[Show abstract][Hide abstract] ABSTRACT: Islet volume and endocrine pancreas architecture (islet size distribution) may be independent determinants of beta cell function. Furthermore, the accuracy of HOMA indexes in predicting β-cell mass has never been assessed. Here, we investigated the relationships between islet volume, islet density and islet size distribution, estimated after pancreatic tissue digestion, with established indexes of β-cell function in humans. We included in this study 42 patients who were candidates for islet autotransplantation and had well-characterized glucose metabolism. Indexes of insulin secretion were calculated and compared with the islet volume, as a surrogate of β-cell mass, obtained after digestion of pancreas. Islet counting analysis showed considerable interindividual variation in islet density and size. Islet volume, but not density nor size, was the only independent determinant of β-cell function assessed by insulin HOMA β-cell. Islet volume was significantly reduced in the patients with overt hyperglycemia, but not in patients with impaired fasting glucose. Insulin HOMA β-cell predicted islet volume better than other measures of fasting insulin secretion. In conclusion, the present study documented a close direct relationship between indexes of β-cell function and islet volume in humans. The insulin HOMA β-cell provides a more reliable estimate of pancreatic islet volume than fasting glucose before islet isolation.
[Show abstract][Hide abstract] ABSTRACT: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality.
Retrospective multinational study including SCN diagnosed between 1990 and 2014.
2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).
After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Gut 06/2015; DOI:10.1136/gutjnl-2015-309638 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the developed world, pancreatic surgery is becoming more common, with an increasing number of patients developing diabetes because of either partial or total pancreatectomy, with a significant impact on quality of life and survival. Although these patients are expected to consume increasing health care resources in the near future, many aspects of diabetes after pancreatectomy are still not well defined. The treatment of diabetes in these patients takes advantage of the therapies used in type 1 and 2 diabetes; however, no specific guidelines for its management, both immediately after pancreatic surgery or in the long term, have been developed. In this article, on the basis of both the literature and our clinical experience, we address the open issues and discuss the most appropriate therapeutic options for patients with diabetes after pancreatectomy.
Current Diabetes Reports 04/2015; 15(4):589. DOI:10.1007/s11892-015-0589-2 · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: No data are available about distal pancreatectomy (DP) in Italy, regarding variability of care among centers, and outcome of minimally invasive distal pancreatectomy (MIDP) in a multicenter setting. Hence, a survey was conducted among 20 institutions experienced in pancreatic surgery by the Italian Association for Study of Pancreas. Centers were asked to fill in two questionnaires about (1) general approach and perioperative protocols for DP and MIDP; (2) detailed operative results of MIDP in the period 2010-2011. Results of questionnaire 1: a great variability in perioperative approach was observed: octreotide was used in 50 % of centers, enzyme supplementation in 35 %, postoperative gastric suction in 80 % and oral liquids on day 1 in 55 %. All hospitals used at least one drain and its removal ranged between days 3-5 (in absence of fistula). Differences in type and timing of post-splenectomy vaccinations were recorded. As regards MIDP, 17/20 centers performed laparoscopic or robotic DP. MIDP rate on overall DP varied among centers (range 0-82 %) and it doubled from 2007 (14 %) to 2011 (28 %). Results of questionnaire 2: in the period 2010-2011, 171 MIDP were performed (140 laparoscopic, 31 robotic). Overall conversion rate was 17 %, mean operative time was 230 min and blood loss 285 ml. Mortality was nil and morbidity was 62 %, with 4 % relaparotomies. Pancreatic fistula occurred in 49 % (grade A 35 %, B 14 %). Mean postoperative stay was 9.8 days with 10 % readmission rate. The results indicated a great variability in DP management among Italian centers. Most centers performed MIDP, but MIDP rate on overall DP largely varied among centers. As regards MIDP conversion rate and hospital stay were found to be worse than those in single-institution series.
Updates in Surgery 11/2014; 66(4). DOI:10.1007/s13304-014-0273-0
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45 %) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8 %, p = 0.038). CTCs were found in 45 % of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.
[Show abstract][Hide abstract] ABSTRACT: Background:
Laparoscopic distal pancreatectomy (LDP) has been recently proposed as the procedure of choice for lesions of the pancreatic body and tail in experienced centres. The purpose of this study is to assess the potential advantages of LDP in a consecutive series of 100 patients.
Propensity score matching was used to identify patients for comparison between LDP and control open group. Match criteria were: age, gender, ASA score, BMI, lesion site and size, and malignancy. All patients were treated according to an early feeding recovery policy. Primary endpoint was postoperative morbidity rate. Secondary endpoints were operative time, blood transfusion, length of hospital stay (LOS), hospital costs, and quality of life.
