Publications by authors named "Riccardo Casadei"

172 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.
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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.
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http://dx.doi.org/10.1007/s13304-021-01171-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611384PMC
November 2021

Performance of EUS-FNB in solid pancreatic masses: a lesson from 463 consecutive procedures and a practical nomogram.

Updates Surg 2021 Oct 29. Epub 2021 Oct 29.

Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero, Universitaria Di Bologna, via Albertoni 15, Bologna, Italy.

The study's main goal was the diagnostic adequacy of pancreatic endoscopic ultrasonographic (EUS) fine-needle biopsy (FNB) and associated predictive factors. The secondary objective was to define the diagnostic accuracy of EUS-FNB in the diagnosis of pancreatic masses and pancreatic malignancies. None of the studies reported the diagnostic adequacy and accuracy of EUS. We retrospectively identified patients with solid pancreatic lesions that underwent EUS-FNB between 2013, and 2018. We calculated diagnostic adequacy and related factors. Using definitive histology on the surgically resected specimen as the gold standard, we calculated diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB. We identified a total of 463 procedures. Diagnostic specimens were adequate in 436 procedures (94.1%), while 27 biopsies provided insufficient samples (5.9%). The multivariate analysis showed that lesion size and needle caliper were the only factors influencing diagnostic adequacy. The use of a biopsy needle (OR 0.69, 95% CI 0.30-0.1.63, P 0.400) did not improve sample adequacy. We calculated sensitivity (100%), specificity (93.2%), diagnostic accuracy (93.2%), positive predictive value (97.1%), and negative predictive value (100%) using resected specimen as the gold standard. We found no significant complications. EUS-FNB is a reliable technique for the histological characterization of solid pancreatic masses.
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http://dx.doi.org/10.1007/s13304-021-01198-xDOI Listing
October 2021

Multimodal Strategy in Localized Merkel Cell Carcinoma: Where Are We and Where Are We Heading?

Int J Mol Sci 2021 Sep 30;22(19). Epub 2021 Sep 30.

Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence is rising. Multimodal treatment is crucial in the non-metastatic, potentially curable setting. However, the optimal management of patients with non-metastatic MCC is still unclear. In addition, novel insights into tumor biology and newly developed treatments (e.g., immune checkpoint inhibitors) that dramatically improved outcomes in the advanced setting are being investigated in earlier stages with promising results. Nevertheless, the combination of new strategies with consolidated ones needs to be clarified. We reviewed available evidence supporting the current treatment recommendations of localized MCC with a focus on potentially ground-breaking future strategies. Advantages and disadvantages of the different treatment modalities, including surgery, radiotherapy, chemotherapy, and immunotherapy in the non-metastatic setting, are analyzed, as well as those of different treatment modalities (adjuvant as opposed to neoadjuvant). Lastly, we provide an outlook of remarkable ongoing studies and of promising agents and strategies in the treatment of patients with non-metastatic MCC.
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http://dx.doi.org/10.3390/ijms221910629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508588PMC
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.
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http://dx.doi.org/10.1186/s13063-021-05506-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427847PMC
September 2021

Development and validation of a preoperative "difficulty score" for laparoscopic transabdominal adrenalectomy: a multicenter retrospective study.

Surg Endosc 2021 Aug 17. Epub 2021 Aug 17.

Surgical Clinic, Department of Clinical and Experimental Sciences, The University of Brescia at ASST Spedali Civili di Brescia, Brescia, Italy.

Background: A difficulty score for laparoscopic adrenalectomy (LA) is lacking in the literature. A retrospective cohort study was designed to develop a preoperative "difficulty score" for LA.

Methods: A multicenter study was conducted involving four Italian tertiary centers for adrenal disease. The population was randomly divided into two subsets: training group and validation one. A multicenter study was undertaken, including 964 patients. Patient, adrenal lesion, surgeon's characteristics, and the type of procedure were studied as potential predictors of target events. The operative time (pOT), conversion rate (cLA), or both were used as indicators of the difficulty in three multivariate models. All models were developed in a training cohort (70% of the sample) and validated using 30% of patients. For all models, the ability to predict complicated postoperative course was reported describing the area under the curve (AUCs). Logistic regression, reporting odds ratio (OR) with p-value, was used.

