Giuseppe Mascetta

Pancreatic Fistula Rate after Pancreatic Resection

Background: Pancreatic fistula (PF) is still regarded as a serious complication both in terms of frequency and sequelae. The incidence varies greatly in different reports because of the different definitions used. The aim of this study was to compare several definitions of PF encountered in the current literature and to demonstrate that the PF rate in the same group of patients treated in a high volume center is dependent upon the definition applied. Methods: A Medline search of the last 10 years was performed as regards the definition of PF. A score was assigned to the reproducible definitions based upon two basic parameters: daily output (cm3) and duration of the fistula represented by the number of days between the postoperative day of onset and the duration of the complication. Four definitions were formulated and were then applied to a group of 242 patients that underwent pancreatic head or intermediate resections with pancreatico-jejunal anastomosis in our Pancreatic Unit between November 1996 and December 2000. Statistical analysis was carried out using the Yates correct χ2 test with statistical significance set at p < 0.05. Results: Among 26 different definitions identified, 14 were found suitable for the applied score. We formulated four final definitions summarizing the current concepts of PF. The incidence of PF ranged between 9.9 and 28.5% according to the different definitions applied with highly statistical differences between them. Conclusions: The PF rate after pancreatic resections is strictly dependent upon the definition used. An overall general agreement for an internationally accepted definition is urgently needed to correctly compare different experiences.

Management of Complications after Pancreaticoduodenectomy in a High Volume Centre: Results on 150 Consecutive Patients

Pancreaticoduodenectomy (PD) is still a difficult procedure with significant morbidity. We report 150 consecutive PDs performed during a 3-year period. All the cases have been prospectively evaluated with regard to the surgical outcome. Mortality in this series was 3/150 (2%) with a re-operation rate of 5/150 (3.3%); surgical complications were experienced in 57/150 (38%). The most frequent complications were collections in 25/150 (16.6%) and pancreatic fistulas in 16/150 (10.7%). The majority of these complications were conservatively managed: only one abscess and one fistula due to an anastomotic dehiscence required re-operation. The complication most responsible for mortality was haemorrhage secondary to arterial pseudoaneurysms in patients with severe post-operative pancreatitis. The continued high morbidity of PDs is compensated by the ability to treat complications non-operatively, resulting in a surgical risk that should now be considered medium to low in high volume centres.

Pancreatic insufficiency after different resections for benign tumours

Pancreatic resections for benign diseases may lead to long‐term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long‐term results after different pancreatic resections for benign disease.

Beneficial Effects of Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in Rat Experimental Colitis

Background and Aims: Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix composition playing a major role in the inflammatory response. In the present study we evaluated the ability of the MMP inhibitor Batimastat (BB-94) to modify the course of experimental colitis induced in the rat by trinitrobenzensulfonic acid (TNB). Methods: Colitis was induced in 40 rats by intracolonic administration of TNB. Animals were divided into four groups of ten rats each: group 1 received only intracolonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB+10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was administered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals were killed after seven days; segments of colon were removed and used for histological score of inflammation and myeloperoxidase (MPO) activity. Results: Rats receiving only intracolonic 0.9% saline showed no evidence of colitis. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-treated rats) exhibited a high inflammation score (12.4) and MPO activity (0.715 U/mg). Conversely, BB-94-treated rats showed, compared to the TNB group, a significantly lower inflammation score and MPO activity in a dose-dependent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.05 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 vs. TNB); group 4: inflammatory score 5.0, MPO activity 0.256 (p < 0.01 vs. TNB). Conclusions: Treatment with BB-94 has dose-dependent beneficial effects on the inflammatory alterations in rat experimental colitis. Thus, the inhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation.

