Search

Background Physiologically regulated insulin secretion and euglycemia are achievable in type 1 diabetes (T1D) by islet or pancreas transplantation. However, pancreas transplant alone (PTA) remains a debated approach, with uncertainties on its relative benefits and risks. We determined the actual long-term (10 years) efficacy and safety of PTA in carefully characterized T1D subjects. Methods This is a single-centre, cohort study in 66 consecutive T1D subjects who received a PTA between April 2001 and December 2007, and were then all followed until 10 years since transplant. Main features evaluated were patient survival, pancreas graft function, C-peptide levels, glycemic parameters, and the function of the native kidneys. Results Ten-year actual patient survival was 92.4%. Optimal (insulin-independence) or good (minimal insulin requirement) graft function was observed in 57.4 and 3.2% of patients, respectively. Six (9.0%) patients developed stage 5 or 4 chronic kidney disease. In the remaining individuals bearing a successful PTA, eGFR decline per year was -2.29±2.69 ml/min/1.73m. Reduction of eGFR at 1 year post-PTA was higher in those with pre-PTA hyperfiltration and higher HbA1c concentrations; eGFR changes afterwards significantly correlated with diabetes duration. In recipients with normoglycemia at 10 years, 74% of normo- or micro-albuminuric subjects pre-PTA remained stable, and 26% progressed towards a worse stage; conversely, in 62.5% of the macro-albuminuric individuals albuminuria severity regressed. Conclusions These long-term effects of PTA on patient survival, graft function and the native kidneys support PTA as a suitable approach to treat diabetes in selected T1D patients.

Sex-related differences have been shown to deeply affect health-related aspects of patients. However, the lack of gender-specific analysis makes it difficult to advance personalized medicine in terms of a gender-based approach. The aim of the present study was to describe gender-specific features of patients diagnosed with heart failure (HF), with a focus on the clinical presentation. Data were collected from a properly designed database and referred to an Italian hospital. Patients aged ≥18 years with a primary or secondary diagnosis of HF between 1 January 2012 and 31 December 2016 were included, and their demographic and clinical characteristics were analyzed according to gender. Of the 719 HF patients included, 317 (44.1%) were male and 402 (55.9%) were female. Women tended to be older compared to men (82.4±8.8 years and 77.1±10.6 years, respectively). As for clinical presentation, 62.1% of female and 38.3% of male patients had preserved ejection fraction, and 56.1% of men and 58.2% of women suffered from atrial fibrillation. The left atrium was partially compromised in 62.4% of male and 63% of female patients, while right atrium dysfunction tended to be more frequent in male patients compared to female patients (29.1% and 25.5%, respectively). In conclusion, gender-specific features of a cohort of HF patients from a clinical setting were accurately described.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Objective. To provide estimates of patients with rheumatoid arthritis (RA) eligible for biotechnological therapy and to evaluate their healthcare costs. Method. An observational analysis was performed based on data-linkage between administrative databases of selected Italian Regional/Local healthcare departments. Data were then re-proportioned to the Italian population. Patients with RA diagnosis defined by discharge diagnosis and/or exemption code during 01/01/2013- 31/12/2017 were included. The criteria applied to evaluate the elegibility for biotechnological therapy were: 1) methotrexate (MTX)-treatment failure ≥6 months and start of a different conventional-synthetic diseasemodifying antirheumatic drugs (csDMARD); 2) corticosteroid ≥6 months with dosage ≥7.5 mg/die; 3) MTX-contraindication (therapy or hospitalization for renal damage/interstizial lung disease/hepatic failure). Mean annual costs per patient included drugs, hospitalizations, outpatient services. Results. Data re-proportioned to the Italian population estimated 318,328 RA patients: 43,361 with, 274,967 without biotechnological agents. Among the latter, 26,487(9.6%) patients met ≥1 criteria applied for eligibility: 1,896 had MTX-treatment failure and started another csDMARD; 15,833 received corticosteroid ≥7.5 mg/die; 7,788 had MTX-contraindication. Regarding patients fulfilling two criteria, 107 had MTX-treatment failure followed by another csDMARDs and corticosteroid ≥7.5 mg/die, 53 were treated with another csDMARDs after MTX-treatment failure and also presented MTX-contraindication, 810 had corticosteroid ≥7.5 mg/die and MTX-contraindication. Mean total annual costs for patients estimated eligible for biotechnological therapy was € 3,132, of which € 177 related to drugs indicated for RA and € 2,955 related to other direct costs. Conclusions. According to our estimates, around 10% RA patients not currently treated with biotechnological agents are eligible for such therapies, highlighting a trend of under-use in clinical practice for RA management.

