Publications by authors named "Giovanni Capretti"

46 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

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

Updates Surg 2021 Oct 1. Epub 2021 Oct 1.

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

Clinically relevant postoperative pancreatic fistula (CR-POPF) is a life-threatening complication following pancreaticoduodenectomy (PD). Individualized preoperative risk assessment could improve clinical management and prevent or mitigate adverse outcomes. The aim of this study is to develop a machine learning risk model to predict occurrence of CR-POPF after PD from preoperative computed tomography (CT) scans. A total of 100 preoperative high-quality CT scans of consecutive patients who underwent pancreaticoduodenectomy in our institution between 2011 and 2019 were analyzed. Radiomic and morphological features extracted from CT scans related to pancreatic anatomy and patient characteristics were included as variables. These data were then assessed by a machine learning classifier to assess the risk of developing CR-POPF. Among the 100 patients evaluated, 20 had CR-POPF. The predictive model based on logistic regression demonstrated specificity of 0.824 (0.133) and sensitivity of 0.571 (0.337), with an AUC of 0.807 (0.155), PPV of 0.468 (0.310) and NPV of 0.890 (0.084). The performance of the model minimally decreased utilizing a random forest approach, with specificity of 0.914 (0.106), sensitivity of 0.424 (0.346), AUC of 0.749 (0.209), PPV of 0.502 (0.414) and NPV of 0.869 (0.076). Interestingly, using the same data, the model was also able to predict postoperative overall complications and a postoperative length of stay over the median with AUCs of 0.690 (0.209) and 0.709 (0.160), respectively. These findings suggest that preoperative CT scans evaluated by machine learning may provide a novel set of information to help clinicians choose a tailored therapeutic pathway in patients candidated to pancreatoduodenectomy.
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http://dx.doi.org/10.1007/s13304-021-01174-5DOI Listing
October 2021

Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.

Front Genet 2021 30;12:693933. Epub 2021 Aug 30.

Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children's Hospital, Florence, Italy.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, = 3.03 × 10 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of , a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
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http://dx.doi.org/10.3389/fgene.2021.693933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435735PMC
August 2021

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

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

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

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

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

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

Conclusions: Patients with IPMN had a better prognosis than PDAC patients, regardless of disease stage.
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http://dx.doi.org/10.1016/j.dld.2021.06.006DOI Listing
July 2021

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

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

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

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

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

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

Conclusion: In high-FRS patients, ICP has good short-term outcomes relative to PD without major long-term events related to endocrine and exocrine insufficiency. ICP could be considered as a feasible alternative in selected cases.
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http://dx.doi.org/10.1007/s00423-021-02157-1DOI Listing
May 2021

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

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

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

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

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

Conclusions: The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.
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http://dx.doi.org/10.1186/s12893-020-01004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737276PMC
December 2020

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

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

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

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death, and soon to become the second. There is an urgent need of variables associated to specific pancreatic pathologies to help preoperative differential diagnosis and patient profiling. Pancreatic juice is a relatively unexplored body fluid, which, due to its close proximity to the tumor site, reflects changes in the surrounding tissue. Here we describe in detail the intraoperative collection procedure. Unfortunately, translating pancreatic juice collection to murine models of PDAC, to perform mechanistic studies, is technically very challenging. Tumor interstitial fluid (TIF) is the extracellular fluid, outside blood and plasma, which bathes tumor and stromal cells. Similarly to pancreatic juice, for its property to collect and concentrate molecules that are found diluted in plasma, TIF can be exploited as an indicator of microenvironmental alterations and as a valuable source of disease-associated biomarkers. Since TIF is not readily accessible, various techniques have been proposed for its isolation. We describe here two simple and technically undemanding methods for its isolation: tissue centrifugation and tissue elution.
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http://dx.doi.org/10.3791/61687DOI Listing
November 2020

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

Ann Surg 2020 Nov 9. Epub 2020 Nov 9.

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

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

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

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

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

Conclusion: This pan-European prospective snapshot study found a 5% in-hospital after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000004551DOI Listing
November 2020

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

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

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

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

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

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

Conclusions: It seems to be possible to predict ERp failure after PD. Patients at high risk of failure may benefit more from a specific ERp.
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http://dx.doi.org/10.1007/s00268-020-05693-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527369PMC
November 2020

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

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

Università di Pisa, Pisa, Italy.