Results: In model A, gender (OR 2.04, p = 0.001), BMI (OR 1.07, p = 0.002), previous surgery (OR 1.29, p = 0.048), site (OR 21.8, p < 0.001) and size of the lesion (OR 1.16, p = 0.002), cumulative sum of procedures (OR 0.99, p < 0.001), extended (OR 26.72, p < 0.001) or associated procedures (OR 4.32, p = 0.015) increased the pOT. In model B, ASA (OR 2.86, p = 0.001), lesion size (OR 1.20, p = 0.005), and extended resection (OR 8.85, p = 0.007) increased the cLA risk. Model C had similar results to model A. All scores obtained predicted the target events in validation cohort (OR 1.99, p < 0.001; OR 1.37, p = 0.007; OR 1.70, p < 0.001, score A, B, and C, respectively). The AUCs in predicting complications were 0.740, 0.686, and 0.763 for model A, B, and C, respectively.

Conclusion: A difficulty score based on both pOT and cLA (Model C) was developed using 70% of the sample. The score was validated using a second cohort. Finally, the score was tested, and its results are able to predict a complicated postoperative course.
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http://dx.doi.org/10.1007/s00464-021-08678-6DOI Listing
August 2021

Contemporary indications for upfront total pancreatectomy.

Updates Surg 2021 Aug 14;73(4):1205-1217. Epub 2021 Aug 14.

Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Via Massarenti n.9, 40138, Bologna, Italy.

Currently, advances in surgical techniques, improvements in perioperative care, new formulations of intermediate and long-acting insulin and of modern pancreatic enzyme preparations have allowed obtaining good short and long-term results and quality of life, especially in high-volume centres in performing total pancreatectomy (TP).Thus, the surgeon's fear in performing TP is not justified and total pancreatectomy can be considered a viable option in selected patients in high-volume centres. The aim of this review was to define the current indications for this procedure, in particular for upfront TP, considering not only the pancreatic disease, but also the surgical approach (open, mini-invasive) and the relationship with vascular resection.
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http://dx.doi.org/10.1007/s13304-021-01145-wDOI Listing
August 2021

Neoadjuvant Therapy for Resectable Pancreatic Cancer: A New Standard of Care. Pooled Data From 3 Randomized Controlled Trials.

Ann Surg 2021 11;274(5):713-720

Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.

Objective: The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome.

Summary Background Data: Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations.

Methods: Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards.

Results: A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters.

Conclusion: Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.
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http://dx.doi.org/10.1097/SLA.0000000000005126DOI Listing
November 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.
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http://dx.doi.org/10.1097/SLA.0000000000005075DOI Listing
July 2021

Prophylactic cholecystectomy is not mandatory in patients candidate to the resection for small intestine neuroendocrine neoplasms: a propensity score-matched and cost-minimization analysis.

Updates Surg 2021 Jul 5. Epub 2021 Jul 5.

Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, Bologna, Italy.

To evaluate two competitive strategies in patients undergoing resection of Small-intestine neuroendocrine neoplasms (Si-NEN): prophylactic cholecystectomy (PC) versus On-demand delayed (OC) cholecystectomy. None comparative studies are available. This is a retrospective study based on 247 Si-NENs candidates for the primary tumor resection. Patients were divided into two arms: PC and OC. Propensity score matching was performed, reporting the d value. The primary outcome was the rehospitalization rate for any cause. The secondary endpoints were: the rehospitalization rate for biliary stone disease (BSD), the mean number of rehospitalization (any cause and BSD), the complication rate (all and severe). A P value < 0.05 was considered significant, and the number needed to treat (NNT) < 10 was considered clinically relevant. Before matching, 52 (21.1%) were in the PC arm and 195 (78.9%) in the OC group. The two arms have a sub-optimal balance for age (d = 0.575), symptoms (d = 0.661), ENETS TNM stage (d = 0.661). After matching, we included 52 patients in PC and 104 in OC one. The two groups are well balanced (all d values < 0.5). The rehospitalization rate was similar in the two groups (36% vs 31; P = 0.594; NNT = 21). The rehospitalization rate for BSD was lower in the PC arm than OC one (0% vs 7%) without statistical significance (P = 0.096) and relevance (NNT = 15). The mean number of readmission (any cause and BSD) and the complication rate (all and severe) were similar. PC was not mandatory in patients having Si-NEN and candidates to the resection of primary tumors.
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http://dx.doi.org/10.1007/s13304-021-01123-2DOI Listing
July 2021

Effect of Mobile Carrier on the Performance of PVAm-Nanocellulose Facilitated Transport Membranes for CO Capture.

Membranes (Basel) 2021 Jun 12;11(6). Epub 2021 Jun 12.

Dipartimento di Ingegneria Civile, Chimica, Ambientale e dei Materiali (DICAM), Alma Mater Studiorum-Università di Bologna, Via Terracini, 28, 40131 Bologna, Italy.