Background and importance Novel treatment approaches for the management of severe refractory asthma include monoclonal antibodies (Mabs). Aim and objectives The study aimed to estimate the number of the most suitable patients with severe uncontrolled asthma who are eligible for new Mabs therapy and related costs in the Veneto region (Italy). Material and methods The regional administrative database was retrospectively analysed to identify specific eligibility and assessment criteria. All patients aged ≥6 years with an exemption code for asthma (007) (level 1 patients (L1)) between 1 January 2011 and 31 December 2016 were screened. The following parameters were considered in succession: spirometry (codes: 89.37, 89.38)–(level 2 patients (L2)); inhaled corticosteroids (ICS) in combination with long acting beta adenoreceptor agonists (LABA) and/or theophylline (ATC: R03DA04), and/or antileucotriene (ATC: R03DC), and/or anticholinergics (ATC: R03BB)–(level 3 patients (L3)); high dose ICS therapy (ATC: R03BA, R03AK)–(level 4 patients (L4)); adherence to each medication–(level 5 patients (L5)); asthma hospitalisation (ICD9: 493) or treatment with systemic corticosteroids (ATC: H02)–(level 6 patients (L6)). For each patient level, the mean annual healthcare costs per patient, based on total resource consumption, were assessed. Results For a total of 4.6 million beneficiaries, aged ≥6 years, 103 138 (2.2%) patients were screened (L1). Spirometry tests were prescribed in 28 611 patients (27.7%) (L2), of whom 13 432 (46.9%) had a prescription for ICS with LABA or other agents (L3). In 5782 (43%) patients treated with previous combinations, high dose ICS therapy was prescribed (L4), and of them, 3307 (57.2%) were treatment adherent (L5) and 1136 (35.2%) had a hospital admission for asthma or treatment with systemic corticosteroids (L6). For this last level of patients, centres specialising in Mabs prescription evaluated eligibility. Total costs of the illness according to disease progression were €1279.6 for L1, €1567.7 for L2, €2045.3 for L3, €2524.2 for L4, €3233.2 for L5 and €4326.2 for L6; overall asthma related treatment and hospitalisation costs were €274.2 for L1, €400.1 for L2, €598.5 for L3, €784.3 for L4, €1118.4 for L5 and €1449.9 for L5. Conclusion and relevance This analysis allowed estimation of the number of asthma patients eligible for Mabs therapy in the Veneto region. Our findings on healthcare costs highlighted that the average cost per patient increased by severity level. Post marketing, it will be possible to assess the appropriateness of Mabs prescriptions through indicators such as over- and under-use. References and/or acknowledgements No conflict of interest.

