Publications by authors named "Massimo Falconi"

419 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

The impact of preoperative anemia on pancreatic resection outcomes.

HPB (Oxford) 2021 Oct 6. Epub 2021 Oct 6.

Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Background: Preoperative anemia is a risk factor for blood transfusions and delayed postoperative recovery, but few data are available for pancreatic surgery. Aim of the study was to analyze the impact of preoperative anemia on outcomes after pancreatic resection.

Methods: Retrospective review of 1107 patients resected at San Raffaele Hospital (2015-2018). Preoperative anemia was defined as hemoglobin lower than 130 g/L for men and 120 g/L for women. Primary outcome was 90-day comprehensive complication index (CCI). Analysis was stratified according to type of surgery; proximal resections (pancreaticoduodenectomy and total pancreatectomy) versus distal pancreatectomy.

Results: In 776 proximal resection patients, preoperative anemia was associated with increased CCI (24 ± 25 vs. 19 ± 23, p = 0.018) and perioperative allogenic blood transfusions (n = 124, 46% vs. n = 129, 26%; p < 0.001). Multivariate analysis showed that anemia was associated with a 7% (95%CI 0.02-0.57 p = 0.047) increase in CCI, and was an independent factor associated with perioperative blood transfusion (OR 2.762, 95%CI 1.72-4.49, p < 0.001). In 331 distal pancreatectomies, anemia was not associated to increased morbidity but only to an increased risk of perioperative blood transfusion.

Conclusion: Preoperative anemia is an independent risk factor for increased complication severity and blood transfusion in patients undergoing major pancreatic resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2021.09.022DOI Listing
October 2021

Evaluation of factors predicting loss of benefit provided by laparoscopic distal pancreatectomy compared to open approach.

Updates Surg 2021 Oct 23. Epub 2021 Oct 23.

Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy.

Several studies showed safety and feasibility of laparoscopic distal pancreatectomy (LDP) as compared to open distal pancreatectomy (ODP). Patients who underwent LDP or ODP (2015-2019) were included. A 1:1 propensity score matching (PSM) was used to reduce the effect of treatment selection bias. Aim of this study was to identify those factors influencing the loss of benefit (defined as a significantly better outcome compared to ODP) after LDP. Overall, 387 patients underwent DP (n = 250 LDP, n = 137 ODP). After PSM, 274 patients (n = 137 LDP, n = 137 ODP) were selected. LDP was associated with reduced intraoperative blood loss (median: 200 mL vs. 250 mL, p < 0.001), decreased wound infection rate (1% vs. 9%, p = 0.044) and shorter time to functional recovery (TFR) (median: 4 days vs. 5 days, p = 0.002). Consequently, TFR > 5 days and blood loss > 250 mL were defined as loss of benefit after LDP. In the LDP group, age > 70 years [Odds Ratio (OR) 2.744, p = 0.022] and duration of surgery > 208 min (OR 2.957, p = 0.019) were predictors of TFR > 5 days and intraoperative blood loss > 250 mL, respectively. No differences in terms of TFR were found between ODP and LDP groups in patients > 70 years (p = 0.102). Intraoperative blood loss was significantly higher in the ODP group, also when the analysis was limited to surgical procedures with operative time > 208 min (p = 0.003). In conclusion, LDP seems comparable to ODP in terms of TFR in patients aged > 70 years. This finding could be helpful in the choice of the best surgical approach in elderly patients undergoing potentially challenging DPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01194-1DOI Listing
October 2021

Diagnostic accuracy of EUS-FNA in the evaluation of pancreatic neuroendocrine neoplasms grading: Possible clinical impact of misclassification.

Endosc Ultrasound 2021 Sep-Oct;10(5):372-380

Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy.

Background And Objectives: Prognosis of pancreatic neuroendocrine neoplasms (PanNENs) mostly depend on tumor stage and grade, determined by Ki-67 labeling index. EUS-FNA is considered the gold-standard technique to obtain it. The aims of our study were to establish diagnostic accuracy of preoperative EUS-FNA Ki-67 evaluation considering final pathological assessment on surgical specimen as gold standard and to investigate the possible impact on prognosis of misclassification.