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6-10 cases in 38.9% of the centers, 11-20 cases in 16.7%, 21-30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.
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http://dx.doi.org/10.1007/s13304-020-00808-4DOI Listing
June 2020

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

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

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

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1 T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1 CD8 tumor-infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase () gene displayed a decrease in PD-1 cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.
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http://dx.doi.org/10.1158/2326-6066.CIR-19-0403DOI Listing
April 2020

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

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

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

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

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

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

Conclusions: Assessment of preoperative FM at BIVA can improve the accuracy of FRS in predicting CR-POPF following pancreatoduodenectomy.
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http://dx.doi.org/10.1016/j.pan.2020.01.008DOI Listing
April 2020

Trans-duodenal ampullectomy for ampullary neoplasms: early and long-term outcomes in 36 consecutive patients.

Surg Endosc 2020 10 23;34(10):4358-4368. Epub 2019 Oct 23.

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

Background: Trans-duodenal ampullectomy (TDA) is a surgical option for the treatment of selected ampullary neoplasms. The aim of this study was to evaluate our experience with TDA for the treatment of ampullary neoplasms, focusing on indications, technical aspects, and short- and long-term outcomes.

Methods: All TDAs for ampullary neoplasms performed between January 2010 and December 2018 at our institution were retrospectively evaluated. Patients had ampullary neoplasms with low-grade dysplasia or in situ carcinoma (Tis) not suitable for an endoscopic approach, ampullary carcinoma unfit for pancreaticoduodenectomy (PD), or ampullary neuroendocrine G1-tumours.

Results: Thirty-six patients were included in the study: 9 (25.0%) with neoplasms with low-grade dysplasia, 4 (11.1%) with G1 neuroendocrine tumours and 23 (63.9%) with Tis or invasive carcinoma. Mean operative time was 252.5 min. Overall and severe (Clavien-Dindo > IIIa) morbidity rate was 44.4% and 13.9%, respectively. No 90-day mortality was observed. At follow-up, no deaths were observed and local recurrence rate was 11.1% for patients with ampullary adenomas with low-grade dysplasia. Among four patients with neuroendocrine neoplasms, only one developed recurrence (pulmonary). Tis, T1 and T2 lesions were found in 16 (69.6%), 2 (8.7%) and 5 (21.7%) patients, respectively: recurrence occurred in 3 patients with Tis lesions (one malignant), no patients with T1 neoplasms and 2 patients with T2 lesions (3 patients had a survival of > 3 years).

Conclusions: TDA is a feasible and effective surgical procedure for the treatment of ampullary adenomas with low-grade dysplasia when endoscopic approach is contraindicated or has failed. For lesions with evidence of malignancy, TDA seems to be an oncological safe procedure for Tis ampullary cancer and a good palliative procedure for patients unfit for PD. Moreover, TDA may be appropriate for the treatment of G1 ampullary neuroendocrine neoplasms. A large multicentre study of TDA for early ampullary cancers is needed.
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http://dx.doi.org/10.1007/s00464-019-07206-xDOI Listing
October 2020

Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis.

Ann Surg 2019 11;270(5):923-929

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Objective: To evaluate whether perioperative bioimpedance vector analysis (BIVA) predicts the occurrence of surgery-related morbidity.

Summary Background Data: BIVA is a reliable tool to assess hydration status and compartimentalized fluid distribution.

Methods: The BIVA of patients undergoing resection for pancreatic malignancies was prospectively measured on the day prior to surgery and on postoperative day (POD)1. Postoperative morbidity was scored per the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI).

Results: Out of 249 patients, the overall and major complication rates were 61% and 16.5% respectively. The median CCI was 24 (IQR 0.0-24.2), and 24 patients (9.6%) had a complication burden with CCI≥40. At baseline the impedance vectors of severe complicated patients were shorter compared to the vectors of uncomplicated patients only for the female subgroup (P=0.016). The preoperative extracellular water (ECW) was significantly higher in patients who experienced severe morbidity according to the CDC or not [19.4L (17.5-22.0) vs. 18.2L (15.6-20.6), P=0.009, respectively] and CCI≥40, or not [20.3L (18.5-22.7) vs. 18.3L (15.6-20.6), P=0.002, respectively]. The hydration index on POD1 was significantly higher in patients who experienced major complications than in uncomplicated patients (P=0.020 and P=0.025 for CDC and CCI, respectively).At a linear regression model, age (β=0.14, P=0.035), sex female (β=0.40, P<0.001), BMI (β=0.30, P<0.001), and malnutrition (β=0.14, P=0.037) were independent predictors of postoperative ECW.