Background The European Medicines Agency has recently approved rivaroxaban for the prevention of atherothrombotic events in patients with coronary artery disease (CAD) and peripheral arterial disease (PAD). Purpose The present study aimed at analysing the prevalence of CAD and PAD among the health-assisted population and to estimate the pharmaceutical expenditure. Material and methods Data have been obtained by retrospectively analysing a regional healthcare database between 1 January 2017 and 31 December 2017. We included adult patients (≥18 years) with a diagnosis of CAD (at least one prescription of nitrates and/or CAD diagnosis at hospital discharge) and a diagnosis of PAD (at least one prescription of antiplatelet drugs with concomitant prescription of anti-hypertensive agents or lipid-lowering agents and/or PAD diagnosis at hospital discharge). Patients were characterised over the period 2009–2016 for comorbidities (diabetes mellitus, heart failure, chronic kidney disease, cardiovascular event), during 2016 for drug use. Treatment adherence was calculated using the Medication Possession Ratio. Results More than 4.9 million health-assisted participants, 8.8% (430,254, mean age 74.2 years) received a diagnosis of CAD or PAD (41.2% PAD, 30.4% CAD, 28.4% both). Forty-two per cent (180,551) of patients had at least one comorbidity. Most frequently prescribed cardiovascular agents were anti-hypertensives (85%), antiplatelet drugs (58.7%), lipid-lowering drugs (53%) and anticoagulants (17.2%). Among patients treated with antiplatelet drugs, 36.2% were adherent to treatment. Considering the actual price of rivaroxaban, the pharmaceutical expenditure for one-year treatment in the considered region resulted at €266 million (€38 million is the current pharmaceutical expenditure for new anticoagulant therapies for 2018). Applying this analysis for patient sub-groups, the estimation was €191 million for patients with CAD or PAD, €75 million for patients with both and €112 million for those with at least one comorbidity. Considering patients adherent to antiplatelet treatment, the estimation was €58 million. Conclusion Nearly one out of ten health-assisted subjects had CAD and PAD diagnosis, in accordance with that already published for the national population. Pharmaceutical costs’ estimations represent the maximal costs as they did not consider the possible reduction in drug prices negotiated by the National Medicines Agency, considering the significant market increase and redeemability limitations. References and/or acknowledgements No conflict of interest.

Background:Ankylosing spondylitis (AS) is a chronic rheumatologic condition requiring lifelong treatments. To date, few real-world studies on AS patients in Italy are reported.Objectives:Aims of the study were to evaluate treatment patterns and to analyse pharmacoutilization on patients affected by AS in a real-world setting of Italian clinical practice.Methods:This observational study was based on administrative databases of a pool of Italian settings. A retrospective cross-sectional analysis was performed for years 2015-2017 to evaluate AS-diagnosed patients and, among them, to estimate percentage of treated and untreated ones. Patients were included if having a hospitalization discharge diagnosis at any level of AS (ICD-9-CM: 720.0) or exemption code for AS (054.720.0). Index date (ID) was date in which patients met one of the inclusion criteria. Patients with a prescription for drugs indicated for AS [non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) - targeted synthetic (tsDMARDs) and biological (bDMARDs)] at ID were defined “treated”. Patients without such drug prescriptions at ID were considered “untreated”. To analyse treatment patterns of b/tsDMARDs-treated patients a longitudinal cohort study was conducted considering as inclusion periods the year 2014 and a period from 01/07/2016 to 30/06/2017. ID was date of first b/tsDMARDs prescription during inclusion period. Follow-up (F-up) lasted one year after ID. The interruption of treatment was defined as the absence of prescriptions in the last 3 months of F-up.Results:For cross-sectional-cohort: AS-diagnosed patients were 4,824 in 2015, 5,357 in 2016, 5,894 in 2017. In all years analysed, about 50% of patients were male. Mean age±SD ranged from 51.5±13.7 (2015) to 52.4±14.0 (2017). Untreated patients were 33.6% (2015), 35.1% (2016) and 37.9% (2017), while patients in therapy with b/tsDMARDs were 22.7% (2015), 22.3% (2016) and22.2% (2017). The remaining percentage of patients were treated with csDMARDs/NSAIDS: 43.7% (2015), 42.6% (2016), 39.9% (2017)). In 2015 and 2016 all b/tsDMARDs-treated patients were in therapy with anti-TFN agents, while the advent of IL-inhibitors was observed starting from 2017 (8.2% b/tsDMARDs-treated patients with IL-inhibitors). For longitudinal-cohort: in 2014, 310 patients had a b/tsDMARDs prescription and during 1-year F-up 11.9% of them interrupted the treatment after a mean time ±SD of 83.3±66.9 days. Of the 183 patients who had a prescription of b/tsDMARDs at ID during 2016-2017, 22.4% had a treatment interruption after a mean time±SD of 134.4±86.1 days during F-up.Conclusion:This real-world study provided insights on AS treatment patterns. Preliminary results showed that approximately one third of AS patients are untreated and about one in five are treated with b/tsDMARDs. Despite the improvement in treatment duration observed from 2014 to 2016/17, still 22.4% of b/tsDMARDs-treated patients interrupted therapy in the most recent cohort. A larger sample size is needed to confirm results.Disclosure of Interests:Valentina Perrone: None declared, Serena Losi Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Erica Filippi Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Silvia Antonelli Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Massimo Giovannitti Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Elisa Giacomini: None declared, Diego Sangiorgi: None declared, Luca Degli Esposti: None declared

No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators.

