present position paper presents the updated criteria of the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) with their diagnostic yield calculation. Also, AISP priority projects concerning: (a) increasing awareness of citizens and primary care physicians through a dedicated App; (b) increasing access to germline testing to personalize surveillance; (c) measuring psychological impact of surveillance; (d) investigating the role of risk-modifiers and (e) evaluating the cost-effectiveness and ability to save lives of the program are briefly presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.07.027DOI Listing
October 2020

Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study.

HPB (Oxford) 2021 Mar 8;23(3):379-386. Epub 2020 Aug 8.

Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.

Background: Resection margin status and lymph node (LN) involvement are known prognostic factors for patients who undergo pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare overall survival (OS) and disease-free survival (DFS) by resection margin status in patients with PDAC and LN involvement.

Methods: A retrospective international multicentric study was performed including four Western centers. Multivariable Cox analysis was performed to identify prognostic factors of OS and DFS. Median OS and DFS were calculated using Kaplan-Meier curves and compared using log-rank tests.

Results: A cohort of 814 PDAC patients with pancreatoduodenectomy were analyzed. A total of 651 patients had LN involvement (80%). On multivariable analysis R1 resection was not an independent factor of worse OS and DFS in patients with LN involvement (HR 1.1, p = 0.565; HR 1.2, p = 0.174). Only tumor size, grade, and adjuvant chemotherapy were associated with OS and DFS. Median OS and DFS were similar between patients with R0 and R1 resections (23 vs. 20 months, p = 0.196; 15 vs. 14 months, p = 0.080).

Conclusion: Resection status was not identified as predictor of OS or DFS in PDAC patients with LN involvement. Extensive surgery to achieve R0 resection in such patients might not influence the disease course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2020.07.008DOI Listing
March 2021

Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment.

Cancers (Basel) 2020 Aug 2;12(8). Epub 2020 Aug 2.

Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy.

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.

Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination.

Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% ± 13%, < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression.

Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12082143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464161PMC
August 2020

Enhanced Recovery After Pancreatic Surgery Does One Size Really Fit All? A Clinical Score to Predict the Failure of an Enhanced Recovery Protocol After Pancreaticoduodenectomy.

World J Surg 2020 Nov 30;44(11):3600-3606. Epub 2020 Jul 30.

Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, via Manzoni 56, 20089, Rozzano, Milan, Italy.

Background: The inability to comply with enhanced recovery protocols (ERp) after pancreaticoduodenectomy (PD) is a real but understated issue. Our goal is to report our experience and a potential tool to predict ERp failure in order to better characterize this problem.

Methods: From January 1, 2014, to January 31, 2016, 205 consecutive patients underwent PD in our center and were managed according to an ERp. Failure to comply with postoperative protocol items was defined as any of: no active ambulation on postoperative day 1 (POD1); less than 4 h out of bed on POD2; removal of nasogastric tube and bladder catheter after POD1 and POD3, respectively; reintroduction of oral feeding after POD4; and continuation of intravenous infusions after POD4. Data were collected in a prospective database.

Results: Taking in consideration the number of failed items and the length of stay, we defined failure of the ERp as no compliance to two or more items. A total of 116 patients (56.6%) met this definition of failure. We created a predictive model consisting of age, BMI, operative time, and pancreatic stump consistency. These variables were independent predictors of failure (OR 1.03 [1.001-1.06] p = 0.01; OR 1.11 [1.01-1.22] p = 0.03; OR 1.004 [1.001-1.009] p = 0.02 and OR 2.89 [1.48-5.67] p = 0.002, respectively). Patient final score predicted the failure of the ERp with an area under the ROC curve of 0.747.

Conclusions: It seems to be possible to predict ERp failure after PD. Patients at high risk of failure may benefit more from a specific ERp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05693-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527369PMC
November 2020

A Snapshot of Elective Oncological Surgery in Italy During COVID-19 Emergency: Pearls, Pitfalls, and Perspectives.

Ann Surg 2020 08;272(2):e112-e117

Division of General & Emergency Surgery, Department of Surgery, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy.

Objective: To analyze the impact of COVID-19 emergency on elective oncological surgical activity in Italy.