Thirty patients of the LDP group had pancreatic adenocarcinoma. Conversion to open surgery was necessary in 23 patients. Mean operative time was 29 min shorter in the open group (p = 0.002). No significant difference between groups was found in blood transfusion rate and postoperative morbidity rate. LDP was associated with an early postoperative rehabilitation and a shorter LOS in uneventful patients. Economic analysis showed 775 extra cost per patient of the LDP group. General health perception and vitality were better in the LDP group one month after surgery.
Laparoscopic distal pancreatectomy improved short-term postoperative recovery and quality of life in a consecutive series of both cancer and non-cancer patients. Despite the extra cost, the laparoscopic approach should be considered the first option in patients undergoing distal pancreatectomy.
[Show abstract][Hide abstract] ABSTRACT: Autologous islet cell transplantation is a procedure performed to prevent or reduce the severity of diabetes after pancreatic resection. Autologous islet cell transplantation is being used almost exclusively in patients undergoing pancreatectomy because of painful, chronic pancreatitis, or multiple recurrent episodes of pancreatitis that is not controlled by standard medical and surgical treatments. Here, we discuss the possibility of extending the clinical indications for this treatment on the basis of our experience in patients undergoing pancreatic surgery for both nonmalignant and malignant diseases, including patients undergoing completion pancreatectomy because of anastomosis leakage after pancreaticoduodenectomy and those with pancreatic anastomosis deemed at high risk for failure.
Current Diabetes Reports 08/2014; 14(8):512. DOI:10.1007/s11892-014-0512-2 · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To characterize the clinical signature and etiopathogenetic factors of diabetes associated with pancreas disease [type 3 diabetes mellitus (T3cDM)]. To estimate incidence and identify predictors of both diabetes onset and remission after pancreatic surgery. A prospective observational study was conducted. From January 2008 to December 2012, patients (n = 651) with new diagnosis of pancreatic disease admitted to the Pancreatic Surgery Unit of the San Raffaele Scientific Institute were evaluated. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. At baseline, the prevalence of diabetes was 38 % (age of onset 64 ± 11 years). In most cases, diabetes occurred within 48 months from pancreatic disease diagnosis. Among different pancreatic diseases, minor differences were observed in diabetes characteristics, with the exception of the prevalence. Diabetes appeared associated with classical risk factors for type 2 diabetes (i.e., age, sex, family history of diabetes and body mass index), and both beta-cell dysfunction and insulin resistance appeared relevant determinants. The prevalence of adult-onset autoimmune diabetes was as previously reported within type 2 diabetes. Within a few days after surgery, either diabetes remission or new-onset diabetes was observed. In patients with pancreatic cancer, no difference in diabetes remission was observed after palliative or resective surgery. Classical risk factors for type 2 diabetes were associated with the onset of diabetes after surgery. T3cDM appeared as a heterogeneous entity strongly overlapped with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Background
Enhanced recovery after surgery (ERAS®) pathways have reduced morbidity and length of hospital stay (LOS) in orthopedics, bariatric, and colorectal surgery. New perioperative care protocols have been tested in patients undergoing pancreaticoduodenectomy (PD), with controversial results on morbidity. Incomplete data about ERAS items compliance have been reported. The aim of this study was to assess compliance with an ERAS protocol and its impact on short-term outcome in patients undergoing PD.
A comprehensive ERAS protocol was applied in 115 consecutive patients undergoing PD. Each ERAS patient was matched with one patient who received standard perioperative care. Match criteria were age, gender, malignant/benign disease, and PD-specific prognostic score.
No adverse effect related to ERAS items occurred. Compliance with postoperative items ranged between 38 and 66 %. The ERAS group had an earlier recovery of mobilization (p
World Journal of Surgery 05/2014; 38(11). DOI:10.1007/s00268-014-2653-5 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety and feasibility of laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with autologous islet transplantation (AIT) for benign tumors of the pancreatic body-neck.
Three non-diabetic, female patients (age 37, 44 and 35 years, respectively) were declared candidates for surgery, between May and September 2011, because of pancreatic body/neck cystic lesions. The planned operation was an LSPDP associated with AIT from the normal pancreas distal to the neoplasm. Islets isolation was performed on the residual pancreatic parenchyma after frozen section examination of the margin. Purified autologous islets were infused into the portal vein by a percutaneous transhepatic approach the day after surgery.
The procedure was performed successfully in all the three cases, and the spleen was preserved along with its vessels. Mean operation time was 283 ± 52 min and average blood loss was 133 ± 57 mL. Residual pancreas weights were 33, 22 and 30 g, and 105.200, 40.390 and 94.790 islet equivalents were isolated, respectively. Surgical complications occurred in one patient (grade A pancreatic fistula). Postoperative stays were 6, 6 and 7 d, respectively. Histopathological evaluation revealed mucinous cystic neoplasm in cases 1 and 3, and serous cystic neoplasm in patient 2. No postoperative insulin administration was required. One patient developed a transient partial portal thrombosis 2 mo after islet infusion. Patients are insulin independent at a mean follow up of 8 ± 2 mo.