Conclusion: The amount of extracellular fluid accumulation predicts major morbidity after pancreatic surgery. Female, obese and malnourished patients were at high risk of extracellular fluid accumulation.
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http://dx.doi.org/10.1097/SLA.0000000000003536DOI Listing
November 2019

Thrombosis of the dorsal vein of the penis as first clinical presentation of pancreatic cancer metastatic to the penis.

Tumori 2019 Dec 9;105(6):NP43-NP47. Epub 2019 May 9.

Pancreatic Surgery Unit, Hospital Health Direction, Humanitas Research Hospital, Rozzano (MI), Italy.

Introduction: Though metastatic disease is a common presentation of pancreatic adenocarcinoma, localization to the penis is an extremely rare event despite its abundant vascularization. Primary cancers responsible for penile metastases usually occur in prostate and rectum and are often associated with disseminated malignancy and poor prognosis.

Case Description: A 66-year-old man was diagnosed with adenocarcinoma of the tail of the pancreas after the onset of thrombosis of the dorsal vein of the penis; pubis ultrasound and total body computed tomography scan were negative for metastases at other sites. The patient was submitted to distal pancreatectomy with splenectomy for a pT3 N1 G4 pancreatic ductal adenocarcinoma. Three weeks after discharge, the patient returned to the outpatient clinic complaining of a painful permanent turgidity of the penis shaft. Ultrasound revealed a complete replacement of the cavernosal bodies by multiple nodular masses and a penile biopsy confirmed metastases from the primary pancreatic cancer. The patient started chemotherapy with NAB-paclitaxel and gemcitabine, with excellent control of symptoms. However, the disease progressed to bone and liver and the patient died 9 months after surgery.

Conclusions: Penile localization is an extremely rare event and a standard of care has not been elaborated. Treatments are palliative and mainly aimed at pain relief and can comprise chemotherapy, radiotherapy, and surgery. Identification of venous thrombosis as an early sign of involvement could potentially offer patients an earlier diagnosis and a better treatment option.
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http://dx.doi.org/10.1177/0300891619849273DOI Listing
December 2019

Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification.

Dig Dis 2019 21;37(4):325-333. Epub 2019 Mar 21.

Humanitas Clinical and Research Center, IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Milan, Italy.

Background: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour.

Objectives: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center.

Methods: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading.

Results: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%.

Conclusion: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.
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http://dx.doi.org/10.1159/000499172DOI Listing
May 2019

The evolution of post-operative pancreatic fistula (POPF) classification: A single-center experience.

Pancreatology 2019 Apr 14;19(3):449-455. Epub 2019 Mar 14.

Pancreatic Surgery Unit, Humanitas Research Hospital and University, Rozzano, Milan, Italy.

Background: The ISGPS classification of post-operative pancreatic fistula (POPF) was recently revised, introducing the concept of biochemical leak (BL) which replaced grade A POPF. More recently, an additional distinction on three different subclasses for grade B (B1-B3) POPF was proposed. The aim of this study was to evaluate the impact of these modifications in clinical practice.

Methods: All pancreatico-duodenectomies (PD) and distal pancreatectomies (DP) performed between 2010 and 2016 were retrospectively evaluated. Incidence and grade of POPF using the old and new ISGPS classification were evaluated. Three grade B subclasses (B1: maintenance of abdominal drain >3 weeks; B2: adoption of specific medical treatments for POPF; B3: use of radiological procedures) were evaluated for clinical severity.