Methods: This is a retrospective study from a prospectively collected database. EUS-FNA grading (eG) and surgical one (sG) measured according to Ki-67 proliferative index values, according to 2017 WHO classification, were compared. eG-sG correlation was evaluated by Spearman index. Logistic regression investigated factors associated with misclassification. Prognostic difference in terms of progression-free survival was evaluated by Kaplan Meier method.

Results: One hundred and twelve PanNENs patients enrolled. In 13.4% of patients (15/112) EUS-FNA "undergraded" patients (eG1 vs. sG2), while in 12.5% (n = 14) it "overgraded" PanNENs (eG2 to sG1). No misclassifications in G3 patients. In patients with tumors <20 mm (n = 44), 2 (4.5%) eG1 and 10 (22.7%) eG2 were finally classified respectively as G2 and G1 at surgical histology. No factors, as i.e. the lesions' size or their morphological aspect, were associated with misclassification. In overgraded PanNENs, no progression occurred, while in patients correctly classified/undergraded the progression rate was 14.3%.

Conclusions: This is the largest cohort of surgical PanNENs with preoperative EUS-FNA grading evaluation. Despite an acceptable eG-sG correlation, about 25% of patients are misclassified. Clinical impact of misclassification should be carefully considered especially in small tumors undergoing observation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/EUS-D-20-00261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544016PMC
October 2021

EZH2 Inhibition as New Epigenetic Treatment Option for Pancreatic Neuroendocrine Neoplasms (PanNENs).

Cancers (Basel) 2021 Oct 7;13(19). Epub 2021 Oct 7.

Institute of Pathology, University of Bern, 3008 Bern, Switzerland.

Pancreatic neuroendocrine neoplasms are epigenetically driven tumors, but therapies against underlying epigenetic drivers are currently not available in the clinical practice. We aimed to investigate EZH2 (Enhancer of Zest homolog) expression in PanNEN and the impact of EZH2 inhibition in three different PanNEN preclinical models. EZH2 expression in PanNEN patient samples ( = 172) was assessed by immunohistochemistry and correlated with clinico-pathological data. Viability of PanNEN cell lines treated with EZH2 inhibitor (GSK126) was determined in vitro. Lentiviral transduction of shRNA targeting EZH2 was performed in QGP1 cells, and cell proliferation was measured. Rip1TAG2 mice underwent GSK126 treatment for three weeks starting from week 10 of age. Primary cells isolated from PanNEN patients ( = 6) were cultivated in 3D as islet-like tumoroids and monitored for 10 consecutive days upon GSK126 treatment. Viability was measured continuously for the whole duration of the treatment. We found that high EZH2 expression correlated with higher tumor grade ( < 0.001), presence of distant metastases ( < 0.001), and shorter disease-free survival ( < 0.001) in PanNEN patients. Inhibition of EZH2 in vitro in PanNEN cell lines and in patient-derived islet-like tumoroids reduced cell viability and impaired cell proliferation, while inhibition of EZH2 in vivo in Rip1TAG2 mice reduced tumor burden. Our results show that EZH2 is highly expressed in high-grade PanNENs, and during disease progression it may contribute to aberrations in the epigenetic cellular landscape. Targeting EZH2 may represent a valuable epigenetic treatment option for patients with PanNEN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13195014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508156PMC
October 2021

Prediction of Early Distant Recurrence in Upfront Resectable Pancreatic Adenocarcinoma: A Multidisciplinary, Machine Learning-Based Approach.

