Marielda D’Ambra

Total pancreatectomy: indications, operative technique, and results: a single centre experience and review of literature.

The aims of this study were to identify the indications to perform a total pancreatectomy and to evaluate the outcome and quality of life of the patient who underwent this operation. A retrospective analysis of a prospective database, regarding all the patients who underwent total pancreatectomy from January 2006 to June 2009, was carried out. Perioperative and outcome data were analyzed in two different groups: ductal adenocarcinoma (group 1) and non-ductal adenocarcinoma (group 2). Twenty (16.9%) total pancreatectomies out of 118 pancreatic resections were performed. Seven (35.0%) patients were affected by ductal adenocarcinoma (group 1) and the remaining 13 (65.0%) by pancreatic diseases different from ductal adenocarcinoma (group 2) [8 (61.5%) intraductal pancreatic mucinous neoplasms, 2 (15.4%) well-differentiated neuroendocrine carcinomas, 2 (15.4%) pancreatic metastases from renal cell cancer and, finally, 1 (7.7%) chronic pancreatitis]. Eleven patients (55%) underwent primary elective total pancreatectomy; nine (45%) had a completion pancreatectomy previous pancreaticoduodenectomy. Primary elective total pancreatectomy was significantly more frequent in group 2 than in group 1. Early and long-term postoperative results were good without significant difference between the two groups except for the disease-free survival that was significantly better in group 2. The follow-up examinations showed a good control of the apancreatic diabetes and of the exocrine insufficiency without differences between the two groups. In conclusion, currently, total pancreatectomy is a standardized and safe procedure that allows good early and late results. Its indications are increasing because of the more frequent diagnose of pancreatic disease that involved the whole gland as well as intraductal pancreatic mucinous neoplasm, neuroendocrine tumors and pancreatic metastases from renal cell cancer.

Laparoscopic Distal Pancreatectomy in Benign or Premalignant Pancreatic Lesions: Is It Really More Cost-Effective than Open Approach?

BackgroundData regarding the quality of life in patients undergoing laparoscopic distal pancreatectomy are lacking and no studies have reported a real cost-effectiveness analysis of this surgical procedure. The aim of this study was to evaluate and compare the quality of life and the cost-effectiveness of a laparoscopic distal pancreatectomy with respect to an open distal pancreatectomy.MethodsForty-one patients who underwent a laparoscopic distal pancreatectomy and 40 patients who underwent an open distal pancreatectomy were retrospectively studied as regards postoperative results, quality of life and cost-effectiveness analysis. The Italian neutral version of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30, version 3.0, was used to rate the quality of life.ResultsPostoperative results were similar in the two groups; the only difference was that the first oral intake took place significantly earlier in the laparoscopic group than in the open group (P < 0.001). Regarding quality of life, the laparoscopic approach was able to ameliorate physical functioning (P = 0.049), role functioning (P = 0.044) and cognitive functioning (P = 0.030) and reduce the sleep disturbance scale (P = 0.050). The cost-effectiveness analysis showed that the acceptability curve for a laparoscopic distal pancreatectomy had a higher probability of being more cost-effective than an open distal pancreatectomy when a willingness to pay above 5400 Euros/quality-adjusted life years (QALY) was accepted.ConclusionDespite the limitations of the study, laparoscopic distal pancreatectomy can be considered not only safe and feasible but also permits a better quality of life and is acceptable in terms of cost-effectiveness to Italian and European health care services.

Pancreatic resection in patients 80 years or older: a meta-analysis and systematic review.

Objective The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older. Methods A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay. Results Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P < 0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P < 0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008). Conclusions Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older.

Assessment of Complications According to the Clavien-Dindo Classification After Distal Pancreatectomy

CONTEXT The absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome. PATIENTS Sixty-one patients undergoing distal pancreatectomy. MAIN OUTCOME MEASURES The complications were classified according to the Clavien-Dindo classification; each grade was evaluated regarding the length of the postoperative stay and was compared to the most important complications. RESULTS Thirty (49.2%) patients had no complications; out of the thirty-one (50.8%) patients with complications, 9 (14.5%) had grade I, 15 (24.6%) had grade II, 6 (9.8%) had grade III, and 1 (1.6%) had grade IV. There were no postoperative deaths (grade V). A progressive increase in the length of hospitalization from patients with no complications to those having grade IV (P < 0.001) was noted. Postoperative pancreatic fistula and postpancreatectomy hemorrhage rates did not significantly increase from Clavien-Dindo grade I to grade IV (P = 0.118 and P = 0.226, respectively). The severity of a postpancreatectomy hemorrhage, instead, was positively related to the grade of the Clavien-Dindo classification (P = 0.049) while postoperative pancreatic fistula resulted near the significant value (P = 0.058). CONCLUSIONS The Clavien-Dindo classification is a simple way of reporting all complications following distal pancreatectomy. It allows us to distinguish a normal postoperative course from any deviation and the severity of complications and it may be useful for comparing postoperative morbidity between different pancreatic centers.