Results: A total of 716 patients (502 PD, 214 DP) were evaluated. The new ISGPS classification reduced the reported rate of POPF (30.7% vs 35.2% for PD, p > 0.05; 28% vs 44.9% for DP, p < 0.05), due to the abolition of grade A POPF. Grade B1, B2 and B3 rates were 3.1%, 73.8% and 23.1% in PD and 12.3%, 47.4% and 40.3% in DP, respectively. Passing from B1 to B3, significant increases in wound infection (0-40%), mean length of stay in PD (14.7-22.5 days; p < 0.05) and readmission rate in DP (0-39.1%) were observed.

Conclusions: The new ISGPS classification significantly reduces the reported rate of POPF, particularly after DP. The three different grade B subclasses (B1-B3) better discriminate the severity of post-operative course, especially after PD.
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http://dx.doi.org/10.1016/j.pan.2019.03.004DOI Listing
April 2019

Long-Term Active Surveillance of Screening Detected Subsolid Nodules is a Safe Strategy to Reduce Overtreatment.

J Thorac Oncol 2018 10 16;13(10):1454-1463. Epub 2018 Jul 16.

Department of Thoracic Surgery, IRCCS Istituto Nazionale Tumori, Milan, Italy.

Introduction: Lung cancer presenting as subsolid nodule (SSN) can show slow growth, hence treating SSN is controversial. Our aim was to determine the long-term outcome of subjects with unresected SSNs in lung cancer screening.

Methods: Since 2005, the Multicenter Italian Lung Detection (MILD) screening trial implemented active surveillance for persistent SSN, as opposed to early resection. Presence of SSNs was related to diagnosis of cancer at the site of SSN, elsewhere in the lung, or in the body. The risk of overall mortality and lung cancer mortality was tested by Cox proportional hazards model.

Results: SSNs were found in 16.9% (389 of 2303) of screenees. During 9.3 ± 1.2 years of follow-up, the hazard ratio of lung cancer diagnosis in subjects with SSN was 6.77 (95% confidence interval: 3.39-13.54), with 73% (22 of 30) of cancers not arising from SSN (median time to diagnosis 52 months from SSN). Lung cancer-specific mortality in subjects with SSN was significantly increased (hazard ratio = 3.80; 95% confidence interval: 1.24-11.65) compared to subjects without lung nodules. Lung cancer arising from SSN did not lead to death within the follow-up period.

Conclusions: Subjects with SSN in the MILD cohort showed a high risk of developing lung cancer elsewhere in the lung, with only a minority of cases arising from SSN, and never representing the cause of death. These results show the safety of active surveillance for conservative management of SSN until signs of solid component growth and the need for prolonged follow-up because of high risk of other cancers.
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http://dx.doi.org/10.1016/j.jtho.2018.06.013DOI Listing
October 2018

Application of minimally invasive pancreatic surgery: an Italian survey.

Updates Surg 2019 Mar 16;71(1):97-103. Epub 2018 May 16.

Humanitas University, Rozzano, MI, Italy.

The value of minimally invasive pancreatic surgery (MIPS) is still debated. To assess the diffusion of MIPS in Italy and identify the barriers preventing wider implementation, a questionnaire was developed under the auspices of three Scientific Societies (AISP, It-IHPBA, SICE) and was sent to the largest possible number of Italian surgeons also using the mailing list of the two main Italian Surgical Societies (SIC and ACOI). The questionnaire consisted of 25 questions assessing: centre characteristics, facilities and technologies, type of MIPS performed, surgical techniques employed and opinions on the present and future value of MIPS. Only one reply per unit was considered. Fifty-five units answered the questionnaire. While 54 units (98.2%) declared to perform MIPS, the majority of responders were not dedicated to pancreatic surgery. Twenty-five units (45.5%) performed < 20 pancreatic resections/year and 39 (70.9%) < 10 MIPS per year. Forty-nine units (89.1%) performed at least one minimally invasive (MI) distal pancreatectomy (DP), and 10 (18.2%) at least one MI pancreatoduodenectomy (PD). Robotic assistance was used in 18 units (31.7%) (14 DP, 7 PD). The major constraints limiting the diffusion of MIPS were the intrinsic difficulty of the technique and the lack of specific training. The overall value of MIPS was highly rated. Our survey illustrates the current diffusion of MIPS in Italy and underlines the great interest for this approach. Further diffusion of MIPS requires the implementation of standardized protocols of training. Creation of a prospective National Registry should also be considered.
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http://dx.doi.org/10.1007/s13304-018-0535-3DOI Listing
March 2019

Detection of Subsolid Nodules in Lung Cancer Screening: Complementary Sensitivity of Visual Reading and Computer-Aided Diagnosis.