Cancers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

Department of Radiology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Despite careful selection, the recurrence rate after upfront surgery for pancreatic adenocarcinoma can be very high. We aimed to construct and validate a model for the prediction of early distant recurrence (<12 months from index surgery) after upfront pancreaticoduodenectomy. After exclusions, 147 patients were retrospectively enrolled. Preoperative clinical and radiological (CT-based) data were systematically evaluated; moreover, 182 radiomics features (RFs) were extracted. Most significant RFs were selected using minimum redundancy, robustness against delineation uncertainty and an original machine learning bootstrap-based method. Patients were split into training ( = 94) and validation cohort ( = 53). Multivariable regression analysis was first applied on the training cohort; the resulting prognostic index was then tested in the validation cohort. Clinical (serum level of CA19.9), radiological (necrosis), and radiomic (SurfAreaToVolumeRatio) features were significantly associated with the early resurge of distant recurrence. The model combining these three variables performed well in the training cohort ( = 0.0015, HR = 3.58, 95%CI = 1.98-6.71) and was then confirmed in the validation cohort ( = 0.0178, HR = 5.06, 95%CI = 1.75-14.58). The comparison of survival curves between low and high-risk patients showed a -value <0.0001. Our model may help to better define resectability status, thus providing an actual aid for pancreatic adenocarcinoma patients' management (upfront surgery vs. neoadjuvant chemotherapy). Independent validations are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13194938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508250PMC
September 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

Adjuvant Radiotherapy in Patients With Pancreatic Adenocarcinoma. Is It Still Appealing in Clinical Trials? A Meta-analysis and Review of the Literature.

Anticancer Res 2021 Oct;41(10):4697-4704

Unit of Radiation Oncology, Pisa University Hospital, Pisa, Italy.

Aim: Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies.

Materials And Methods: Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird.

Results: Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting.

Conclusion: We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15283DOI Listing
October 2021

Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial.

Cancers (Basel) 2021 Sep 8;13(18). Epub 2021 Sep 8.

Pancreas Translational & Clinical Research Center, Pancreato-Biliary Endoscopy & Endosonography Division, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, 20132 Milan, Italy.

Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms ( = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients ( = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients ( = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13184512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464946PMC
September 2021

Diameter of surgical versus endoscopic ultrasound-guided gastrojejunostomy: that much wider after all is said and done?

Endoscopy 2021 Sep 17. Epub 2021 Sep 17.

Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1562-1274DOI 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

ASO Visual Abstract: Long-Term Survivors After Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival.

Ann Surg Oncol 2021 Dec 30;28(Suppl 3):655-656. Epub 2021 Aug 30.

Division of Pancreatic Surgery, Department of Surgery, Pancreas Translational and Clinical Research Center, Università Vita- Salute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10573-2DOI Listing
December 2021

Correction to: Total pancreatectomy sequelae and quality of life: results of islet autotransplantation as a possible mitigation strategy.

Updates Surg 2021 Dec;73(6):2403

Chirurgia del Pancreas, Pancreas Translational and Clinical Center, IRCCS Ospedale San Raffaele, Milano, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01151-yDOI Listing
December 2021

The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy With Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis.

Ann Surg 2021 11;274(5):721-728

Department of Surgery, Curry Cabral Hospital, CHLC, Lisbon, Portugal.

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers.

Summary Of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients.

Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018.

Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS.

Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005132DOI Listing
November 2021

Indications to total pancreatectomy for positive neck margin after partial pancreatectomy: a review of a slippery ground.

Updates Surg 2021 Aug 31;73(4):1219-1229. Epub 2021 Jul 31.

School of Medicine, Vita Salute San Raffaele University, Milan, Italy.

The extension of a partial pancreatectomy up to total pancreatectomy because of positive neck margin examined at intraoperative frozen section (IFS) analysis is an accepted procedure in modern pancreatic surgery with good accuracy. The goal of this practice is to improve the rate of radical (R0) resection in malignant tumors, mainly pancreatic ductal adenocarcinoma (PDAC), and to completely resect pre-invasive neoplasms such as intraductal papillary mucinous neoplasms (IPMNs). In the setting of IPMNs there is a consensus for pancreatic re-resection when high-grade dysplasia and invasive cancer are present at the neck margin. The presence of denudation is another indication for further resection in IPMNs. The role of IFS analysis in the management of pancreatic cancer is more debated. The presence of a positive intraoperative transection margin can be considered the surrogate of a biologically aggressive disease associated with a poorer prognosis. There are conflicting data regarding possible advantages of pancreatic re-resection up to total pancreatectomy, and the lack of randomized trials comparing different strategies does not offer a definitive answer. The goal of this review is to provide an up-to-date overview of the role IFS analysis of pancreatic margin and of pancreatic re-resection up to total pancreatectomy considering different pancreatic tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01141-0DOI Listing
August 2021

Total pancreatectomy sequelae and quality of life: results of islet autotransplantation as a possible mitigation strategy.