Pancreatic Metastasis From Renal Cell Carcinoma

Background Pancreatic metastases from renal cell carcinoma are uncommon. Methods Retrospective study of 8 patients with a diagnosis of pancreatic metastasis from renal cell carcinoma observed in our Institute. Results Patients were 6 (75%) males and 2 (25%) females. Mean age was 65.3 years. In 5 patients (57.1%), symptoms were present. The median interval of onset from nephrectomy was 10 years. No cases of synchronous pancreatic metastases were observed. Surgical resection was performed in 7 (87.5%) patients. At pathological examination, solitary metastases were identified in 5 patients (71.4%). No post-operative mortality was observed; the morbidity rate was 42.8%. In the group of patients who underwent pancreatic resection, median overall survival was 43.0 months (range 12.9–74.5), median disease-free survival was 23.6 months (range 9.9–74.5). Conclusions Pancreatic metastasis from renal cell carcinoma typically occurs after a long period from the initial nephrectomy, and seems to be related to a good prognosis.

Interventional Radiology Procedures after Pancreatic Resections for Pancreatic and Periampullary Diseases

CONTEXT The use of interventional radiology has increased as the first-line management of complications after pancreatic resections. METHODS Patients in whom interventional radiology was performed were compared with those in whom interventional radiology was not performed as regards type of pancreatic resection, diagnosis, postoperative mortality and morbidity, postoperative pancreatic fistula postpancreatectomy haemorrhage, bile leakage, reoperation rate and length of hospital stay. Our aim was to evaluate the usefulness of interventional radiology in the treatment of complications after pancreatic resection. RESULTS One hundred and eighty-two (62.8%) out of 290 patients experienced postoperative complications. Interventional radiology procedures were performed in 37 cases (20.3%): percutaneous drainage in 28, transhepatic biliary drainage in 8 and arterial embolisation in 3 cases. Technical success was obtained in all cases and clinical success in 75.7%. Reoperation was avoided in 86.5%. In patients with major complications, clinically relevant postoperative pancreatic fistula and bile leaks as well as those with late postpancreatectomy haemorrhage (P=0.030) and patients with postpancreatectomy haemorrhage grade C (P=0.029), interventional radiology was used (P<0.001, P<0.001 and P=0.009, respectively) significantly more frequently than in the remaining patients. The reoperation and mortality rates were similar in the two groups (P=0.885 and P=0.100, respectively) while patients treated with interventional radiology procedures had a significant longer length of hospital stay than those in the non-interventional radiology group (37.5 ± 23.4 vs. 18.7 ± 11.7 days; P<0.001). CONCLUSIONS Interventional radiology procedures were useful, especially for patients with postoperative pancreatic fistulas and bile leaks in whom reoperation was very often avoided.

SNP-Array High Resolution Cytogenetic Analysis of Resectable and Advanced Pancreatic Cancer

Context Pancreatic cancer (PC) is the fourth leading cause of cancer deaths. The molecular mechanisms involved in the high tumorigenicity of PC are not yet well-known. Methods Pancreatic tumor samples from 14 patients were collected by ultrasound-guided biopsy and used for DNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Results Nine out of 14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations (CNA) per patient, while 5 patients did not show any copy number gain or loss. Deletions outnumbered amplifications by more than 2 folds. The chromosomes showing more copy number gains were chromosomes 12, 18, 19, while chromosomes 6, 9, 17 and 18 were most frequently deleted. In particular, deletions on 9p21 encompassed CDKN2A and 2B tumor suppressor genes, that on chromosome 18q21 overlapped with SMAD4, the one on chromosome 6p21 included RUNX2, while TP53 and MAP2K4 were the target genes deleted on chromosome 17p13. Amplified regions on chromosome 12p12 encompassed KRAS and ETV6 genes, the one on chromosome 18q11 overlapped with GATA6, while that on 19q13 included AKT2. We observed that the number of alterations correlates with the clinical course, and in particular that patients with none to few alterations (≤6) showed a median time to disease progression and a median overall survival significantly longer than those having a high number of CNA (>6), with a time to disease progression of 13.7 vs . 4.1 months (P=0.015) and an overall survival of 14.6 vs . 4.8 months (P=0.035). Conclusions High resolution cytogenetic analysis by SNP-array has the potential to uncover the genetic alterations carried by pancreatic tumors, and find new markers related to patient prognosis.