Invest Radiol 2018 08;53(8):441-449

Department of Thoracic Surgery, IRCCS Istituto Nazionale Tumori, Milan, Italy.

Objectives: The aim of this study was to compare computer-aided diagnosis (CAD) and visual reading for the detection of subsolid nodules (SSNs) in volumetrl measuremic low-dose computed tomography (LDCT) for lung cancer screening.

Materials And Methods: Prospective visual detection (VD) and manuaent of SSN were performed in the 2303 baseline volumetric LDCTs of the Multicenter Italian Lung Detection trial. Baseline and 2- and 4-year LDCTs underwent retrospective CAD analysis, subsequently reviewed by 2 experienced thoracic radiologists. The reference standard was defined by the cumulative number of SSNs detected by any reading method between VD and CAD. The number of false-positive CAD marks per scan (FP/scan) was calculated. The positive predictive value of CAD was quantified per nodule (PPV) and per screenee (PPV). The sensitivity and negative predictive value were compared between CAD and VD. The longitudinal 3-time-point sensitivity of CAD was calculated in the subgroup of persistent SSNs seen by VD (ratio between the prevalent SSNs detected by CAD through 3 time points and the total number of persistent prevalent SSNs detected by VD) to test the sensitivity of iterated CAD analysis during a screening program. Semiautomatic characteristics (diameter, volume, and mass; both for whole nodule and solid component) were compared between SSN detected CAD-only or VD-only to investigate whether either reading method could suffer from specific sensitivity weakness related to SSN features. Semiautomatic and manual diameters were compared using Spearman ρ correlation and Bland-Altman plot.

Results: Computer-aided diagnosis and VD detected a total of 194 SSNs in 6.7% (155/2,303) of screenees at baseline LDCT. The CAD showed mean FP/scan of 0.26 (604/2,303); PPV 22.5% (175/779) for any SSN, with 54.4% (37/68) for PSN and 19.4% for NSN (138/711; P < 0.001); PPV 25.6% (137/536). The sensitivity of CAD was superior to that of VD (88.4% and 34.2%, P < 0.001), as well as negative predictive value (99.2% and 95.5%, P < 0.001). The longitudinal 3-time-point sensitivity of CAD was 87.5% (42/48). There was no influence of semiautomatic characteristics on the performance of either reading method. The diameter of the solid component in PSN was larger by CAD compared with manual measurement. At baseline, CAD detected 3 of 4 SSNs, which were first overlooked by VD and subsequently evolved to lung cancer.

Conclusions: Computer-aided diagnosis and VD as concurrent reading methods showed complementary performance, with CAD having a higher sensitivity, especially for PSN, but requiring visual confirmation to reduce false-positive calls. Computer-aided diagnosis and VD should be jointly used for LDCT reading to reduce false-negatives of either lone method. The semiautomatic measurement of solid core showed systematic shift toward a larger diameter, potentially resulting in an up-shift within Lung CT Screening Reporting and Data System classification.
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http://dx.doi.org/10.1097/RLI.0000000000000464DOI Listing
August 2018

Impact of Sarcopenic Obesity on Failure to Rescue from Major Complications Following Pancreaticoduodenectomy for Cancer: Results from a Multicenter Study.

Ann Surg Oncol 2018 Jan 7;25(1):308-317. Epub 2017 Nov 7.

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

Background: Failure to rescue (FTR) is a quality-of-care indicator in pancreatic surgery, but may also identify patients who may not tolerate major postoperative complications despite being treated with best available care. Previous studies found that high visceral adipose tissue-to-skeletal muscle ratio is associated with poor outcomes following pancreaticoduodenectomy (PD). The aim of the study is to assess the impact of sarcopenic obesity on occurrence of FTR from major complications in cancer patients undergoing PD.

Methods: Prospectively collected data from three high-volume hospitals were reviewed. Total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed at preoperative staging computed tomography scan. Sarcopenic obesity was defined as high VFA/TAMA ratio. FTR was defined as postoperative mortality following major complication.