The first successful kidney transplantation between identical twins, performed in Boston in 1954, opened the clinical transplant era. Ever since, kidney transplantation has become one of the milestones of the recent history of medicine, whilst saving millions of lives. Although the nature of this extraordinary accomplishment is multifactorial, the successful outcome of a renal transplant begins with an impeccable surgery. This chapter will illustrate the state of the art of kidney transplant surgery in the recipient.

Pancreas transplantation is the only therapy that can restore insulin independence in beta-cell penic diabetic recipients. Because of the need for life-long immunosuppression and the intial surgical risk associated with the transplant procedure, Pancreas transplantation is a therapeutic option only in selected diabetic patients. Based on renal function, three main populations of diabetic recipients of a pancreas transplant can be identified: uremic patients, posturemic patients (following successful kidney transplantation), and non-uremic patients. Uremic patients are best treated by simultaneous kidney-pancreas transplantation with grafts obtained from the same deceased donor. Posturemic patients can receive a pancreas after kidney transplantation, if the previous renal graft has a good functional reserve. Non-uremic patients can receive a pancreas alone transplant if their diabetes is poorly controlled, despite optimal insulin therapy, suffer from unawareness hypoglycemia events and/or develop progressive chronic complications of diabetes. The results of pancreas transplantation have improved over the years and are currently not inferior to those of renal transplantation in non-diabetic recipients. A functioning pancreatic graft can prolong the life of diabetic recipients, improves their quality of life, and can halt, or reverse, the progression of chronic complications of diabetes. Unfortunately, because of ageing of donor population and lack of timely referral of potential recipients, the annual volume of pancreas transplants is declining. Considering that the results of pancreas transplantation depend on center volume, and that adequate center volume is required also for training of newer generations of transplant physcians and surgeons, centralization of pancreas transplantation activity should be considered.

Robotic assistance improves surgical dexterity in minimally invasive operations, especially when fine dissection and multiple sutures are required. As such, robotic assistance could be rewarding in the setting of robotic pancreatoduodenectomy (RPD). RPD was implemented at a high volume center with preemptive experience in advanced laparoscopy. Indications, surgical technique, and results of RPD are discussed against the background of current literature. RPD was performed in 112 consecutive patients. Conversion to open surgery was required in three patients, despite nine required segmental resection and reconstruction of the superior mesenteric/portal vein. No patient was converted to laparoscopy. A pancreato-jejunostomy was created in 106 patients (94.6 %), using either a duct-to-mucosa (n = 82; 73.2 %) or an invaginating (n = 24; 21.4 %) technique. Pancreato-gastrostomy was performed in one patient, the pancreatic duct was occluded in two patients, and a pancreatico-cutaneous fistula was created in three patients. Mean operative time was 526.3 ± 102.4 in the entire cohort and reduced significantly over the course of time. Experience was also associated with reduced rates of delayed gastric emptying and increased proportion of malignant tumor histology. Ninety day mortality was 3.6 %. Postoperative complications occurred in 83 patients (74.1 %) with a median comprehensive complication index of 20.9 (0–30.8). Clinically relevant pancreatic fistula occurred in 19.6 % of the patients. No grade C pancreatic fistula was noted in the last 72 consecutive patients. RPD is safely feasible in selected patients. Implementation of RPD requires sound experience with open pancreatoduodenectomy and advanced laparoscopic procedures, as well as specific training with the robotic platform.

