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Elisa Giovannetti,
Arjan van der Velde,
Niccola Funel,
Enrico Vasile,
Vittorio Perrone,
Leticia G Leon, Nelide De Lio,
Amir Avan,
Sara Caponi,
Luca E Pollina,
Valentina Gallá,
Hiroko Sudo,
Alfredo Falcone,
Daniela Campani,
Ugo Boggi,
Godefridus J Peters
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ABSTRACT: Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients.
High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDACs clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome.
Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.
PLoS ONE 11/2012; 7(11):e49145. · 4.09 Impact Factor
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Pancreatology 09/2012; 12(5):421-2. · 1.99 Impact Factor
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Ugo Boggi,
Fabio Vistoli,
Francesca Maria Egidi,
Piero Marchetti, Nelide De Lio,
Vittorio Perrone,
Fabio Caniglia,
Stefano Signori,
Massimiliano Barsotti,
Matteo Bernini,
Margherita Occhipinti,
Daniele Focosi,
Gabriella Amorese
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ABSTRACT: Pancreas transplantation consistently induces insulin-independence in beta-cell-penic diabetic patients, but at the cost of major surgery and life-long immunosuppression. One year after grafting, patient survival rate now exceeds 95 % across recipient categories, while insulin independence is maintained in some 85 % of simultaneous pancreas and kidney recipients and in nearly 80 % of solitary pancreas transplant recipients. The half-life of the pancreas graft currently averages 16.7 years, being the longest among extrarenal grafts, and substantially matching the one of renal grafts from deceased donors. The difference between expected (100 %) and actual insulin-independence rate is mostly explained by technical failure in the postoperative phase, and rejection in the long-term period. Death with a functioning graft remains a further major issue, especially in uremic patients who have undergone prolonged periods of dialysis. Refinements in graft preservation, surgical techniques, immunosuppression, and prophylactic treatments are expected to further improve the results of pancreas transplantation.
Current Diabetes Reports 07/2012; 12(5):568-79. · 2.50 Impact Factor
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International Journal of Colorectal Disease 06/2012; · 2.38 Impact Factor
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ABSTRACT: Pancreatic fistula (PF) occurs frequently after central pancreatectomy (CP), but it is not clear from which pancreatic stump it arises and, consequently, which interventions can reduce its incidence and severity. The information could be obtained if the two pancreatic remnants were segregated into different body compartments.
In eight consecutive patients, the cut end of the distal pancreatic stump after CP was brought in the inframesocolic compartment through a small defect created in the transverse mesocolon. Pancreatojejunostomy was hence constructed in the intraperitoneal compartment, being divided by the retroperitoneal right-sided pancreatic stump by the transverse mesocolon itself. Five patients were operated on open, and three by robot-assisted laparoscopy. PF was defined according to the criteria proposed by the International Study Group on Pancreatic Fistula.
PF fistula developed in five out eight patients (three grade A and two grade B). Amylase concentration in the fluid obtained from surgical drains showed that the two pancreatic remnants were actually segregated into different body compartments and that four out of five PF originated from the right remnant. Mean hospital stay was 12.5 days. No patient was readmitted, developed peripancreatic fluid collections, required interventional radiology procedures, or underwent repeat surgery.
In CP, interposing an anatomic barrier, such as the transverse mesocolon, between the two pancreatic remnants is a simple maneuver that, if on one hand, adds little to the complexity of the operation, on the other, provides insights into the origin of PF after CP.
Langenbeck s Archives of Surgery 02/2012; 397(6):1013-21. · 1.81 Impact Factor
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Ugo Boggi,
Fabio Vistoli,
Gabriella Amorese,
Rosa Giannarelli,
Alberto Coppelli,
Rita Mariotti,
Lorenzo Rondinini,
Massimiliamo Barsotti,
Stefano Signori, Nelide De Lio,
Margherita Occhipinti,
Emanuela Mangione,
Diego Cantarovich,
Stefano Del Prato,
Franco Mosca,
Piero Marchetti
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ABSTRACT: Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate.