Facilitated transport membranes obtained by coupling polyvinylamine with highly charged carboxymethylated nanocellulose fibers were studied considering both water sorption and gas permeation experiments. In particular, the effect of the L-arginine as a mobile carrier was investigated to understand possible improvements in CO transport across the membranes. The results show that L-arginine addition decreases the water uptake of the membrane, due to the lower polyvinylamine content, but was able to improve the CO transport. Tests carried on at 35 °C and high relative humidity indeed showed an increase of both CO permeability and selectivity with respect to nitrogen and methane. In particular, the CO permeability increased from 160 to about 340 Barrer when arginine loading was increased from 0 to 45 wt%. In the same conditions, selectivity with respect to nitrogen was more than doubled, increasing from 20 to 45. Minor improvements were instead obtained with respect to methane; CO/CH selectivity, indeed, even in presence of the mobile carrier, was limited to about 20.
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http://dx.doi.org/10.3390/membranes11060442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231264PMC
June 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.
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http://dx.doi.org/10.1097/SLA.0000000000004963DOI Listing
June 2021

A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

Diagnostics (Basel) 2021 May 12;11(5). Epub 2021 May 12.

Department of Nuclear Medicine, DIMES, Alma Mater Studiorum, University of Bologna, I-40126 Bologna, Italy.

Predicting grade 1 (G1) and 2 (G2) primary pancreatic neuroendocrine tumour (panNET) is crucial to foresee panNET clinical behaviour. Fifty-one patients with G1-G2 primary panNET demonstrated by pre-surgical [68Ga]Ga-DOTANOC PET/CT and diagnostic conventional imaging were grouped according to the tumour grade assessment method: histology on the whole excised primary lesion (HS) or biopsy (BS). First-order and second-order radiomic features (RFs) were computed from SUV maps for the whole tumour volume on HS. The RFs showing the lowest -values and the highest area under the curve (AUC) were selected. Three radiomic models were assessed: A (trained on HS, validated on BS), B (trained on BS, validated on HS), and C (using the cross-validation on the whole dataset). The second-order normalized homogeneity and entropy was the most effective RFs couple predicting G2 and G1. The best performance was achieved by model A (test AUC = 0.90, sensitivity = 0.88, specificity = 0.89), followed by model C (median test AUC = 0.87, sensitivity = 0.83, specificity = 0.82). Model B performed worse. Using HS to train a radiomic model leads to the best prediction, although a "hybrid" (HS+BS) population performs better than biopsy-only. The non-invasive prediction of panNET grading may be especially useful in lesions not amenable to biopsy while [68Ga]Ga-DOTANOC heterogeneity might recommend FDG PET/CT.
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http://dx.doi.org/10.3390/diagnostics11050870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150289PMC
May 2021

Evaluation of cost-effectiveness among open, laparoscopic and robotic distal pancreatectomy: A systematic review and meta-analysis.

Am J Surg 2021 Sep 7;222(3):513-520. Epub 2021 Apr 7.

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

Background: The cost-effectiveness of minimally invasive distal pancreatectomy (MIDP) is still a matter of debate. This study compares the cost-effectiveness of open (ODP), laparoscopic (LDP) and robotic distal pancreatectomy (RDP).

Methods: Pubmed, Web of Science and Cochrane Library databases were searched. Studies comparing cost-effectiveness of ODP and MIDP were included.

Results: A total of 1052 titles were screened and 16 articles were included in the study, 2431 patients in total. LDP resulted the most cost-efficient procedure, with a mean total cost of 14,682 ± 5665 € and the lowest readmission rates. ODP had lower surgical procedure costs, 3867 ± 768 €. RDP was the safest approach regarding hospital stay costs (5239 ± 1741 €), length of hospital stay, morbidity, clinically relevant pancreatic fistula and reoperations.

Conclusion: In this meta-analysis MIDP resulted as the most cost-effective approach. LDP seems to be protective against high costs, but RDP seems to be safer.
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http://dx.doi.org/10.1016/j.amjsurg.2021.03.066DOI Listing
September 2021

Percutaneous management of postoperative Bile leak after hepato-pancreato-biliary surgery: a multi-center experience.

HPB (Oxford) 2021 Oct 19;23(10):1518-1524. Epub 2021 Mar 19.

Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138, Bologna, Italy.

Background: Bile leak (BL) after hepato-pancreato-biliary (HPB) surgery is associated with significant morbidity and mortality. Aim of this study was to evaluate effectiveness and safety of percutaneous transhepatic approach (PTA) to drainage BL after HPB surgery.