Novel functional PI 3-kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines

New efforts in cancer therapy are being focused at various levels of signaling pathways. With phosphoinositide 3‐kinase (PI3‐K) potentially being necessary for a range of cancer‐related functions, we have investigated the influence of selected inositol tristo hexakisphosphates on cell growth and tumorigenicity. We show that micromolar concentrations of inositol 1,3,4,5,6‐pentakisphosphate and inositol 1,4,5,6‐tetra‐kisphosphate [Ins(1,4,5,6)P4] inhibit IGF‐1‐induced [3H]‐thymidine incorporation in human breast cancer (MCF‐7) cells and the ability to grow in liquid medium and form colonies in agarose semisolid medium by small cell lung cancer (SCLC) cells, a human cancer cell line containing a constitutively active PI3‐K. In an ovarian cancer cell line that also contains a constitutively active PI3‐K (SKOV‐3 cells), Ins(1,4,5,6)P4 again inhibited liquid medium growth. Furthermore, when applied extracellularly, inositol 1,3,4,5‐tetrakisphosphate was shown indeed to enter SCLC cells. These effects appeared specifically related to PH domains known to bind to phosphatidylinositol 3,4‐bisphosphate [PtdIns(3,4)P2] and phosphatidylinositol 3,4,5‐trisphosphate [PtdIns(3,4,5)P3], indicating involvement of the PI3‐K downstream target protein kinase B (PKB/Akt). This was further supported by inhibition of PKB/Akt PH domain membrane targeting in COS‐7 cells by Ins(1,4,5,6)P4. Thus, we propose that specific inositol polyphosphates inhibit PI3‐K by competing with PtdIns(3,4,5)P3‐binding PH domains and that this occurs mainly at the level of the downstream PI3‐K target, PKB/Akt.—Razzini, G., Berrie, C. P., Vignati, S., Broggini, M., Mascetta, G., Brancaccio, A., Falasca, M. Novel functional PI 3‐kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines. FASEB J. 14, 1179–1187 (2000)

Long-term results of Frey's procedure for chronic pancreatitis: a longitudinal prospective study on 40 patients.

Only limited prospective data are available regarding the long-term outcome of local resection of the pancreatic head in combination with longitudinal pancreaticojejunostomy in patients with chronic pancreatitis. From 1997 to 2001, 40 patients affected by chronic pancreatitis were subjected to the Frey’s procedure. Preoperative selection criteria included confirmed diagnosis of chronic pancreatitis, dilation of Wirsung’s duct to a diameter greater than 6 mm, and the absence of obstructive chronic pancreatitis secondary to fibrotic stenosis at the pancreatic body or tail. Preoperative pain was present in 38 cases (95%), and follow-up was performed in all patients at least once Yearly up to 2003 (median 60 months, inter percentile range 20.1-79.6). Postoperative morbidity occurred in three cases (7.5%). The percentage of pain-free patients was 94.7%, 93.7%, 87.5%, and 90% at 1, 2, 3, and 4/5 Years after surgical operation, respectively. After surgery, three patients developed diabetes. Both the body mass index and quality of life showed statistically significant improvements at all follow-up intervals. Whenever surgery is indicated, the short-term and long-term outcomes confirm that Frey’s procedure is an appropriate means of management for patients with chronic pancreatitis in the absence of doubts of neoplasia and/or distal ductal obstruction.

Substance P and neprilysin in chronic pancreatitis.

Background/Aims: We aimed to analyze substance P (SP) and neprilysin (NEP), the membrane metallopeptidase that degrades SP, in chronic pancreatitis (CP). Methods: SP and NEP mRNA levels were analyzed by qRT-PCR in tissue samples from 30 patients with CP and 8 organ donors. In addition, SP serum levels were determined before and after surgery in the same patients, by means of a competitive ELISA assay. Genetic and epigenetic analyses of the NEP gene were also performed. Results: SP mRNA expression levels were higher in CP tissues compared to controls (p = 0.0152), while NEP mRNA showed no significant differences between CP and healthy subjects (p = 0.2102). In CP patients, SP serum levels correlated with those in tissue, and after surgical resection SP serum levels were reduced compared to the preoperative values. Failure of NEP to overexpress in CP tissues was associated with significant miR-128a overexpression (p = 0.02), rather than with mutations in the NEP coding region or the presence of hypermethylation sites in the NEP promoter region. Conclusion: Tissue and serum levels of SP were increased in CP, while NEP levels remained unaltered. In an SP/NEP-mediated pathway, it would appear that NEP fails to provide adequate surveillance of SP levels. Failure of NEP to overexpress could be associated with miRNA regulation.