Recent findings from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study showed that long-term improved glycemic control in patients with type 1 diabetes with normal renal function and normoalbuminuria can delay development of impaired renal function by at least 6.5 years, although the reduction in the relative risk of end-stage renal disease (ESRD) was not significant. The unanswered question is: can improvement of glycemic control delay the onset of ESRD in patients with established diabetic nephropathy? In this context, pancreas transplantation (PATx) can be considered the most effective intervention to restore normoglycemia. Can this aggressive/experimental intervention be applied to arrest/retard renal function decline? To answer this question, this review summarizes the relevant findings from observational studies conducted in cohorts of patients, followed up for 4 to 15 years, who underwent PATx. These noncontrolled studies provided positive answers to the earlier question, principally concerning a significant decrease in albumin excretion levels. However, current drugs used to prevent rejection could impair renal function, principally in recipients with low pretransplant estimated glomerular filtration rate (ie,60 mL/min). Unfortunately, all these studies had shortcuts that qualify interpretation of the findings. First, it is unclear how much initial estimated glomerular filtration rate loss results from nephrotoxic effect of antirejection drugs, and how much results from improved glycemia and its impact on the reduction of hyperfiltration. Second, the study designs did not consider the wide variation in rates of renal function loss observed in patients with established nephropathy (ie, one third are nonprogressors, one third are slow progressors, and one third are rapid progressors). Third, all studies were observational in nature and clinical trials are needed to properly evaluate the effectiveness of normalization of hyperglycemia through PATx on postponing the onset of ESRD in type 1 diabetes.

The enhanced dexterity offered by robotic assistance could be excessive for distal pancreatectomy but not enough to improve the outcome of laparoscopic pancreaticoduodenectomy. Total pancreatectomy retains the challenges of uncinate process dissection and digestive reconstruction, but avoids the risk of pancreatic fistula, and could be a suitable operation to highlight the advantages of robotic assistance in pancreatic resections. Eleven laparoscopic robot-assisted total pancreatectomies (LRATP) were compared to 11 case-matched open total pancreatectomies. All operations were performed by one surgeon during the same period of time. Robotic assistance was employed in half of the patients, based on robot availability at the time of surgery. Variables examined included age, sex, American Society of Anesthesiologists score, body mass index, estimated blood loss, need for blood transfusions, operative time, tumor type, tumor size, number of examined lymph nodes, margin status, post-operative complications, 90-day or in-hospital mortality, length of hospital stay, and readmission rate. No LRATP was converted to conventional laparoscopy, hand-assisted laparoscopy or open surgery despite two patients (18.1 %) required vein resection and reconstruction. LRATP was associated with longer mean operative time (600 vs. 469 min; p = 0.014) but decreased mean blood loss (220 vs. 705; p = 0.004) than open surgery. Post-operative complications occurred in similar percentages after LRATP and open surgery. Complications occurring in most patients (5/7) after LRATP were of mild severity (Clavien-Dindo grade I and II). One patient required repeat laparoscopic surgery after LRATP, to drain a fluid collection not amenable to percutaneous catheter drainage. One further patient from the open group required repeat surgery because of bleeding. No patient had margin positive resection, and the mean number of examined lymph nodes was 45 after LRATP and 36 after open surgery. LRATP is feasible in selected patients, but further experience is needed to draw final conclusions.

Laparoscopic resection of liver tumors located in the posterosuperior segments is a challenging operation that could be facilitated by robotic assistance. Laparoscopic resection of 12 tumors located in posterosuperior segments (IVa: 1; VII: 5; VIII: 6) was carried out under robotic assistance. All patients had a single tumor nodule. Data were collected prospectively and analyzed retrospectively. Surgery required a mean of 260.4 min (115–430) and was completed laparoscopically in all but one patient, who required conversion to mini-laparotomy because of intolerance of pneumoperitoneum (8.3 %). Mean estimated blood loss was 252.7 ml (50–600), making transfusion necessary in 3 patients (25.0 %). Post-operative complications occurred in 4 patients (33.3 %), being of Clavien–Dindo grade II in 3 patients (25.0 %) and Clavien–Dindo grade IV in 1 patient (8.3 %). Reoperation was required in 1 patient, who subsequently had a long hospital stay, because of decompensated cirrhosis. Median length of hospital stay was 8.5 days (7–96). No patient was readmitted. Pathology showed hepatocellular carcinoma in 7 patients (58.3 %), liver metastasis in 2 patients (16.6 %), and hepatic adenoma, focal nodular hyperplasia, and hemangioma in one patient each (8.3 %). All patients had a margin negative resection. After a mean follow-up period of 21.4 months (±24.4), no patient with malignant histology developed recurrence. Our initial experience confirms that laparoscopic robot-assisted resection of tumors located in the posterosuperior segments is feasible. Further experience is needed before final conclusions can be drawn and meaningful comparison with other surgical techniques becomes possible.