Methods: Between 2006 and 2018, consecutive patients who were referred to interventional radiology units of three tertiary referral hospitals were retrospectively identified. Technical success and clinical success were analyzed and evaluated according to surgery type, BL-site and grade, catheter size and biochemical variables. Complications of PTA were reported.

Results: One-hundred-eighty-five patients underwent PTA for BL. Technical success was 100%. Clinical success was 78% with a median (range) resolution time of 21 (5-221) days. Increased clinical success was associated with patients who underwent hepaticresection (86%,p = 0,168) or cholecystectomy (86%,p = 0,112) while low success rate was associated to liver-transplantation (56%,p < 0,001). BL-site,grade, catheter size and AST/ALT levels were not associated with clinical success. ALT/AST high levels were correlated to short time resolution (17 vs 25 days, p = 0,037 and 16 vs 25 day, p = 0,011, respectively) Complications of PTA were documented in 21 (11%) patients.

Conclusion: This study based on a large cohort of patients demonstrated that PTA is a valid and safe approach in BL treatment after HPB surgery.
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http://dx.doi.org/10.1016/j.hpb.2021.02.014DOI Listing
October 2021

Laparoscopic versus open distal pancreatectomy: a single centre propensity score matching analysis.

Updates Surg 2021 Oct 3;73(5):1747-1755. Epub 2021 Apr 3.

Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.

The laparoscopic approach is considered as standard practice in patients with body-tail pancreatic neoplasms. However, only a few randomized controlled trials (RCTs) and propensity score matching (PSM) studies have been performed. Thus, additional studies are needed to obtain more robust evidence. This is a single-centre propensity score-matched study including patients who underwent laparoscopic (LDP) and open distal pancreatectomy (ODP) with splenectomy for pancreatic neoplasms. Demographic, intra, postoperative and oncological data were collected. The primary endpoint was the length of hospital stay. The secondary endpoints included the assessment of the operative findings, postoperative outcomes, oncological outcomes (only in the subset of patients with pancreatic ductal adenocarcinoma-PDAC) and total costs. In total, 205 patients were analysed: 105 (51.2%) undergoing an open approach and 100 (48.8%) a laparoscopic approach. After PSM, two well-balanced groups of 75 patients were analysed and showed a shorter length of hospital stay (P = 0.001), a lower blood loss (P = 0.032), a reduced rate of postoperative morbidity (P < 0.001) and decreased total costs (P = 0.050) after LDP with respect to ODP. Regarding the subset of patients with PDAC, 22 patients were analysed: they showed a significant shorter length of hospital stay (P = 0.050) and a reduction in postoperative morbidity (P < 0.001) after LDP with respect to ODP. Oncological outcomes were similar. LDP showed lower hospital stay and postoperative morbidity rate than ODP both in the entire population and in patients affected by PDAC. Total costs were reduced only in the entire population. Oncological outcomes were comparable in PDAC patients.
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http://dx.doi.org/10.1007/s13304-021-01039-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500861PMC
October 2021

Blumgart Anastomosis After Pancreaticoduodenectomy. A Comprehensive Systematic Review, Meta-Analysis, and Meta-Regression.

World J Surg 2021 06 15;45(6):1929-1939. Epub 2021 Mar 15.

Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, , S.Orsola-Malpighi Hospital, University of Bologna, Policlinico S.Orsola-Malpighi Via Massarenti n.9, 40138, Bologna, Italy.

Background: The superiority of Blumgart anastomosis (BA) over non-BA duct to mucosa (non-BA DtoM) still remains under debate.

Methods: We performed a systematic search of studies comparing BA to non-BA DtoM. The primary endpoint was CR-POPF. Postoperative morbidity and mortality, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate, and length of stay (LOS) were evaluated as secondary endpoints. The meta-analysis was carried out using random effect. The results were reported as odds ratio (OR), risk difference (RD), weighted mean difference (WMD), and number needed to treat (NNT).

Results: Twelve papers involving 2368 patients: 1075 BA and 1193 non-BA DtoM were included. Regarding the primary endpoint, BA was superior to non-BA DtoM (RD = 0.10; 95% CI: -0.16 to -0.04; NNT = 9). The multivariate ORs' meta-analysis confirmed BA's protective role (OR 0.26; 95% CI: 0.09 to 0.79). BA was superior to DtoM regarding overall morbidity (RD = -0.10; 95% CI: -0.18 to -0.02; NNT = 25), PPH (RD = -0.03; 95% CI -0.06 to -0.01; NNT = 33), and LOS (- 4.2 days; -7.1 to -1.2 95% CI).