Updates Surg 2021 Aug 28;73(4):1237-1246. Epub 2021 Jul 28.

Chirurgia del Pancreas, Pancreas Translational and Clinical Center, IRCCS Ospedale San Raffaele, Milano, Italy.

Total pancreatectomy (TP) is a procedure weighed down not only by postoperative morbidity and mortality but also by long-term effects as a consequence of endocrine and exocrine pancreatic insufficiency. While the latter is now managed quite effectively with pancreatic enzyme replacement therapy, the former remains a challenge. The diabetes resulting after TP, with the complete loss of endogenous insulin and contraregulatory hormones, is characterized by important glycemic variations and is, therefore, frequently referred to as "brittle diabetes". One method to reduce the impact of brittle diabetes in patients undergoing TP is the re-infusion of autologous pancreatic islets isolated from the resected pancreas. Indications to islet autotransplantation (IAT), originally described for patients undergoing TP for chronic pancreatitis, have since been extended to selected patients with other benign and malignant diseases of pancreas. This review recaps on the literature regarding long-term postoperative complications, their impact on quality of life after TP and the role of IAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01129-wDOI Listing
August 2021

Preoperative risk stratification of postoperative pancreatic fistula: A risk-tree predictive model for pancreatoduodenectomy.

Surgery 2021 Jul 24. Epub 2021 Jul 24.

Department of General and Pancreatic Surgery, Verona University Hospital, Italy.

Background: Existing postoperative pancreatic fistula risk scores rely on intraoperative parameters, which limits their value in the preoperative setting. A preoperative predictive model to stratify the risk of developing postoperative pancreatic fistula before pancreatoduodenectomy was built and externally validated.

Methods: A regression risk-tree model for preoperative postoperative pancreatic fistula risk stratification was developed in the Verona University Hospital training cohort using preoperative variables and then tested prospectively in a validation cohort of patients who underwent pancreatoduodenectomy at San Raffaele Hospital of Milan.

Results: In the study period 566 (training cohort) and 456 (validation cohort) patients underwent pancreatoduodenectomy. In the multivariable analysis body mass index, radiographic main pancreatic duct diameter and American Society of Anesthesiologists score ≥3 were independently associated with postoperative pancreatic fistula. The regression tree analysis allocated patients into 3 preoperative risk groups with an 8%, 21%, and 32% risk of postoperative pancreatic fistula (all P < .01) based on main pancreatic duct diameter (≥ or <5 mm) and body mass index (≥ or <25). The 3 groups were labeled low, intermediate, and high risk and consisted of 206 (37%), 188 (33%), and 172 (30%) patients, respectively. The risk-tree was applied to validation cohort, successfully reproducing 3 risk groups with significantly different postoperative pancreatic fistula risks (all P < .01).

Conclusion: In candidates for pancreatoduodenectomy, the risk of postoperative pancreatic fistula can be quickly and accurately determined in the preoperative setting based on the body mass index and main pancreatic duct diameter at radiology. Preoperative risk stratification could potentially guide clinical decision-making, improve patient counseling and allow the establishment of personalized preoperative protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2021.06.046DOI Listing
July 2021

Total pancreatectomy: how, when and why?

Authors:
Massimo Falconi

Updates Surg 2021 Aug 20;73(4):1203-1204. Epub 2021 Jul 20.

School of Medicine, Vita Salute San Raffaele University, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13304-021-01134-zDOI Listing
August 2021

Outcomes After Minimally Invasive Versus Open Total Pancreatectomy: A Pan-European Propensity Score Matched Study.