We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated.
Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min.
PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.
Transplantation 02/2012; 93(8):842-6. · 4.00 Impact Factor
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Enzo Capocasale,
Maurizio Iaria,
Fabio Vistoli,
Stefano Signori,
Maria Patrizia Mazzoni,
Raffaele Dalla Valle, Nelide De Lio,
Vittorio Perrone,
Gabriella Amorese,
Franco Mosca,
Ugo Boggi
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ABSTRACT: Background. Chylous leakage (CL) is a rare complication of laparoscopic live donor nephrectomy (LLDN). It may lead to malnutrition and immunological deficits because of protein and lymphocyte depletion.
Methods. Data from 208 consecutive LLDN performed at two institutions, between April 2000 and September 2010, were reviewed to identify the anatomical basis behind CL along with its diagnostic and therapeutic options.
Results. CL developed in eight donors (3.8%), as determined by high-volume drainage (range 540–800 mL/24 hr) of triglyceride-rich fluid. All donors were managed conservatively. Seven were put on total parenteral nutrition plus octreotide. One received low-fat diet, medium-chain triglyceride supplementation, and octreotide. Chylous fistulas resolved in 5 to 16 days (mean time 12.3 days). Drains were removed before hospital discharge, and no donor was readmitted and/or needed outpatient care.
Conclusions. CL is a potentially insidious and perhaps misdiagnosed complication after LLDN. It occurs in nearly 4% of LLDN and it seems to be uniquely associated to left-sided kidney recovery because of distinctive lymphatics distribution around the periaortic area of dissection. Conservative therapy is effective in most donors and should be initially attempted. Surgical ligatures or fibrin sealants may be indicated in case of refractory CL before the arising of malnutrition and/or relevant immunodeficiency.
Transplantation 01/2012; 93(1):82-86. · 4.00 Impact Factor
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Ugo Boggi,
Stefano Signori,
Fabio Vistoli,
Gabriella Amorese,
Giovanni Consani, Nelide De Lio,
Vittorio Perrone,
Chiara Croce,
Piero Marchetti,
Diego Cantarovich,
Franco Mosca
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ABSTRACT: Pancreas transplant recipients continue to suffer high surgical morbidity. Current robotic technology provides a unique opportunity to test whether laparoscopy can improve the post-operative course of pancreas transplantation (PT). Current knowledge on robotic pancreas and renal transplantation was reviewed to determine feasibility and safety of robotic PT. Information available from literature was included in this review, together with personal experience including three PT, and two renal allotransplants. As of April 2011, the relevant literature provides two case reports on robotic renal transplantation. The author's experience consists of one further renal allotransplantation, two solitary PT, and one simultaneous pancreas-kidney transplantation. Information obtained at international conferences include several other renal allotransplants, but no additional PT. Preliminary data show that PT is feasible laparoscopically under robotic assistance, but raises concerns regarding the effects of increased warm ischemia time on graft viability. Indeed, during construction of vascular anastomoses, graft temperature progressively increases, since maintenance of a stable graft temperature is difficult to achieve laparoscopically. There is no proof that progressive graft warming produces actual damage to transplanted organs, unless exceedingly long. However, this important question is likely to elicit a vibrant discussion in the transplant community.
The Review of Diabetic Studies 01/2011; 8(1):28-34.
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Ugo Boggi,
Fabio Vistoli,
Gabriella Amorese,
Rosa Giannarelli,
Alberto Coppelli,
Rita Mariotti,
Lorenzo Rondinini,
Massimiliamo Barsotti,
Alberto Piaggesi,
Anna Tedeschi,
Stefano Signori, Nelide De Lio,
Margherita Occhipinti,
Emanuela Mangione,
Diego Cantarovich,
Stefano Del Prato,
Franco Mosca,
Piero Marchetti
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ABSTRACT: We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.
The Review of Diabetic Studies 01/2011; 8(2):259-67.