Results: 120 patients with major complications were included. FTR occurred in 23 (19.2%) patients. The "seminal" complications leading to FTR were pancreatic or biliary fistula-related sepsis (n = 14), postoperative pancreatic fistula (POPF)-related hemorrhage (n = 5), and duodenojejunal anastomosis leak-related sepsis (n = 1). On univariate analysis, older age [odds ratio (OR) 3.5, p = 0.034], American Society of Anesthesiologists (ASA) score 3+ (OR 4.2, p = 0.005), cardiovascular disease (OR 3.3, p = 0.013), low serum albumin (OR 2.6, p = 0.042), sarcopenic obesity (OR 4.2, p = 0.009), POPF (OR 3.1, p = 0.027), and cardiorespiratory complications (OR 3.7, p = 0.011) were significantly associated with FTR. On multivariate analysis, sarcopenic obesity [OR 5.7, 95% confidence interval (CI) 1.6-20.7, p = 0.008], ASA score 3+ (OR 4.1, 95% CI 1.2-14.3, p = 0.025), and pancreatic fistula (OR 3.2, 95% CI 1.0-10.2, p = 0.045) were independently associated with FTR.

Conclusion: Sarcopenic obesity, low preoperative physical status, and occurrence of pancreatic fistula are associated with significantly higher risk of FTR from major complications after PD.
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http://dx.doi.org/10.1245/s10434-017-6216-5DOI Listing
January 2018

Consequences of Increases in Antibiotic Resistance Pattern on Outcome of Pancreatic Resection for Cancer.

J Gastrointest Surg 2017 Oct 5;21(10):1650-1657. Epub 2017 Jul 5.

Pancreatic Surgery Unit, Department of Surgery, Humanitas Research Hospital, Rozzano, Milan, Italy.

Background: The role of drug-resistance infections on surgical outcomes is controversial. The aim of the study was to determine whether increase antibiotic resistance was an independent risk factor for development of major non-infectious postoperative complications.

Methods: This work included a multicenter cohort study of patients who underwent pancreatic resections for cancer over a 3-year interval. The primary outcome was major non-infectious complication rate developing after the occurrence of multi-drug sensitive (MDS) infection, multi-drug-resistant infection (MDR), and extensive drug-resistant (XDR) infection. Multivariate logistic regression models were used to adjust for patient and operative effects.

Results: Eligible patients (517) were selected for the analysis. One hundred and thirteen (21.8%) patients had major non-infectious complications with a rate of 12.9% in the no infection group, 29.3% in the MSD, 41.5% in the MDR, and 58.8% in the XDR (p < 0.001). The median time of infection occurrence was postoperative days 4 (2-7 IQR) and 7 (3-12 IQR) non-infectious complications. At multivariate analysis, the risk of having major non-infectious complications was 2.67 (95% CI 1.24-5.77, P = 0.012) for MDR, 5.04 (95% CI 2.35-10.80, P < 0.001) for MDR, and 9.64 (95% CI 2.71-34.28, P < 0.001) for XDR.

Conclusion: Antimicrobial resistance is significantly associated with the risk of major non-infectious morbidity.
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http://dx.doi.org/10.1007/s11605-017-3483-1DOI Listing
October 2017

Salvage Islet Auto Transplantation After Relaparatomy.

Transplantation 2017 10;101(10):2492-2500

1 Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2 Diabetes Research Institute; IRCCS San Raffaele Scientific Institute, Milan, Italy. 3 Clinical Transplant Unit, Division of Immunology, Transplantation and Infectious Diseases; IRCCS San Raffaele Scientific Institute, Milan, Italy. 4 Humanitas Clinical and Research Center, Pancreatic Surgery, Rozzano, Italy. 5 Humanitas Clinical and Research Center, Diabetology, Rozzano, Italy. 6 Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. 7 Vita-Salute San Raffaele University, Milan, Italy. 8 Humanitas University, Department of Biomedical Sciences, Rozzano, Italy.

Background: To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery.

Methods: From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy.

Results: The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT.

Conclusions: Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.
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http://dx.doi.org/10.1097/TP.0000000000001750DOI Listing
October 2017

Management and Outcomes of Pancreatic Resections Performed in High-Volume Referral and Low-Volume Community Hospitals Lead by Surgeons Who Shared the Same Mentor: The Importance of Training.