Ann Surg 2021 Jul 14. Epub 2021 Jul 14.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands Department of Oncology and Robotic Surgery, Careggi University Hospital, Florence, Italy Department of Pancreatic Surgery, Scientific Institute San Raffaele Hospital, Milan, Italy DIMEC, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Department of Digestive and minimally invasive oncologic surgery, CHU Montpellier, Montpelier, France Department of Oncologic and Mininvasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy Department of General Surgery, Gazi University, School of Medicine, Ankara, Turkey Department of High-tech surgery, Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russia Division of General and Transplant Surgery, University of Pisa, Pisa, Italy Department of Surgery, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy Department of Surgery, UKSH Campus Lübeck, Lübeck, Germany Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France Department of Surgery, Hospital del Mar, Barcelona, Spain.

Objective: To assess postoperative 90-day outcomes after minimally invasive (laparoscopic/robot-assisted) total pancreatectomy (MITP) in selected patients versus open total pancreatectomy (OTP) among European centers.

Background: Minimally invasive pancreatic surgery is becoming increasingly popular but data on MITP are scarce and multicenter studies comparing outcomes versus OTP are lacking. It therefore remains unclear if MITP is a valid alternative.

Methods: Multicenter retrospective propensity-score matched study including consecutive adult patients undergoing MITP or OTP for all indications at 16 European centers in 7 countries (2008-2017). Patients after MITP were matched (1:1, caliper 0.02) to OTP controls. Missing data were imputed. The primary outcome was 90-day major morbidity (Clavien-Dindo ≥3a). Secondary outcomes included 90-day mortality, length of hospital stay, and survival.

Results: Of 361 patients (99 MITP/262 OTP), 70 MITP procedures (50 laparoscopic, 15 robotic, 5 hybrid) could be matched to 70 OTP controls. After matching, MITP was associated with a lower rate of major morbidity (17% MITP vs 31% OTP, P = 0.022). The 90-day mortality (1.4% MITP vs 7.1% OTP, P = 0.209) and median hospital stay (17 [IQR 11-24] MITP vs 12 [10-23] days OTP, P = 0.876) did not differ significantly. Among 81 patients with PDAC, overall survival was 3.7 (IQR 1.7-N/A) vs 0.9 (IQR 0.5-N/A) years, for MITP vs OTP, which was non-significant after stratification by T-stage.

Conclusion: This international propensity score matched study showed that MITP may be a valuable alternative to OTP in selected patients, given the associated lower rate of major morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005075DOI Listing
July 2021

Long-Term Survivors after Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival.

Ann Surg Oncol 2021 Dec 13;28(13):8249-8260. Epub 2021 Jul 13.

Division of Pancreatic Surgery, Department of Surgery, Pancreas Translational and Clinical Research Center, Università Vita-Salute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Data on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC.

Methods: Data from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival > 5 years were searched.

Results: Of the 176 patients included in this study, 48 (27%) were alive at 5 years, but only 20 (11%) had no recurrence. Median PRS was 12 months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (< 12 months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis > 200 U/mL, total pancreatectomy, N + status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival > 5 years.

Conclusion: More than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5 years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10401-7DOI Listing
December 2021

ASO Author Reflections: Long-Term Survivors after Upfront Resection for Pancreatic Cancer: Do They Really Exist?

Ann Surg Oncol 2021 12 10;28(13):8261-8262. Epub 2021 Jul 10.

Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Università Vita- Salute, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10402-6DOI Listing
December 2021

Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis.

Pancreatology 2021 Oct 3;21(7):1395-1401. Epub 2021 Jul 3.

Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment.

Methods: The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates.

Results: Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5-93.9) with no heterogeneity (I = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5-40.3) with moderate heterogeneity (I = 51%). A higher rate of relapse (35.9%, 95%CI 17.3-60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8-53) with substantial heterogeneity (I = 73.6%). No publication bias was observed.

Conclusion: Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2021.06.009DOI Listing
October 2021

Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy.

Ann Surg 2021 09;274(3):481-490

Wren Laboratories, Branford, CT.

Introduction: Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive, and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence.

Methods: Multicenter evaluation of NET resections over 24 months (n = 103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0 (83), R1/R2 (20). One millilitre of blood was collected at D0 and posroperative day (POD) 30. Transcript quantification by polymerase chain reaction (normal: ≤20), CgA by NEOLISA (normal ≤108 ng/mL). Standard-of-care (SoC) follow-up costs were calculated and compared to POD30 NETest-stratification approach. Analyses: Wilcoxon-paired test, Chi-square test.