Conclusion: BA seems to be superior to non-BA DtoM in avoiding CR-POPF.
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http://dx.doi.org/10.1007/s00268-021-06039-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093149PMC
June 2021

External validation of nomogram for predicting malignant intraductal papillary mucinous neoplasm (IPMN): from the theory to the clinical practice using the decision curve analysis model.

Updates Surg 2021 Apr 23;73(2):429-438. Epub 2021 Feb 23.

Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Via Massarenti n.9, 40138, Bologna, Italy.

The management of IPMNs is a challenging and controversial issue because the risk of malignancy is difficult to predict. The present study aimed to assess the clinical usefulness of two preoperative nomograms for predicting malignancy of IPMNs allowing their proper management. Retrospective study of patients affected by IPMNs. Two nomograms, regarding main (MD) and branch duct (BD) IPMN, respectively, were evaluated. Only patients who underwent pancreatic resection were collected to test the nomograms because a pathological diagnosis was available. The analysis included: 1-logistic regression analysis to calibrate the nomograms; 2-decision curve analysis (DCA) to test the nomograms concerning their clinical usefulness. 98 patients underwent pancreatic resection. The logistic regression showed that, increasing the score of both the MD-IPMN and BD-IPMN nomograms, significantly increases the probability of IPMN high grade or invasive carcinoma (P = 0.029 and P = 0.033, respectively). DCA of MD-IPMN nomogram showed that there were no net benefits with respect to surgical resection in all cases. DCA of BD-IPMN nomogram, showed a net benefit only for threshold probability between 40 and 60%. For these values, useless pancreatic resection should be avoided in 14.8%. The two nomograms allowed a reliable assessment of the malignancy rate. Their clinical usefulness is limited to BD-IPMN with threshold probability of malignancy of 40-60%, in which the patients can be selected better than the "treat all" strategy.
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http://dx.doi.org/10.1007/s13304-021-00999-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005398PMC
April 2021

Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

Cancers (Basel) 2021 Jan 19;13(2). Epub 2021 Jan 19.

Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria Di Bologna, via Albertoni 15, 40138 Bologna, Italy.

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP-NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3-4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with Lu-Dotatate.
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http://dx.doi.org/10.3390/cancers13020358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835931PMC
January 2021

Improved survival after pancreatic re-resection of positive neck margin in pancreatic cancer patients. A systematic review and network meta-analysis.

Eur J Surg Oncol 2021 Jun 13;47(6):1258-1266. Epub 2021 Jan 13.

Vita Salute San Raffaele University Milan, Italy; Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.

The oncological benefit of achieving a negative pancreatic neck margin through re-resection after a positive frozen section (FS) is debated. Aim of this network meta-analysis is to evaluate the survival benefit of re-resection after intraoperative FS neck margin examination following pancreatectomy for ductal adenocarcinoma. A systematic search of studies comparing different strategies for the management of positive FS was performed. Patients were classified in three groups based on FS and permanent section (PS): Group A (FS-, PS-R0), Group B (FS+, PS-R0), Group C (FS±, PS-R1). A frequent random-effects network-meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). Primary endpoint was overall survival (OS). Secondary endpoints were pathological outcomes. Seven retrospectives studies with 4205 patients were included and 99.1% of the pancreatic resections were pancreatoduodenectomies. Group A had the highest probability of better OS (SUCRA = 90%), compared to Group B (SUCRA = 48.7%) and Group C, which was the worst prognostic scenario (SUCRA = 11.3%). Group B had still a probability of longer OS compared to Group C (SUCRA = 48.7% vs 11.3%). Pathological features were more favourable in Group A, with the highest SUCRA for T1-T2 tumors (92.6%), N0 status (89.4%), absence of perineural invasion (92.3%). Heterogeneity was low (τ-value <0.1) for OS, and moderate (τ-values: 0.1-0.6) for pT, pN, and perineural invasion. In conclusion, negative neck margin after primary resection (FS negative) or re-resection of a positive FS was associated with improved survival compared with PS-R1. However, any intraoperative positive FS can be considered as a prognostic factor associated with a more aggressive disease.
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http://dx.doi.org/10.1016/j.ejso.2021.01.001DOI Listing
June 2021

Pancreatic mucinous cystadenocarcinoma in a patient harbouring germline mutation effectively treated with olaparib: A case report.

World J Gastrointest Oncol 2020 Dec;12(12):1456-1463

Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria Di Bologna, Bologna 40138, Italy.

Background: Pancreatic mucinous cystadenocarcinoma (MCAC) is a rare malignancy with a poor prognosis when it presents metastases at diagnosis. Due to its very low incidence, there are no clear recommendations for the treatment of advanced disease. Olaparib (an oral PARP inhibitor) has been approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma harbouring germline / mutations. Herein, we report the first case of a germline mutated unresectable MCAC which was effectively treated with olaparib.

