Re-operation in pancreas transplantation.

BACKGROUND: Surgical complications in pancreas transplantation are associated with increased morbidity and graft loss. The purpose of our study was to determine the frequency of re-operation in early and late postoperative of pancreas transplantation and its impact in relation to graft survival, patient survival, and hospital mortality. METHODS: We conducted a retrospective study of 238 pancreas transplants performed from 2001 to 2011. We analyzed surgical complications that led to the early and late re-operations by type of transplantation and its relation to pancreas graft survival, patient survival, and hospital mortality. RESULTS: We studied 61 re-operated patients (25.63%), 58 patients with early re-operation and 3 with late re-operation. The median of re-operations per patient was 1.48 (range, 1 to 5). Seventy-five surgical complications required 90 re-operations. The causes of early re-operations were bleeding (8.8%), pancreas graft thrombosis (6.3%), pancreatitis (2.9%), bowel obstruction (2.1%), leaks (2.1%), and evisceration (1.7%). The hospital mortality rate was 0.43%. Pancreas graft survival at 1 and 5 years is higher in the group of non-re-operated than in the re-operated group (98% vs 74% and 93% vs 57%; P = .0001). Patient survival at 1 year is slightly higher in the non-re-operated group, but with no significant differences (99% vs 97%), and at 5 years the patient survival in the non-re-operated group is higher than in the re-operated group (98% vs 91%; P = .011). CONCLUSIONS: Surgical complications required re-operations that were associated with higher morbidity and lower pancreas graft and patient survival.

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

[Indications for laparoscopic pancreas operations: results of a consensus conference and the previous laparoscopic pancreas register]. / Indikation zur laparoskopischen Pankreasoperation: Ergebnisse einer Konsensuskonferenz und des bisherigen laparoskopischen Pankreasregisters.

Laparoscopic pancreatic surgery is not common practice in Germany and is only carried out in approximately 20 clinics but with an increasing trend. The reasons for this are manifold, such as the current selection of patients and both skills in laparoscopic and pancreatic surgery are necessary to perform this operation safely. In 2008 a registry called "Laparoscopic pancreatic surgery" was implemented to collect enough data in Germany to find out whether the resection is safe, feasible and beneficial for the patient.For further development of new laparoscopic techniques new data is needed. A group of experts performing laparoscopic pancreatic surgery in Germany supplied their data for the German registry for laparoscopic pancreatic resection and a consensus conference about the indications became necessary. This consensus conference discussed in particular the indications for laparoscopic pancreatic resection. A consensus was found by all members of the conference utilizing currently available evidence-based data.It was suggested that all data of laparoscopic pancreatic surgery should be evaluated in the German Registry. A consensus was made which diseases were either suitable for laparoscopic resection or not suitable or suitable in selected cases.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Simultaneous pancreas-kidney transplantation: is the failure of the grafts also simultaneous?

INTRODUCTION: It is well known that after a simultaneous pancreas and kidney transplantation (SPKT) there is a higher incidence of pancreatic graft loss in the acute period, due to technical problems. However, there is little information about the survival of pancreatic and kidney grafts 1 year after transplantation. AIMS: To analyze the causes of long-term graft loss of SPKT in our hospital and to determine if this loss occurs simultaneously or is isolated. PATIENTS AND METHODS: We analyzed the data of 63 SPKTs performed between February 1983 and October 2005, including the cases with normal renal and pancreatic function after 1 year of transplantation, and with a loss of one or two organs during the follow-up period (8 +/- 4 years). We defined simultaneous SPKT failure as failure that occurs at the same time or when the period between pancreatic and renal graft failure is shorter than 9 months. RESULTS: In 28 patients (44%), there was a simultaneous graft failure, whereas in 35 (56%) the loss of function occurred in only one organ or in both, but separately. Death was responsible for 75% (21/28) of simultaneous graft losses, representing 25% (9/35) of isolated graft failures. Cardiovascular disease was the leading cause of death. In 14 of 35 isolated graft failures, there was loss of renal and pancreatic function (11/14 kidney failed first) with a 2.9 +/- 2.3 years of interval. In 12 cases there was only loss of pancreatic function, whereas in nine cases the affected organ was the kidney. Graft chronic nephropathy and chronic rejection in the pancreas were the main causes of graft failure. CONCLUSIONS: The main cause of simultaneous SPKT failure is patient death; however, among isolated or separated SPKT failures, the kidney failed first, more frequently.

[Parathyroid carcinoma associated to secondary hyperparathyroidism in hemodialyzed patients. Two cases reports]. / Carcinoma de paratiroides asociado a hiperparatiroidismo secundario en pacientes en hemodiálisis.

Parathyroid carcinoma (PC) is an infrequent disease with a subtle initial presentation and a variable course, necessitating a high index of suspicion to make the correct diagnosis. In chronic failure patients on haemodialysis it becomes even more difficult to suspect this entity since the high prevalence of secondary hyperparathyroidism(SHP). Two patients with PC out of a series of 160 patients with moderate-to-severe SHP submitted for parathyroidectomy are reported. Their clinical features are compared with those of the twenty-two cases previously reported in the literature with a discussion of this pathology. Patients with PC showed higher blood levels of iPTH, total calcium, phosphate and total alkaline phosphatase than the SHP population. The final diagnosis of PC was made after histological study revealing capsular or blood vessel invasion.