Results:

D Biomarkers: NETest: 103 of 103 (100%)-positive, whereas 23 of 103 (22%) were CgA-positive (Chi-square = 78, P < 0.0001).In the R0 group, the NETest decreased 59 ± 28 to 26 ± 23 (P < 0.0001); 36% (30/83) remained elevated. No significant decrease was evident for CgA. In the R1/R2 group the NETest decreased but 100% remained elevated. CgA levels did not decrease.An elevated POD30 NETest was present in R0 and 25 (83%) developed radiological recurrences. Normal score R0 s (n = 53) did not develop recurrence (Chi-square = 56, P < 0.0001). Recurrence prediction was 94% accurate with the NETest.

Cost Evaluation: Using the NETest to stratify postoperative imaging resulted in a cost-savings of 42%.

Conclusion: NETest diagnosis is more accurate than CgA (100% vs 22%). Surgery significantly decreased NETest. An elevated POD30 NETest predicted recurrence with 94% accuracy and post-surgical POD30 NETest follow-up stratification decreased costs by 42%. CgA had no surgical utility. Further studies would define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005026DOI Listing
September 2021

Utility of the "2019 ACR/EULAR classification criteria" for the management of patients with IgG4-related disease.

Semin Arthritis Rheum 2021 08 8;51(4):761-765. Epub 2021 May 8.

Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.

Background: The 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.

Objective: To validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.

Methods: Four experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.

Results: Among the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p<0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.

Conclusions: The ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2021.04.021DOI Listing
August 2021

Proclivity to Explore Locally Advanced Pancreas Cancer Is Not Associated with Surgeon Volume.

J Gastrointest Surg 2021 10 23;25(10):2562-2571. Epub 2021 May 23.

Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, 986880 Nebraska Medical Center, Omaha, NE, 68198, USA.

Background And Purpose: There is limited high-level evidence to guide locally advanced pancreas cancer (LAPC) management. Recent work shows that surgeons' preferences in LAPC management vary broadly. We sought to examine whether surgeon volume was associated with attitudes regarding LAPC management.

Methods: An electronic survey was distributed by email to an international cohort of pancreas surgeons to evaluate practice patterns regarding LAPC management. Clinical vignette-based questions evaluated surgeons' attitudes regarding patient eligibility and the proclivity to offer exploration. Surgeons were classified into "low-" or "high-volume" categories according to thresholds of self-reported annual pancreatectomy volume. Surgeon's attitudes regarding LAPC management and inclination to consider exploration were compared across annual volume categories.

Results: A total of 153 eligible responses were received from 4 continents, for an estimated response rate of 10.6%. Median duration of practice was 12 years (IQR 6-20). Most respondents reported >25 cases/year (89, 58.2%), of which 34 (22.2%) reported >50. Compared to surgeons with <25 cases/year, surgeons with >25 cases/year practiced longer (median 15 vs. 7.5 years, P<0.001) and were more likely to "always" recommend neoadjuvant chemotherapy (83.2% vs. 56.3%, P=0.001). Surgeons performing >50 cases/year were more likely to offer arterial resection (70.6% vs. 43.7%, P=0.006). The willingness to offer (or defer) exploration did not differ across any categories of surgeons' annual case volume.

Conclusions: In an international survey of pancreas surgeons, the proclivity to consider exploration for LAPC was not associated with multiple categories of surgeon volume. Better evidence is needed to define the optimal management approach to LAPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-021-05034-wDOI Listing
October 2021

Does chronic consumption of angiotensin-converting enzyme inhibitors affect survival after surgical resection of pancreatic ductal adenocarcinoma?

Dig Liver Dis 2021 Aug 16;53(8):1065-1067. Epub 2021 May 16.

Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Via Olgettina 60, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2021.04.027DOI Listing
August 2021

Early Identification of Residual Disease After Neuroendocrine Tumor Resection Using a Liquid Biopsy Multigenomic mRNA Signature (NETest).

Ann Surg Oncol 2021 Nov 18;28(12):7506-7517. Epub 2021 May 18.