Dig Surg 2018 10;35(1):42-48. Epub 2017 Mar 10.

Ospedale San Carlo Borromeo, Milano, Italy.

Background: High hospital volume improves outcomes after pancreatic resection. The aim of this study was to assess if practice and outcomes differed between high- and low-volume centers across which chief surgeons shared a similar training and mentoring.

Methods: Data on patients undergoing standard pancreatic resections (2010-2013) at 7 Italian hospitals were collected. Chiefs of pancreatic surgery at each hospital had received the same training, with the same mentor. Two centers were high-volume referral hospitals for pancreatic disease, while 5 were low-volume hospitals.

Results: A total of 856 patients were included, with median annual volume of resections 82 at high-volume referral hospitals and 11 at low-volume hospitals. Patients at low-volume hospitals were older, had more comorbidities, and were more often referred from the emergency room. Intraoperative techniques and reconstruction methods were similar. Comparable rates of major postoperative complications (18 vs. 22%; p = 0.236) and pancreatic fistula (29 vs. 32%; p = 0.287) were achieved in both groups, with no significant increases in failure to rescue from grade B-C fistula (6.2 vs. 15.0%; p = 0.108) and mortality (2.4 vs. 4.1%; p = 0.233) in low-volume hospitals. Postoperative length of stay was shorter in high-volume referral hospitals (10 vs. 15 days; p < 0.001).

Conclusion: Similar postoperative outcomes can be achieved across high- and low-volume centers where chief surgeons shared a similar training and mentoring. However, multidisciplinary postoperative provision more often associated with high-volume centers may also affect outcomes.
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http://dx.doi.org/10.1159/000464412DOI Listing
August 2018

Enhanced recovery pathway in patients undergoing distal pancreatectomy: a case-matched study.

HPB (Oxford) 2017 03 30;19(3):270-278. Epub 2016 Nov 30.

Department of Surgery, Vita-Salute University, San Raffaele Hospital, Milan, Italy. Electronic address:

Background: Enhanced recovery (ER) pathways have improved outcomes across multiple surgical specialties, but reports concerning their application in distal pancreatectomy (DP) are lacking. The aim of this study was to assess compliance with an ER protocol and its impact on short-term outcomes in patients undergoing DP.

Methods: Prospectively collected data were reviewed. One hundred consecutive patients undergoing DP were treated within an ER pathway comprising 18 care elements. Each patient was matched 1:1 with a patient treated with usual perioperative care. Match criteria were age, BMI, ASA score, lesion site, and type of disease.

Results: Adherence to ER items ranged from 15% for intraoperative restrictive fluids to 100% for intraoperative warming, antibiotic and anti-thrombotic prophylaxis. Patients in ER group experienced earlier recovery of gastrointestinal function (2 vs. 3 days, p < 0.001), oral intake (2 vs. 4 days, p < 0.001), and suspension of intravenous infusions (3 vs. 5 days, p < 0.001). Overall morbidity was similar in the two groups (72% vs. 78%). Length of hospital stay (LOS) was reduced in ER patients without postoperative complications (6.7 ± 1.2 vs. 7.6 ± 1.6 days, p = 0.041).

Conclusions: An ER pathway for DP yielded an earlier postoperative recovery and shortened LOS in uneventful patients. Postoperative morbidity and readmissions were similar in both groups.
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http://dx.doi.org/10.1016/j.hpb.2016.10.014DOI Listing
March 2017

Gallstone ileus: literature review.

Acta Biomed 2016 07 28;87 Suppl 3:40-4. Epub 2016 Jul 28.

Department of Surgical Sciences, Section of Radiological Sciences, University of Parma, Parma Hospital, Parma, Italy.

Gallstone ileus is a rare case of mechanical intestinal obstruction observed in patients with history of cholelithiasis or cholecystitis. Its diagnosis is difficult and it is characterized by high mortality rate. Diagnostic Imaging plays an important role in the management of patients with suspected gallstone ileus because an early diagnosis could reduce the mortality. Abdominal Computed Tomography (CT) is the preferred modality because of its rapid diagnosis. Surgery remains the gold standard treatment.
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July 2016

Defecography: a still needful exam for evaluation of pelvic floor diseases.