Combination of LSPDP and AIT is feasible and could be effective to minimize the surgical impact for benign neoplasm of pancreatic body-neck.
World Journal of Gastroenterology 04/2014; 20(14):4030-6. DOI:10.3748/wjg.v20.i14.4030 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
Percutaneous islet allo-transplantation, needing immunosuppression, is a traditional less invasive alternative to surgical pancreas transplantation for brittle type-1 diabetes, while PIPIAT, not needing immunosuppression, is usually performed after pancreatic surgery for chronic pancreatitis to prevent diabetes. Our aim was to assess feasibility, technical aspects, complications and clinical outcome of PIPIAT following pancreatic surgery, not only for chronic pancreatitis but also for benign and malignant nodules.
METHOD AND MATERIALS
From 2008 to 2012, 41 patients were enrolled for PIPIAT 24/48 hours after pancreatic surgery (total pancreatectomy, distal pancreatectomy for benign/borderline neoplasms of pancreatic body-neck). PIPIAT was performed using a combined US and fluoroscopy-guided technique (4-F catheter): portography and portal vein pressure assessment were performed before and after islet transplantation. Intrahepatic tract embolization was performed before final catheter removal. PIPIAT feasibility, complications, median-follow-up, metabolic (insulin independence rate, graft function based on β-score, marker of islet function ) and oncologic (malignant and metastatic diseases) outcomes were recorded.
PIPIAT wasn’t performed in 7/41 patients (4 for inadequate islet mass, 2 for hemodynamic instability, 1 for islet culture contamination), while it was successfully performed in 34/34 patients. PIPIAT-related complications occurred in 8 patients (23.5%): 4 bleedings (2 requiring transfusions), 3 portal thromboses (1 complete, 2 partial), 1 sepsis. Median follow-up duration was 546 days. Insulin independence was achieved in 15/34 patients (44%), partial graft function in 16/34 patients (47%), no function in 3/34 patients (6%). Seventeen patients had malignancy; none of them developed liver metastases during follow-up.
PIPIAT, performed under a combined US and fluoroscopy guidance and not requiring immunosuppression, is feasible, with a relatively low complication rate and a better metabolic outcome than allo-transplantation.
PIPIAT indications can be extended to selected patients with neoplasm, both benign and malignant. An increased islet mass may lead to the improvement of the metabolic outcome.
Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
Despite the improvement in technique/expertise, pancreatic surgery remains burdened with a high complication rate. Our aim was to report our 10-year single-centre experience about the clinical relevance and the interventional-radiological management of the postoperative complications (treatment/prevention) on 1292 patients submitted to pancreatic surgery.
METHOD AND MATERIALS
In 2000-2012, 1292 patients were submitted to pancreatic surgery (total pancreatectomy, duodeno-cephalo-pancreatectomy, distal pancreatectomy). Patients were classified on the basis of the complication severity in 5 classes (Clavien-Dindo classification): 0=none, class1-2=conservative treatment, 3a=endoscopic/radiological interventional, 3b=surgery, 4=intensive care, 5=death. Interventional-radiological management consisted of: PTC/biliary drainage in case of biliary fistula (bile in surgical drainage, normal bilirubin levels/undilated biliary ducts at US) under US/fluoroscopic guidance (right approach, puncturing along the course of the sixth-segment portal branch (Chiba needle 21G), or left approach if aerobilia/adequate volume of left hepatic lobe); embolization (microcoils/PVA-particles) or covered-stenting (Viabahn-Gore) in case of bleeding; percutaneous drainage (US/CT-guidance) in case of liquid/infected collection. Percutaneous intra-portal islet auto-transplantation (PIPIAT) was performed in case of total pancreatectomy to prevent diabetes.
Patients were classified as follows: 524/1292 (40%) class 0; 210/1292 (16%) class 1; 361/1292 (28%) class 2; 79/1292 (6%) class 3a; 55/1292 (4%) class 3b; 24/1292 (2%) class 4; 39/1292 (3%) class 5. Among the 79 class-3a-patients, 74/79 required radiological-interventional management, 5/79 endoscopic management. The 74 interventional procedures were the following: 32 drainages of liquid/fluid infected collections, 30 biliary drainages, 12 bleeding management (9/12 embolization; 3/12 covered-stenting). 25/1292 underwent PIPIAT.
In centres of excellence pancreatic surgery has a low rate of complications, usually successfully managed and prevented by interventional-radiological procedures. In particular PIPIAT is an advanced, non invasive technique in the prevention of postsurgical diabetes.
In centres of excellence, interventional-radiological procedures take part in the management/prevention of the complications of pancreatic surgery, reducing the morbidity/mortality.
Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
[Show abstract][Hide abstract] ABSTRACT: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma.
Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion.
From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation.
A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.
International journal of radiation oncology, biology, physics 12/2013; 87(5):1000-1006. DOI:10.1016/j.ijrobp.2013.09.012 · 4.26 Impact Factor