Wren Laboratories, Branford, CT, USA.

Introduction: Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence.

Methods: This was a multicenter evaluation of surgically treated primary NETs (n = 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0-100; normal ≤20). Statistical analyses were performed using the Mann-Whitney U-test, Chi-square test, Kaplan-Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean ± standard deviation.

Results: The NET cohort (n = 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (n = 102) and R1 and R2 (n = 51) resection. The mean follow-up time was 14 months (range 3-68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 ± 28). In the R0 cohort, POD30 levels decreased from 62 ± 28 to 22 ± 20 (p < 0.0001), but remained elevated in 30% (31/102) of patients: 28% lung, 29% pancreas, 27% small bowel, and 33% gastric. By 18 months, 25/31 (81%) patients with a POD30 NETest >20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1, p < 0.0001). AUROC analysis identified an AUC of 0.97 (p < 0.0001) for recurrence-prediction. In the R1 (n = 29) and R2 (n = 22) cohorts, the score decreased (R1: 74 ± 28 to 45 ± 24, p = 0.0012; R2: 72 ± 24 to 60 ± 28, p = non-significant). At POD30, 100% of NETest scores were elevated despite surgery (p < 0.0001).

Conclusion: The preoperative NETest accurately identified all NETs (100%). All resections decreased NETest levels and a POD30 NETest score >20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10021-1DOI Listing
November 2021

Understanding the Meaning of Recovery to Patients Undergoing Abdominal Surgery.

JAMA Surg 2021 Aug;156(8):758-765

Steinberg-Bernstein Centre for Minimally Invasive Surgery and Innovation, McGill University Health Centre, Montreal, Québec, Canada.

Importance: Postoperative recovery is difficult to define or measure. Research addressing interventions aimed to improve recovery after abdominal surgery often focuses on measures such as duration of hospital stay and complication rates. Although these clinical parameters are relevant, understanding patients' perspectives regarding postoperative recovery is fundamental to guiding patient-centered care.

Objective: To elucidate the meaning of recovery from the perspective of patients undergoing abdominal surgery.

Design, Setting, And Participants: This international qualitative study involved semistructured interviews with patients recovering from abdominal surgery from October 2016 to November 2018 in tertiary hospitals in 4 countries (Canada, Italy, Brazil, and Japan). A purposive maximal variation sampling method was used to ensure the recruitment of patients with varying demographic, clinical, and surgical characteristics. Data on race were not collected. Each interview lasted between 1 and 2 hours. Interviews were recorded and then transcribed verbatim. Transcripts were then analyzed using an inductive thematic analysis approach. Data analysis was conducted from July 2019 to September 2019.

Main Outcomes And Measures: The qualitative analysis revealed themes reflecting the meaning of recovery from the perspective of patients undergoing abdominal surgery.

Results: Thirty patients recovering from abdominal surgery were interviewed (15 [50%] female; mean [SD] age, 57 [18] years; 10 [33%] underwent major surgery; 16 [53%] underwent laparoscopic surgery). The interviews revealed that for patients undergoing abdominal surgery, the meaning of recovery embodied 5 overarching themes: (1) returning to habits and routines, (2) resolution of symptoms, (3) overcoming mental strains, (4) regaining independence, and (5) enjoying life. Themes associating the meaning of recovery to traditional parameters, such as earlier hospital discharge or absence of complications, were not identified in the interviews.

Conclusions And Relevance: This qualitative study suggests that the meaning of recovery from the perspective of patients undergoing abdominal surgery goes beyond traditional clinical parameters. The elements of recovery identified in this study should be taken into account in patient-surgeon discussions about recovery and when developing patient-centered strategies to improve postoperative outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2021.1557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117063PMC
August 2021

Impact of care pathway adherence on recovery following distal pancreatectomy within an enhanced recovery program.

HPB (Oxford) 2021 Apr 27. Epub 2021 Apr 27.

Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Background: In bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP).

Methods: Data for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions.

Results: Patients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08-1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to -2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13-1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73-4.54; p < 0.001).

Conclusion: Increased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2021.04.016DOI Listing
April 2021
-->