Case Summary: A 41-year-old woman, without personal or family history of cancer, was diagnosed with ovarian and peritoneal metastases of MCAC. She underwent 12 cycles of gemcitabine plus oxaliplatin (GEMOX) obtaining a partial response and allowing radical surgery. One year later, local recurrence was documented, and other 12 cycles of GEMOX were administered obtaining a complete response. Seven years later, another local recurrence, not amenable to surgical resection, was diagnosed. She started FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and fluorouracil), obtaining a partial response after 8 cycles. Given the excellent response to platinum-based chemotherapy, testing was performed, and a germline mutation was detected. She was switched to maintenance olaparib due to chemotherapy-related toxicities and achieved an almost complete metabolic response, with a reduction in the diameter of the lesion, after three months of therapy.

Conclusion: The current case suggests the beneficial effect of olaparib in mutated MCAC. However, further studies are required
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http://dx.doi.org/10.4251/wjgo.v12.i12.1456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739147PMC
December 2020

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches.

World J Gastroenterol 2020 Nov;26(42):6529-6555

Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy.

The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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http://dx.doi.org/10.3748/wjg.v26.i42.6529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673966PMC
November 2020

Is Ultrasound Elastography Useful in Predicting Clinically Relevant Pancreatic Fistula After Pancreatic Resection?: A Systematic Review and Meta-analysis.

Pancreas 2020 Nov/Dec;49(10):1342-1347

From the Azienda Ospedaliero-Universitaria di Bologna, Bologna.

Objectives: Ultrasound (US) elastography has been proposed for the non-invasive prediction of clinically relevant pancreatic fistula (CR-POPF) in patients undergoing pancreatic resection. We aimed to perform a systematic review with meta-analysis to assess the diagnostic value of US elastography in predicting CR-POPF.

Methods: MEDLINE via PubMed, Ovid Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to April 20, 2020. Studies assessing the performance of abdominal US elastography in predicting CR-POPF in patients undergoing pancreatic resection were included. The quality of the studies was assessed using Quality Assessment of Diagnostic Accuracy Studies.

Results: Five studies, including 247 patients who underwent partial pancreatic resection of whom 72 patients experiencing CR-POPF, were selected. All studies performed US elastography in different pancreatic sites. The pooled mean strain value was lower in pancreatic segments of patients experiencing CR-POPF than in those without, with a pooled weighted mean difference of -0.187 (95% confidence intervals, -0.303 to -0.071; P = 0.002). There was low heterogeneity between studies (I = 7.6%), and all studies were at "high risk" or "unclear risk" of bias.

Conclusions: This study provides evidence that US elastography values are statistically significantly lower in patients experiencing CR-POPF.
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http://dx.doi.org/10.1097/MPA.0000000000001685DOI Listing
September 2021

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature.

World J Clin Cases 2020 Oct;8(19):4450-4465

Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy.

Background: The therapeutic approach of metastatic renal cell carcinoma (RCC) represents a real challenge for clinicians, because of the variable clinical course; the recent availability of numerous targeted therapies that have significantly improved overall oncological results, but still with a low percentage of complete responses; and the increasing role of metastasectomy (MSX) as an effective strategy to achieve a durable cure, or at least defer initiation of systemic therapies, in selected patients and in the context of multimodality treatment strategies.

Case Summary: We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC; he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy, with subsequent systemic therapy with Fluorouracil, Interferon-alpha and Interleukin 2. The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences, successfully treated with multiple systemic treatments, repeated local treatments, including two pancreatic resections, conservative resection and ablation of multiple bilobar liver metastases, resection and stereotactic body radiotherapy of multiple lung metastases. He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites, including resection of more than 38 metastases, and 5 years after his last MSX.

Conclusion: This case highlights that effective multimodality therapeutic strategies, including multiple systemic treatments and iterative aggressive surgical resection, can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.
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http://dx.doi.org/10.12998/wjcc.v8.i19.4450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559688PMC
October 2020

The Usefulness of a Preoperative Nomogram for Predicting the Probability of Conversion from Laparoscopic to Open Distal Pancreatectomy: A Single-Center Experience.

World J Surg 2021 Jan 15;45(1):252-260. Epub 2020 Oct 15.

Department of Internal Medicine and Surgery (DIMEC), S.Orsola-Malpighi Hospital, Alma Mater Studiorum-University of Bologna, Via Massarenti n.9, 40138, Bologna, Italy.