Summary Of Background Data: COVID-19 emergency shocked national health systems, subtracting resources from treatment of other diseases. Its impact on surgical oncology is still to elucidate.

Methods: A 56-question survey regarding the oncological surgical activity in Italy during the COVID-19 emergency was sent to referral centers for hepato-bilio-pancreatic, colorectal, esophago-gastric, and sarcoma/soft-tissue tumors. The survey portrays the situation 5 weeks after the first case of secondary transmission in Italy.

Results: In total, 54 surgical Units in 36 Hospitals completed the survey (95%). After COVID-19 emergency, 70% of Units had reduction of hospital beds (median -50%) and 76% of surgical activity (median -50%). The number of surgical procedures decreased: 3.8 (interquartile range 2.7-5.4) per week before the emergency versus 2.6 (22-4.4) after (P = 0.036). In Lombardy, the most involved district, the number decreased from 3.9 to 2 procedures per week. The time interval between multidisciplinary discussion and surgery more than doubled: 7 (6-10) versus 3 (3-4) weeks (P < 0.001). Two-third (n = 34) of departments had repeated multidisciplinary discussion of patients. The commonest criteria to prioritize surgery were tumor biology (80%), time interval from neoadjuvant therapy (61%), risk of becoming unresectable (57%), and tumor-related symptoms (52%). Oncological hub-and-spoke program was planned in 29 departments, but was active only in 10 (19%).

Conclusions: This survey showed how surgical oncology suffered remarkable reduction of the activity resulting in doubled waiting-list. The oncological hub-and-spoke program did not work adequately. The reassessment of healthcare systems to better protect the oncological path seems a priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373476PMC
August 2020

The Applicability of a Checklist for the Diagnosis and Treatment of Exocrine Pancreatic Insufficiency: Results of the Italian Exocrine Pancreatic Insufficiency Registry.

Pancreas 2020 07;49(6):793-798

Pancreatic Surgery, Humanitas Hospital, Milan, Italy.

Objective: To evaluate a rapid checklist capable of identifying exocrine pancreatic insufficiency in outpatients.

Methods: Prospective observational study of a multicenter cohort.

Results: One hundred and two patients were enrolled; 61.8% of the patients had medically-treated benign or malignant pancreatic disease, and 38.2% had a pancreatic resection. Visual examination of the feces was evaluated in 84 patients and it was related to steatorrhea in 51 patients (50.0%). Receiver operating characteristic curves were evaluated for each symptom or clinical sign and four of them (ie, increase in daily bowel movements, number of bowel movements, fatty stools, >10% weight loss) had a satisfactory area under the curve. At multivariate analysis, fatty stools and >10% weight loss entered into this analysis having an area under the curve of 0.916 (95% confidence interval, 0.851-0.981). At 1 month and at one year of follow-up, the pancreatic enzyme replacement therapy administered showed that pancreatic extracts were able to significantly improve the increase in daily bowel movements, the number of bowel movements, fatty and bulky stools and >10% weight loss.

Conclusion: Both fatty stools and >10% weight loss were able to clinically evaluate steatorrhea, and their improvement was sufficient to evaluate substitution therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001575DOI Listing
July 2020

The Italian National Registry for minimally invasive pancreatic surgery: an initiative of the Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS).

Updates Surg 2020 Jun 29;72(2):379-385. Epub 2020 May 29.

Università di Pisa, Pisa, Italy.

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6-10 cases in 38.9% of the centers, 11-20 cases in 16.7%, 21-30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-020-00808-4DOI Listing
June 2020

Emergency endovascular treatments for delayed hemorrhage after pancreaticobiliary surgery: indications, outcomes, and follow-up of a retrospective cohort.

Abdom Radiol (NY) 2020 08;45(8):2593-2602

Department of Diagnostic and Interventional Radiology, Humanitas Research Hospital, Via A. Manzoni 56, 20089, Rozzano, Milano, Italy.

Purpose: To evaluate the outcomes of emergency endovascular treatments for delayed bleeding after pancreaticobiliary surgery.