Cytomegalovirus infection in simultaneous pancreas-kidney transplantation.

INTRODUCTION: In this open-label multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients between 1998 and 2000 were randomly assigned to tacrolimus or cyclosporine-microemulsion (ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil and short-term corticosteroids. We report the 3-year data related to the occurrence, severity and effect of cytomegalovirus (CMV) infections. The type of CMV prophylaxis and treatment was at the discretion of the investigator. RESULTS: The overall incidence of CMV infection was 34% with no difference in incidence between the tacrolimus and cyclosporine-ME treatment arms. Statistically significant fewer CMV infections occurred among patients who received ganciclovir (22%) than those who did not receive prophylaxis (42%; P = .0075) or were treated with acyclovir (43%; P = .0066). The CMV infection rate according to donor recipient CMV serological status was: D-/R- group 11%, which was lower than the D-/R+ group at 40% (P = .0035), the D+/R+ group at 37% (P = .0024), or the D+/R- group at 52% (P = .00001). Among the last three groups, the infection rate was lower in patients on ganciclovir than those with no prophylaxis or on acyclovir (22% vs 64%; P = .00001). The incidence of acute rejection episodes was higher among patients without ganciclovir prophylaxis. No difference was observed in actuarial patient, kidney, or pancreas survival rates between patients with versus without infection. CONCLUSIONS: Ganciclovir prophylaxis effectively prevented CMV infection in SPK transplant recipients, especially in higher risk groups. An effect of CMV prophylaxis on the incidence of rejection is possible.

[Hospital registry of pancreatic tumors. Experience of the Hospital Clínic in Barcelona (Spain)]. / Registro hospitalario de tumoraciones pancreáticas. Experiencia del Hospital Clínic de Barcelona.

OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.

Macrovascular events after kidney-pancreas transplantation in type 1 diabetic patients.

BACKGROUND: There are few studies concerning the effect of kidney-pancreas transplantation (KPTx) on the progression of macrovascular disease in type 1 diabetic patients. The aim of our study was to retrospectively evaluate the incidence of macrovascular events after functioning KPTx. MATERIALS AND METHODS: We studied 146 patients (96 men and 50 women) who had undergone KPTx from February 1983 to September 2001, with more than 1 year of evolution of both grafts functioning normally. The mean follow-up of the patients after KPTx was 5+/-3 years. RESULTS: Before KPTx, 29 patients displayed 42 macrovascular events. During the follow-up after transplantation, intermittent claudication remained in 25 patients (86.2%) with 11 new macrovascular events (1 stroke, 1 angina pectoris, 1 myocardial infarction, and 8 minor amputations) in 10 patients (34%). Among the 117 patients without antecedent macrovascular events prior to KPTx, 38 (32.5%) experienced a total of 63 macrovascular events (26 intermittent claudication, 4 stroke, 8 angina pectoris, 7 myocardial infarction, 11 minor amputations, and 7 major amputations). Before transplantation, 88.4% of the patients presented with hypertension, 42.5% a history of smoking, and 14.4% previous treatment for dyslipidmia. After transplantation, we observed an important reduction in the percentage of patients with hypertension (48.6%) and smoking (25.5%), without a change in the prevalence of dyslipemia (19.9%). Hypertension after transplantation was clearly associated with the appearance or persistence of macrovascular events. CONCLUSION: In our experience, 43% of the transplant recipients present with macrovascular events. It is important to note the elevated prevalence of cardiovascular risk factors in the patients who underwent KPTx.

Correlates of cognitive impairment in elderly residents of long term care institutions in the metropolitan area of Guadalajara, Mexico.

AIM: To determine the prevalence of cognitive impairment and to examine the correlation between demographic and social factors, the activities of daily living (ADL), and depression with cognitive function in elderly Mexicans living in nursing homes. DESIGN: Cross-sectional. SETTING: Fourteen nursing homes in Guadalajara. PARTICIPANTS: Data were drawn from a random sample of 451 elderly, aged 60-104 years. MEASUREMENTS: The Spanish versions of MMSE (Folstein), ADL index (Barthel), and the Geriatric Depression Screening (GDS) (Yesavage); demographic factors were obtained. RESULTS: The prevalence of cognitive impairment was 52.3%, with a cut-off of 19/20 (Bohnstedt). Cognitive impairment was significantly related to gender, educational level, activity participation, pension, ADL, and depression. CONCLUSION: The results indicate a higher prevalence of cognitive impairment than in other Mexican studies. The data are consistent with previous findings that cognitive impairment in the elderly is more common among females, those with a low level of education, the lack of participation in social/leisure activities, ADL dependencies, and depression.

Laparoscopic pancreatic surgery in patients with chronic pancreatitis.