Background: Laparoscopic distal pancreatectomy (LDP) represents a challenging procedure with a high conversion rate. A nomogram is a simple statistical predictive tool which is superior to risk groups. The aim of this study was to develop and validate a preoperative nomogram for predicting the probability of conversion from laparoscopic to open distal pancreatectomy.

Methods: This is a retrospective study of 100 consecutive patients who underwent LDP. For each patient demographic, pre-intra- and postoperative data were collected. Univariate and multivariate analyses were carried out to identify the factors significantly influencing the conversion rate. The effect of each factor was weighted using the beta coefficient (β), and a nomogram was built. Finally, a logistic regression between the score and the conversion rate was carried out to calibrate the nomogram.

Results: The conversion rate was 19.0%. At multivariate analysis, female (β =  - 1.8 ± 0.9; P = 0.047) and tail location of the tumor (β =  - 2.1 ± 1.1; P = 0.050) were significantly related to a low probability of conversion. Body mass index (BMI) (β = 0.2 ± 0.1; P = 0.011) and subtotal pancreatectomy (β = 2.4 ± 0.9; P = 0.006) were factors independently related to a high probability of conversion. The nomogram constructed had a minimum value of 4 and a maximum value of 18 points. The probability of conversion increased significantly starting from a minimum score of 6 points (P = 0.029; conversion probability 14.4%; 95%CI, 1.5-27.3%) up to 16 (P = 0.048; 27.8%; 95%CI, 0.2-48.7%).

Conclusion: The nomogram proposed could serve as an effective preoperative tool capable of assessing the probability of conversion, allowing to take reliable decisions regarding indications and adequate stepwise training program of LDP.
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http://dx.doi.org/10.1007/s00268-020-05806-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752782PMC
January 2021

The use of comprehensive complication Index® in pancreatic surgery: a comparison with the Clavien-Dindo system in a high volume center.

HPB (Oxford) 2021 Apr 19;23(4):618-624. Epub 2020 Sep 19.

Division of Pancreatic Surgery, Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni 15, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Italy.

Background: The Clavien-Dindo classification (CDC) system and Comprehensive Complication Index (CCI®) are both widely used methods for reporting the burden of postoperative complications. This study aimed to compare the accuracy of the CDC and CCI® in predicting outcomes associated with pancreatic surgery.

Methods: The CCI® and CDC were applied to 668 patients who underwent pancreatic resection. Length of postoperative stay (LOS) was chosen as the primary outcome variable. The comparison between CCI® and CDC was made with the Spearman test, reporting þs with standard error (SE) and logistic regression, reporting the Odds Ratio (OR) and Area Under the Curve with SE.

Results: The median value with the interquartile range (IQR) of CCI® was 20.9 (0-29.6). Both CCI® (þs = 0.609) and CDC (0.590) were significantly (P < 0.001) correlated to LOS. CCI (OR 1.056 and OR 1.052) and CDC (OR 1.978, and OR 1.994) predicted (P < 0.001) LOS over the median and 75th percentile. The accuracy of CCI® was superior to CDC for LOS over 50th (0.785 vs. 0.740; P = 0.004) and over 75th (0.835 vs. 0.761; P < 0.001) percentile.

Conclusion: The accuracy of CCI® in measuring the complicated postoperative course was superior to CDC, correctly classifying eight patients every ten tested.
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http://dx.doi.org/10.1016/j.hpb.2020.09.002DOI Listing
April 2021

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

Pancreatology 2020 Oct 22;20(7):1323-1331. Epub 2020 Aug 22.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Background: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP.

Methods: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018.

Results: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality.

Conclusions: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.
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http://dx.doi.org/10.1016/j.pan.2020.08.009DOI Listing
October 2020

Pebax 2533/Graphene Oxide Nanocomposite Membranes for Carbon Capture.

Membranes (Basel) 2020 Aug 15;10(8). Epub 2020 Aug 15.

Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy.

In this work, the behavior of new GO-based mixed matrix membranes was tested in view of their use as CO-selective membrane in post combustion carbon capture applications. In particular, the new materials were obtained by mixing of Pebax 2533 copolymer with different types of graphene oxide (GO). Pebax 2533 has indeed lower selectivity, but higher permeability than Pebax 1657, which is more commonly used for membranes, and it could therefore benefit from the addition of GO, which is endowed with very high selectivity of CO with respect to nitrogen. The mixed matrix membranes were obtained by adding different amounts of GO, from 0.02 to 1% by weight, to the commercial block copolymers. Porous graphene oxide (PGO) and GO functionalized with polyetheramine (PEAGO) were also considered in composites produced with similar procedure, with a loading of 0.02%wt. The obtained films were then characterized by using SEM, DSC, XPS analysis and permeability experiments. In particular, permeation tests with pure CO and N at 35°C and 1 bar of upstream pressure were conducted for the different materials to evaluate their separation performance. It has been discovered that adding these GO-based nanofillers to Pebax 2533 matrix does not improve the ideal selectivity of the material, but it allows to increase CO permeability when a low filler content, not higher than 0.02 wt%, is considered. Among the different types of GO, then, porous GO seems the most promising as it shows CO permeability in the order of 400 barrer (with an increase of about 10% with respect to the unloaded block copolymer), obtained without reducing the CO/N selectivity of the materials, which remained in the order of 25.
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http://dx.doi.org/10.3390/membranes10080188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464092PMC
August 2020