Laparoscopic pancreaticoduodenectomy (LPD) is gaining momentum, but there is still uncertainty regarding its safety, reproducibility, and oncologic appropriateness. This review assesses the current status of LPD. Our literature review was conducted in Pubmed. Articles written in English containing five or more LPD were selected. Twenty-five articles matched the review criteria. Out of a total of 746 LPD, 341 were reported between 1997 and 2011 and 405 (54.2 %) between 2012 and June 1, 2013. Pure laparoscopy (PL) was used in 386 patients (51.7 %), robotic assistance (RA) in 234 (31.3 %), laparoscopic assistance (LA) in 121 (16.2 %), and hand assistance in 5 (0.6 %). PL was associated with shorter operative time, reduced blood loss, and lower rate of pancreatic fistula (vs LA and RA). LA was associated with shorter operative time (vs RA), but with higher blood loss and increased incidence of pancreatic fistula (vs PL and RA). Conversion to open surgery was required in 64 LPD (9.1 %). Operative time averaged 464.3 min (338–710) and estimated blood 320.7 mL (74–642). Cumulative morbidity was 41.2 %, and pancreatic fistula was reported in 22.3 % of patients (4.5–52.3 %). Mean length of hospital stay was 13.6 days (7–23), showing geographic variability (21.9 days in Europe, 13.0 days in Asia, and 9.4 days in the US). Operative mortality was 1.9 %, including one intraoperative death. No difference was noted in conversion rate, incidence of pancreatic fistula, morbidity, and mortality when comparing results from larger (≥30 LPD) and smaller (≤29 LPD) series. Pathology demonstrated ductal adenocarcinoma in 30.6 % of the specimens, other malignant tumors in 51.7 %, and benign tumor/disease in 17.5 %. The mean number of lymph nodes examined was 14.4 (7–32), and the rate of microscopically positive tumor margin was 4.4 %. In selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is feasible and safe.

Background Laparoscopic pancreaticoduodenectomy is feasible, but requires adaptations to established surgical techniques. The improved dexterity offered by robotic assistance provides the opportunity to see whether laparoscopic pancreaticoduodenectomy can be performed safely when faithfully reproducing the open operation. Methods Patients were selected for robotic pancreaticoduodenectomy when generally suitable for laparoscopy. Obese patients were excluded, and those with pancreatic cancer were highly selected. A prospectively designed database was used for data collection and analysis. Results Of 238 patients undergoing pancreaticoduodenectomy, 34 (14·3 per cent) were operated on robotically. No procedure was converted to conventional laparoscopy or open surgery, despite three patients requiring segmental resection of the superior mesenteric/portal vein and reconstruction. The mean duration of operation was 597 (range 420–960) min. The mean number of lymph nodes retrieved and analysed from patients with neoplasia was 32 (range 15–76). Four patients required blood transfusions and five developed postoperative complications exceeding Clavien–Dindo grade II. There were four grade B pancreatic fistulas. One patient died on postoperative day 40. Excess mean operative cost compared with open resection was €6193. Conclusion Selected patients can safely undergo robotic pancreaticoduodenectomy. The main downsides are high costs and prolonged operating times compared with open resection.

Background Originally introduced for cutaneous T-cell lymphomas and autoimmune diseases, extracorporeal photopheresis (ECP) has been proven effective to reverse allograft rejection. The aim of the present work was to show the results of a single-center experience with ECP for the treatment of biopsy-proven rejection in selected liver transplant (LT) recipients. Patients and methods A retrospective review of five LT patients (M:F = 4:1; median age 51 years) undergoing ECP for biopsy-proven allograft rejection between January 1996 and December 2003. In this period 476 LT were performed on 441 patients. Results The indications for LT were three cases of HCV-related cirrhosis, complicated by hepatocellular carcinoma in two; one HBV-HDV-alcoholic cirrhosis; and one fulminant HBV hepatitis. All patients received calcineurin-inhibitor (CNI)-based immunosuppression with induction using anti-IL2R monoclonal antibodies. Indications for ECP were: ductopenic rejection in one patient with HCV recurrence; steroid-resistant acute rejection in two; acute rejection in a major ABO-mismatched liver graft; and one acute rejection in a patient with a proven allergy to steroids. The median interval from LT to inception of ECP was 43 days. The median number of ECP sessions per patient was 20. During the course of ECP, two patients tested positive for CMV antigenemia, associated in one case with bacterial pneumonia. All patients tolerated ECP and there were no procedure-related complications. At a median follow-up of 7.9 months after start of ECP, neither rejection relapses nor HCV/HBV recurrences have been observed. Three patients are off ECP with complete reversal and low-dose immunosuppression. Two patients are still receiving ECP with full-dose immunosuppression: one has achieved normal liver function but ECP is indicated due to a major ABO-incompatible liver graft, while the other patient's liver functions have not yet returned to baseline values.