Acta Biomed 2016 07 28;87 Suppl 3:34-9. Epub 2016 Jul 28.

Department of Surgical Sciences, Section of Radiological Sciences, University of Parma, Parma Hospital, Parma, Italy.

The aim of this discussion is to describe what is a defecography, how we have to perform it, what can we see and to present the main physio-pathological illnesses of pelvic floor and anorectal region that can be studied with this method and its advantages over other screening techniques. Defecography is a contrastographic radiological examination that highlights structural and functional pelvic floor diseases. Upon preliminary ileum-colic opacification giving to patient radiopaque contrast, are first acquired static images (at rest, in maximum voluntary contraction of the pelvic muscles, while straining) and secondarily dynamic sequences (during evacuation), allowing a complete evaluation of the functionality of the anorectal region and the pelvic floor. Defecography is an easy procedure to perform widely available, and economic, carried out in conditions where the patient experiences symptoms, the most realistic possible. It can be still considered reliable technology and first choice in many patients in whom the clinic alone is not sufficient and it is not possible or necessary to perform a study with MRI.
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July 2016

MRI findings of intraductal papillary mucinous neoplasms (IPMNs).

Acta Biomed 2016 07 28;87 Suppl 3:28-33. Epub 2016 Jul 28.

Department of Surgical Sciences, Section of Radiological Sciences, University of Parma, Parma Hospital, Parma, Italy.

Cystic lesions of the pancreas are relatively frequent imaging findings due to the improvement of imaging technologies. They may be secondary to both benign and malignant disease processes and their prevalence increases with age. In most cases, these lesions are detected incidentally by computed tomography and magnetic resonance imaging (MRI) performed for other reasons. Intraductal papillary mucinous neoplasms (IPMNs) represent 25% of the cystic neoplasms, morphologically classified into "main pancreatic duct IPMN" (MPD-IPMN), "side branches IPMN" (SB-IPMN) and mixed forms. Magnetic Resonance Cholangiopancreatography (MRCP) is a multiparametricity not invasive radiological technique that doesn't use ionizing radiation or organ iodinized contrast agents; it allows an accurate characterization of the lesions (number and size of cystic lesions, internal features of a cyst, ducts dilation, communication with main pancreatic duct) that is important to guide the differential diagnosis and establish a correct follow-up. International guidelines consider IPMN of MPD and mixed forms to be an indication for surgery, while clinical and radiological follow-up is indicated in asymptomatic patients with SB-IPMN, especially when lesions are < 2,5-3 cm in diameter and there are no mural nodules or dilation of MPD.
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July 2016

Overuse of surgery in patients with pancreatic cancer. A nationwide analysis in Italy.

HPB (Oxford) 2016 05 5;18(5):470-8. Epub 2016 Feb 5.

Italian Association for the Study of Pancreas (AISP), Italy; Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy.

Background: According to current guidelines, pancreatic cancer patients should be strictly selected for surgery, either palliative or resective.

Methods: Population-based study, including all patients undergoing surgery for pancreatic cancer in Italy between 2010 and 2012. Hospitals were divided into five volume groups (quintiles), to search for differences among volume categories.

Results: There were 544 hospitals performing 10 936 pancreatic cancer operations. The probability of undergoing palliative/explorative surgery was inversely related to volume, being 24.4% in very high-volume hospitals and 62.5% in very low-volume centres (adjusted OR 5.175). Contrarily, the resection rate in patients without metastases decreased from 86.9% to 46.1% (adjusted OR 7.429). As for resections, the mortality of non-resective surgery was inversely related to volume (p < 0.001). Surprisingly, mortality of non-resective surgery was higher than that for resections (8.2% vs. 6.7%; p < 0.01). Approximately 9% of all resections were performed on patients with distant metastases, irrespective of hospital volume group. The excess cost for the National Health System from surgery overuse was estimated at 12.5 million euro.

Discussion: Discrepancies between guidelines on pancreatic cancer treatment and surgical practice were observed. An overuse of surgery was detected, with serious clinical and economic consequences.
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http://dx.doi.org/10.1016/j.hpb.2015.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857063PMC
May 2016
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