Methods: We retrospectively evaluated 21 patients (M:F = 13:8, median age = 64 years) undergoing 23 endovascular treatments, performed from 2010 to 2017 in a single center. Data collected were patient characteristics; surgery; pathology; incidence of postoperative pancreatic fistulas (POPF); bleeding signs on CT and angiography; damaged artery; endovascular tools used; technical and clinical success; intervals between surgery, endovascular treatment, and discharge; survival rates.

Results: Sixteen patients had pancreatoduodenectomy, three hepaticojejunostomy, two distal pancreatectomy. Indications for surgery were mainly biliary (33%), pancreatic (19%), or duodenal (10%) malignancies. Seventeen patients had "grade C" POPF, three suffered a biliary leak, one had no POPF. Active bleeding was present in 17/23 CTs and in 22/23 angiographies, mostly from hepatic (43%), gastroduodenal (22%), and splenic (13%) arteries. The endovascular treatments were performed with coils (26%), glue (22%), stent-graft (22%), and their combinations (30%). Sixteen patients had a single endovascular treatment, one underwent a second embolization, three had subsequent surgery, one had repeat embolization followed by surgery. Relaparotomy rate was 19%. Median hospital stay was 37 days (range 12-75); median intervals among pancreaticobiliary surgery, endovascular treatment, and discharge were 21 (2-36) and 12 (8-47) days, respectively. We observed 4/21 intrahospital deaths (median: 31 days from endovascular treatment, 4-53); 1-year survival rate of discharged patients was 71%.

Conclusions: Endovascular treatment using embolization and/or stent-graft placement is a useful first-line intervention to halt postoperative hemorrhage after pancreaticobiliary surgery and decreases the need for urgent relaparotomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-020-02480-zDOI Listing
August 2020

Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1 Cells.

Cancer Immunol Res 2020 04 4;8(4):493-505. Epub 2020 Feb 4.

Department of Immunology and Inflammation, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1 T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1 CD8 tumor-infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase () gene displayed a decrease in PD-1 cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2326-6066.CIR-19-0403DOI Listing
April 2020

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study.

Pancreatology 2020 Apr 21;20(3):433-441. Epub 2020 Jan 21.

Department of Surgery, University Medical Center Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23562, Luebeck, Germany.

Background/objective: The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.

Methods: Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.

Results: 214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.

Conclusion: Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2020.01.009DOI Listing
April 2020

Preoperative adiposity at bioimpedance vector analysis improves the ability of Fistula Risk Score (FRS) in predicting pancreatic fistula after pancreatoduodenectomy.

Pancreatology 2020 Apr 16;20(3):545-550. Epub 2020 Jan 16.

School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy.

Background: Anthropometric parameters have been associated with increased risk of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Nonetheless, conventional metrics to predict POPF do not include the assessment of body composition. We aimed to validate the most used Fistula Risk Score (FRS), and to assess whether the appraisal of adipose compartment at bioimpedance vector analysis (BIVA) improves the accuracy of FRS in CR-POPF prediction.

Method: PD patients from 3 Italian academic institutions were prospectively included over a 2-year period. Patients with ASA score ≥3, heart failure, chronic kidney disease, or compartmentalized fluid collections were excluded. BIVA was performed on the day prior to surgery. CR-POPF occurrence and severity were classified per the ISGPS classification.

Results: Out of 148 PDs, 84 patients (56.8%) had pancreatic cancer, and 29 (19.6%) experienced CR-POPF. FRS elements, namely soft pancreatic texture (p = 0.009), small pancreatic duct diameter (p = 0.029), but not blood loss (p = 0.450), as well as high BMI (p = 0.004) were associated with CR-POPF. Also, the preoperative fat mass (FM) amount measured at BIVA was significantly higher in patients who developed CR-POPF, compared to those who did not (median FM = 19.4 kg/m2 vs. 14.4 kg/m2, respectively; p = 0.005). The predictive ability of a multivariate model adding FM to the FRS, assessed at the receiver operating characteristics curve showed a higher accuracy than the FRS alone (AUC = 0.774 and AUC = 0.738, respectively).

Conclusions: Assessment of preoperative FM at BIVA can improve the accuracy of FRS in predicting CR-POPF following pancreatoduodenectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2020.01.008DOI Listing
April 2020
-->