Natural History of Branch-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Case Report

CONTEXT The natural history of incidental branch-duct intraductal papillary mucinous neoplasm of the pancreas is still unknown. CASE REPORT The case of a 74-year-old man who had been diagnosed 14 years previously with an incidental branch-duct intraductal papillary mucinous neoplasm of the pancreatic head, 30 mm in size, without mural nodules and dilatation of the main pancreatic duct is herein reported. After an exploratory laparotomy at the time of diagnosis (when he was 60 year-old), the patient was enrolled in a surveillance program. Fourteen years after the diagnosis, the cystic lesion showed an increase in size, Wirsung duct dilatation and the presence of several mural nodules. A total pancreatectomy was performed and a diagnosis of mixed-intraductal papillary mucinous neoplasm diffused throughout the entire pancreas with high grade dysplasia, and a micro-invasive carcinoma (<1 mm) of the pancreatic head was reached. CONCLUSION The present case confirmed that the natural history of branch-duct intraductal papillary mucinous neoplasms is unpredictable. Thus, an appropriate surveillance program is required for prompt identification of the signs predictive of a malignant transformation of branch-duct intraductal papillary mucinous neoplasms. In high-volume centers, surgery should seriously be considered in young patients who are fit for surgery.

The Usefulness of a Multidisciplinary Team Approach in Decision Making For Pancreatic Serous Cystic Neoplasms

CONTEXT Serous cystic neoplasms of the pancreas are regarded as benign entities with rare malignant potential and are frequently resected. OBJECTIVE The purpose of the study was to evaluate the usefulness of a multidisciplinary team (MDT) approach in decision making regarding the diagnosis and management of pancreatic serous cystic neoplasms. METHODS A retrospective study of a prospective database involving 43 patients with serous cystic neoplasms was carried out. Patients who underwent multidisciplinary team evaluation (Group 1) were compared with patients who did not (Group 2) as regards demographic, clinical, radiological, surgical and pathological data. Uni-multivariate analyses were carried out. RESULTS Uni-multivariate analysis showed that a multidisciplinary team approach was significantly related to the type of management, suggesting that MDT evaluation independently reduced the odds of surgery (odds ratio (OR) 0.1; 95% confidence interval (CI) 0.02-0.8; P=0.027). Age, second level imaging techniques, latero-lateral diameter, cranio-caudal diameter and Wirsung duct size differed between the two groups; however, the differences were not statistically significant. CONCLUSIONS A multidisciplinary team approach seems to be useful in proper decision making regarding the diagnosis and management of pancreatic serous cystic neoplasms.

Serum MALDI Profiling for Pancreatic Ductal Adenocarcinoma Biomarkers Discovery: A Pilot Study

Context The available biomarkers for diagnosing pancreatic cancer, like CA 19-9, lack in sensitivity and specificity for an early detection requiring additional efforts to better understand the molecular basis of this pathology and to find novel strategies for a more accurate patient’s screening. Recent advances in quantitative proteomics based on non-invasive approaches have stimulated their clinical applications founded on the analysis of biological fluids like serum. Objective To detect substances able to differentiate pancreatic cancer patients from healthy subjects. Methods Ten sera from histologically proven pancreatic ductal adenocarcinoma patients and 10 from healthy controls comparable for sex and age were analyzed in order to evaluate the small proteins and peptides which could discriminate the two classes. In order to reduce the dynamic range, the high abundant protein components of serum were removed and the MALDI profiling was adopted for the detection of differentially changed species possibly related to the tumor onset. After acquisition, spectra were processed by ClinProTools for statistics (Wilcoxon test P 0.800). Results: MALDI profiling allowed to detect 82 peaks in the acquisition range of 1.5-35 kDa which underwent statistical analysis. The comparison between pathological and control samples revealed a high discrimination power as indicated by the presence of 35 significantly changed peaks (10 over- and 25 under-expressed in cancer) with AUC not lower than 0.872. In addition, several peaks were found strongly represented exclusively in one of the classes suggesting the presence of proteins and peptides which characterize one of the two states, only. Conclusions These preliminary results suggest the potentiality of this approach to discriminate pancreatic cancer patients and controls. The next step will consist on their validation, by increasing the number of analyzed samples, and identification of molecules characterizing the changed peaks associating them to their histological pattern.