Pancreatic Frozen Section in Distal Pancreatectomy: Verona Experience with Harmonic Focus®

Context Pancreatic head resection is performed with low mortality, but morbidity remains high. Extensive preparation, long operating times, intraoperative blood loss and the need for blood transfusions are risk factors for post-operative morbidity. Many authors demonstrated that the use of an ultrasonic dissection device in distal pancreatectomy might significantly reduce operating time, intraoperative blood loss and the need for blood transfusions. Intraoperative frozen section analysis has traditionally played an important role in the surgical management of pancreatic lesions. Currently limited data exist in the surgical literature regarding the accuracy of frozen section analysis for the purpose of determining resectability and assessing final margin status. No data are available about the feasibility of the frozen section performed with the harmonic scalp. Methods A retrospective review was performed for all patients who underwent open, laparoscopic or robotic distal pancreatic resection for cancer (adenocarcinoma or IPMN, or NET) at our institution from 2010 to 2012. The pancreatic transection was effectuated by scalpel or by harmonic scalpel (Harmonic Focus ® ). Frozen section was performed routinely. Results One-hundred and two distal pancreatic resections were performed in our Institution. In 79 patients the pancreatic transection was effectuated by scalpel and in all cases the final pathological diagnosis coincided with the frozen section. In 22 patients, the pancreatic section was performed using the Harmonic Focus ® . Two frozen sections resulted negative for neoplastic cell research but were positive at definitive examination. Conclusion Use of an ultrasonic dissection device (Harmonic Focus ® ) in distal pancreatectomy is safe and feasible. The electrocution of the harmonic scalp could distort the frozen section examination so, where possible, we suggest performing the frozen section with the scalpel.

Pancreatic Surgery in Patients with Concomitant Liver Cirrhosis: A Single Centre Experience

Context Liver cirrhosis is known to negatively affect the outcome of various types of surgery, but very poor data on the safety of pancreatic surgery in cirrhotic patients are available. As a consequence, a consensus on the operability of this subgroup of patients do not exist, and the fear of complications often results in the decision to avoid surgery. However, pancreatic surgery is presently the only curative option for malignant disease, and an aggressive tumor resection is therefore mandatory whenever possible. Only one published study has investigated the risk of pancreatic surgery in cirrhotic patients, concluding that whereas Child A patients display increased complications but a relatively low mortality, surgery in Child B patients should be avoided. Objective To investigate the outcome of cirrhotic patients who underwent surgery for a pancreatic disease at our institution. Methods Between 2003 and 2010, 53 patient with pancreatic pathology and concomitant liver cirrhosis came to our observation. Among these 17 were addressed to surgery. We retrospectively analyzed data about the clinical-pathological features of these patients, classified them on the basis of the Child score and evaluated the post-operative outcome. Fourteen patients were Child A, 3 Child B; 9 underwent a radical pancreatic resection, 6 a palliative procedure, 2 a laparoscopic abdominal exploration. The main indication for surgery was pancreatic adenocarcinoma (n=11). Results Among the 17 operated patients, 13 had a regular post-operative course (76%), 4 experienced a complication (24%). Only 1 patient (6%) died due to surgery-related complications. The mean post-operative hospital stay was 9.2 days. Significantly, all the Child B patients had a regular post-operative course. Conclusions In our experience, the presence of liver cirrhosis, even Child B cirrhosis, is not an absolute contraindication for pancreatic surgery. A careful preoperative selection and an adequate post-operative care can offer an acceptable clinical outcome even in those patients usually considered not eligible for surgery.

2001: Author Index for abstracts

Babyatsky, M.W. 272 Baffi, M.C. 273 Ball, A.J. 269 Ballinger, A.B. 273 Bantick, S. 254 Barbara, G. 254 Barrachina, M.D. 271 Beckett, E.A.H. 250 Beckmann, C. 254 Bellinger, L.L. 252 Bielanski, W. 270 Bielefeldt, K. 267, 274 Bilski, J. 262 Bischoff, S. 251 Bonaz, B. 274, 275 Bonior, J. 262, 273 Booth, C.E. 267 Bradley, J.M. 249 Brammer, M.J. 254 Brinkman, B. 264 Brodacz, B. 270 Brown, D.R. 271 Browning, K.N. 272 Bruijnzeel, A.W. 277 Brzozowski, T. 261, 270 Bueno, L. 274, 275 Burr, R.L. 276 Burton, D. 264