Context Isolated involvement of an arterial segment in pancreatic tumors occurs infrequently and does not necessarily mean tumor unresctability being possibly caused by tumor location rather than by excessive growth. Objective We report on the outcome of a highly selected group of patients undergoing pancreatectomy plus resection of an isolated arterial segment at a single Institution. Methods From January 1993 to May 2011 resection of an isolated arterial segment was performed during 26 pancreatectomies. There were 12 males (46.2%) and 14 females (53.8%) with a mean age of 63.6 years. One patient was operated by robotic surgery. Two patients underwent total pancreatectomy (7.7%), 5 pancreaticoduodenectomy (19.2%) and 19 distal splenopancreatectomy (73.1%). Resected arterial segments were celiac trunk (CT) (n=14), hepatic artery (HA) (n=8), CT and HA (n=4). In 6 patients the hepatic arterial flow was re-established by end-to-end anastomosis (n=1), transposition of the left gastric artery (n=1) and interposition of a saphenous vein jump-graft (n=4). Multivisceral resection was required in 9 patients. Results Final pathology disclosed ductal adenocarcinoma (DA) in 18 patients (69.2%), other pancreatic tumor types or periampullary carcinoma in 5 (19.2%) patients and metastatic tumor in 3 patients (11.5%). Fifteen DA patients were node positive (83.3%). Post-operative morbidity and mortality were 55.5% and 3.8%, respectively. After a mean follow up period of 111 months (range 5-225 months), actual survival rate was 64% at 1 year and 20% at 3 years. Equivalent figures for DA were 30% and 15%, respectively. These data favorably compare with an historical cohort of patients with locally advanced DA undergoing palliation without resection. No patient developed local recurrence, despite none received pre- or post-operative radiation. Conclusions In patients affected by DA the resection remains key for cure and possibly provides the best palliative treatment. Highly selected patients with isolated involvement of CT and/or HA may undergo pancreatectomy with results similar to patients without vascular involvement and superior to those offered by palliation or medical therapy alone. The lack of local recurrence seems to be a relevant treatment endpoint., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

BackgroundOnly 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.Methodology/principal findingsHigh-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 28 days), carefully selected according to their outcome (OS30 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.Conclusions/significanceThrough 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.

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.

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.

We retrospectively evaluated the outcome of the surgical treatment of patients with renal cell carcinoma (RCC) and extensive inferior vena cava (IVC) involvement. Our aim was to investigate if a particular surgical technique could reduce morbidity and complications associated with this condition.From 1996 to 2007, 22 patients with RCC and extensive IVC involvement underwent radical surgical treatment with the intention to avoid, whenever possible, sternotomy and cardiopulmonary bypass. The level of the tumor thrombus was I (2 cm above the renal vein) in 2 patients, II (below the intrahepatic vena cava) in 9 patients, III (intrahepatic vena cava below the diaphragm) in 7 patients, and IV (atrial) in 4 patients. Extracorporeal vascular bypass was used for 4 patients with level IV and for 2 patients with level III tumor thrombi, with hypothermic circulatory arrest in 2 patients. Extensive liver mobilization techniques were adopted in 16 patients. Overall and cancer-specific survival (CSS) were analyzed based on tumor extent (N0M0, N+M+), pathologic stage (pT3b, pT3c, pT4), thrombus level, and caval wall infiltration.Two patients died within 1 month of surgery and the remaining 20 patients have a mean follow-up of 32.2 months (range 6-90): 8 are alive (overall survival 40%), but 2 with disease (CSS 30%). A total of 10 severe complications developed in 8 patients (36%). Both overall and CSS were significantly associated with tumor stage (Log-rank P = 0.0237 and 0.0465), presence of nodal or systemic metastases (Log-rank P = 0.0835 and 0.0669; Wilcoxon's test P = 0.0407 and 0.0411), and caval wall infiltration (Log-rank P = 0.0200 and 0.0418).Despite the low overall survival, related to the high percentage of nodal and systemic metastases, aggressive surgical management with resection of synchronous metastatic disease for symptom palliation and cytoreduction, followed by immunotherapy is justified in this setting. A transabdominal approach to RCC and IVC involvement, even in patients with level III thrombus, can provide the surgeon with an exposure similar to thoracoabdominal incisions without the complications associated with thoracotomy.