The learning curve for the second generation of laparoscopic surgeons: lesson learned from a large series of laparoscopic adrenalectomies.

Surg Endosc 2021 06 17;35(6):2914-2920. Epub 2020 Jun 17.

Department of Medical and Surgical Science (DIMEC), University of Bologna, Alma Mater Studiorum, Bologna, Italy.

Background: Laparoscopic adrenalectomy has a well-demonstrated learning curve in the first generation of laparoscopic surgeons. Data about the second generation of laparoscopic surgeons are lacking.

Methods: In this retrospective observational study, data from patients undergoing laparoscopic adrenalectomy from 2000 to 2019 in a high-volume center were collected and analyzed. The cumulative sum of procedures of each surgeon and the operating time were evaluated. A multivariate analysis with backward stepwise logistic regression was carried out to define which factors influenced the operative time. Three surgeons performed the analyzed procedures: a senior surgeon who began his laparoscopic activity without receiving specific training or supervision and two young surgeons, who performed their procedures under the guidance of the "senior" experienced surgeon. The first 38 procedures of the three surgeons were then compared.

Results: A total of 244 laparoscopic adrenalectomies were performed. Age, clinical diagnosis, side of the lesion, body mass index, comorbidities, Charlson index, American Society of Anaesthesiologists (ASA) score, and lower abdominal surgery were found to have no significant relationship with the operative time (p > 0.05). Gender, symptoms, previous upper abdominal surgery, size of the lesion, and cumulative sum of procedures were independent predictors of operative time. In the comparison between different surgeons, operative time resulted significantly longer for the senior (165 min; 140-180) than for the two junior surgeons (137.5 min; 115-160; p = 0.003 and 130 min; 120-170; p = 0.001).

Conclusions: The presence of a mentor in operative theater and specific training programs could be useful during the learning period. The cumulative sum of procedures related to the operative time represents a good parameter to measure the acquired expertise of a surgeon.
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http://dx.doi.org/10.1007/s00464-020-07730-1DOI Listing
June 2021

Intraoperative electrochemotherapy in locally advanced pancreatic cancer: indications, techniques and results-a single-center experience.

Updates Surg 2020 Dec 12;72(4):1089-1096. Epub 2020 May 12.

Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, S.Orsola-Malpighi Hospital, University of Bologna, Via Massarenti n.9, 40138, Bologna, Italy.

Background: Locally advanced pancreatic cancer (LAPC) is usually treated with chemoradiotherapy with poor results. The aim of the study was to assess whether intraoperative electrochemotherapy could be proposed as additional therapy in treating LAPC.

Methods: Observational study of patients affected by LAPC who underwent intraoperative electrochemotherapy (ECT) after chemoradiotherapy. Data at diagnosis, at restaging and short and long-term outcomes, including assessment of quality of life, were collected for each patient.

Results: Five patients underwent ECT: in four cases, the tumours were located in the head and, in one, in the body of the pancreas. Preoperative chemotherapy consisted mainly of six cycles of modified Folfirinox. At restaging, the serum value of carbohydrate antigen (Ca 19-9) and tumour size were reduced; however, the vascular involvement did not change. No downstaging was recorded. The ECT procedure was performed using at least four needles with a mean duration time of 27 min (range 15-40). No postoperative mortality or major complications were reported. The mean length of stay (LOS) was 8 days (range 5-14). Four patients were alive and well at the end of the study, while one patient died from disease progression. The mean follow-up was 20.8 months (range 9-34) from diagnosis and 9.4 months (range 2-19) from ECT. The quality of life was good and there was improvement in pain/discomfort.

Conclusions: Electrochemotherapy could be proposed as a simple, feasible and safe palliative additional treatment in LAPC without progression after chemoradiotherapy. It seems to allow a good quality of life and pain improvement.
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http://dx.doi.org/10.1007/s13304-020-00782-xDOI Listing
December 2020
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