BACKGROUND: In recent years, technological advances and technical refinements to laparoscopic instruments have encouraged some surgeons to explore the application of laparoscopic methods to benign disorders of the pancreas. The aim of this report was to evaluate the feasibility and outcome of laparoscopic pancreatic surgery in patients with chronic pancreatitis. METHODS: One group of five patients with disease of nonalcoholic origin localized in the body-tail of the pancreas underwent distal pancreatectomy with preservation of the splenic vessels; a second group of six patients with symptomatic pancreatic pseudocysts (alcoholic origin in four cases and idiopathic in two cases) underwent laparoscopic transgastric drainage. For distal pancreatectomy and spleen salvage, the patient's positioning was half-lateral decubitus with the left side up. Four ports were used. A comparison was made with 41 patients with chronic, pancreatitis who underwent conventional open distal pancreatectomy. For the patients with laparoscopic distal pancreatectomy, the mean operative time was 4 h (range 3-5). RESULTS: There were no pancreatic-related complications, but one patient was reoperated for perforation of duodenal ulcer. The mean hospital stay was 6 days and the mean time to resume normal daily activities was 3 weeks. Laparoscopic pseudocyst drainage was performed in four patients via laparoscopic anterior gastrostomy and two patients via laparoscopic intraluminal cystogastrostomy. The mean operative time was 100 min (range 60-160). There was no morbidity. The mean hospital stay was 5 days, and the mean time to resume normal daily activities was 2 weeks. CONCLUSION: This study provides information about the possibilities of performing laparoscopic surgery in patients with chronic pancreatitis. Laparoscopic distal pancreatectomy with preservation of the splenic vessels and laparoscopic transgastric drainage are feasible and safe techniques. They offer obvious advantages, such as reduction of the parietal damage to the abdomen, a shorter hospital stay, and an earlier postoperative recovery than can be obtained with conventional open pancreatic resection.

Outcome of laparoscopic pancreatic surgery: endocrine and nonendocrine tumors.

Laparoscopic pancreatic surgery (LapPS) for management of benign pancreatic tumors has still not been defined. This paper evaluates the feasibility and outcome of LapPS in patients with endocrine pancreatic tumors (EPTs) and cystic neoplasms of the pancreas (CyNP). Eighteen patients with benign pancreatic tumors underwent LapPS between January 1998 and May 2001. The indications were 10 EPTs (6 sporadic insulinomas, 1 multiple insulinoma of multiple endocrine neoplasia type 1, 2 nonfunctioning tumors, 1 VIPoma) and 8 CyNPs (3 serous cystadenomas, 5 mucinous cystic neoplasms). The laparoscopic procedure was performed using four ports with patients in the half-lateral position. Laparoscopic ultrasonography (LapUS) was used in all cases. Laparoscopic enucleation (LapE) was planned in five patients and performed in four (one conversion for tumor not found during laparoscopy). Laparoscopic pancreatic resection (LapPR) with spleen salvage was planned in 13 patients and performed in 12 (one conversion for metastatic VIPoma), with splenic vessel preservation in 11 patients and short gastric vessel preservation in 1. The average operating time was 3.5 hours after enucleation, 4.0 hours after distal pancreatectomy, and 5.0 hours after subtotal pancreatectomy. Pancreatic fistula was observed in two patients after LapE and in three patients after LapPR. Splenectomy for splenic abscess was performed 1 week after surgery in a patient with short gastric vessel splenic preservation. The average hospital stay was 5 days. We concluded that LapPS is a safe method for removing EPTs and CyNPs, although the incidence of pancreatic fistulas remains high. In selected patients LapPS offers significant benefit to patients: reduced trauma to the abdominal wall, short hospital stay, and a quick postoperative recovery.

Treatment and outcome of pancreatic venous graft thrombosis after kidney--pancreas transplantation.

BACKGROUND: Pancreas venous graft thrombosis after transplantation is the main non-immunological cause of graft failure and usually results in pancreatectomy. Duplex Doppler ultrasonography is the primary imaging technique for monitoring vascular patency after pancreas transplantation. This study reports the results of rescue treatments for pancreas graft thrombosis after simultaneous pancreas--kidney transplantation. METHODS: One hundred and ninety-six patients with insulin-dependent diabetes mellitus received a simultaneous pancreas--kidney transplantation. Venous graft thrombosis was diagnosed in 25 of these patients based on Doppler ultrasonographic findings. RESULTS: Total venous graft thrombosis was diagnosed in 20 symptomatic patients, of whom 14 required graft pancreatectomy. Surgical thrombectomy was attempted in six patients with preserved arterial supply and was successful in four. Partial venous graft thrombosis was diagnosed in five asymptomatic patients; one also had partial splenic artery thrombosis. Rescue graft procedures included systemic anticoagulation (one patient), arterial thrombolysis (one) and venous thrombolysis and/or mechanical venous thrombectomy (four episodes in three patients). Graft rescue was achieved in three patients treated by venous thrombolysis/thrombectomy. CONCLUSION: Doppler ultrasonography allows the appropriate selection of rescue treatment based on the findings of total or partial thrombosis.

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.

BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study. METHODS: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.