s / Pancreatology 546 staining; six fields for each patient) in surgical specimens. We evaluated the PI by Ki-67 staining for grading in 7/21 tumors (expressed by number of positive nuclei/total nuclei). Results: Pathological analysis demonstrated 5 ADN, 5 BRD and 12 WDC. All ADN were associated with pattern A, showing high MVD (463 vessels/mm2); 3/4 lesions showing pattern B1 were BRD, with middle level of MVD (373 vessels/mm2) while 3/4 lesions with pattern B2 were WDC, demonstrating low level of MVD (vessels/mm2, p 0.05). Discussion: In our opinion the MDCT post-contrastographic pattern and the MVD of PNET can suggest their biological behavior. The CA system can help the pathologist to have a rapid evaluation of Ki-67 for grading in PNET.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal among solid tumors. Only a subset of patients benefit from chemotherapy, and identification of novel prognostic factors is warranted. Recently, miRNAs emerged as a pivotal class of regulators for multiple genes involved in cancer, including PDAC (Giovannetti et al, Cancer Res 2010), and miRNA expression pattern classified tumors better than mRNA data (Lu et al, Nature 2005), suggesting their use for diagnostic purposes. However, high-throughput arrays detecting more than 1000 miRNAs are opening new opportunities to evaluate whether their profiles can also predict clinical outcome. Therefore, the present study evaluated whether comprehensive miRNA expression profiling by microarray technology can predict overall survival (OS) in resected PDAC patients. High-resolution miRNA profiles were obtained with the Toray's 3D-GeneTM miRNA chip, detecting 1200 types of human miRNA. RNA was isolated from formaldehyde fixed paraffin embedded primary tumors of 26 stage-pT3N1Mx homogeneously treated patients (gemcitabine 1000 mg/m2/day on days 1/8/15, every 28 days), selected according to their outcome (OS 30 months). Microarray slides of the 19 samples that passed RNA quality check were scanned using 3D-GeneTM Scanner 3000 with appropriate photomultiplier settings for red channel. Each microarray was scanned three times, and then merged into one dataset analyzed. Highly stringent statistics included t-test, Spearman ranked correlation to generate a distance matrix, and iterative approaches. Unsupervised hierarchical analysis revealed that the PDAC specimens clustered according to their long/short OS classification, while the feature selection algorithm RELIEF identified the top 10 discriminating miRNAs between the two groups. MiR211 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 RT-PCR in an independent cohort of laser microdissected tumors from 60 resected stage-pT3N1Mx PDAC patients treated with the same gemcitabine regimen. Patients with low miR211 expression, according to median value (12.8 a.u. calculated as ΔCt vs. RNU6), 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 miR211 expression was an independent factor of poor prognosis for OS (hazard ratio 2.3, P=0.03) after adjusting for all the factors influencing clinical outcome. In conclusion, through comprehensive microarray analysis and PCR validation we identified miR211 as prognostic factor in resected PDAC. This miRNA was already associated with melanoma invasiveness, but our results prompt further prospective studies as well as research on miR211 biological role in PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 186. doi:1538-7445.AM2012-186

A Kaposi's sarcoma case with involvement of the gastrointestinal tract resulting in an unusual clinical syndrome characterized by diarrhea and protein-losing enteropathy is described. A careful examination of the literature reveals only one account of this rare pathologic condition.