Abdominal neoplastic manifestations of neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary tumor syndrome, with a wide clinicopathologic spectrum. It is defined by characteristic central nervous system, cutaneous and osseous manifestations, and by mutations in the NF1 gene, which is involved in proliferation via p21, RAS, and MAP kinase pathways. Up to 25% of NF1 patients develop intra-abdominal neoplastic manifestations including neurogenic (commonly plexiform neurofibromas and malignant peripheral nerve sheath tumors), interstitial cells of Cajal (hyperplasia, gastrointestinal stromal tumors), neuroendocrine, and embryonal tumors (rhabdomyosarcoma). Nonspecific symptoms, multifocal disease, or coexistence of 2 or more tumor types make patients challenging to diagnose and manage. Screening for intra-abdominal tumors in NF1 patients remains controversial, and currently no guidelines are established. Management decisions are complex and often informed by single-center experiences or case studies in the literature, though the field is rapidly evolving. Thus, NF1 patients should be followed in specialist centers familiar with their wide spectrum of pathology and with multidisciplinary care including specialized pathology and radiology. This review will (1) provide a contemporaneous synthesis of the literature and our multi-institutional clinical experiences with intra-abdominal neoplasms in NF1 patients, (2) present a classification framework for this heterogeneous group of disorders, and (3) outline approaches to screening, surveillance, diagnosis, and management.

Is farnesyltransferase inhibitor effective as adjuvant or neoadjuvant therapy in orthotopic implantation of hamster pancreatic cancer

14153 Background: p21-Ras participates in signalling events from membrane tyrosine kinase receptors and a variety of intracellular biochemical pathways to downstream therapeutic strategy.Farnesyl transferase inhibitors (FTI) block the main post-translational plasma membrane and subsequent activation of downstream effector.A curative resection model in Syrian golden hamsters has been developed previously. Aim: To evaluate the effectiveness of FTI as adjuvant or neoadjuvant therapy in hamster experimental pancreatic cancer model. Materials and Methods: HaPT-1,a cell line derived from nitrosamine induced pancreatic cancer was used in these experiments.MTT and MTT agarose were performed.Subcutaneous implanted tumor was resected in exponential phase and tissue was implanted into the pancreas.At Day 7 or Day 14, partial pancreatectomy and splenectomy were performed.Hamsters were divided in 7 groups:1.Positive control (PC,n=5),2.Only FTI (FT,n=5),3.Neodjuvant therapy after surgical resection at Day 7 (NT-R7,n=10),4.Adjuvant therapy after resection at Day 7 (AT-S7,n=10),5.Neoadjuvant therapy after resection at Day 7 (NT-S14,n=10),6.Adjuvant therapy after resection at Day 14 (AT-S14,n=10), and 7.Only surgery at Day 14 (SR,n=5).FTI was administered for one week. In FT and NT groups, drug was administered 3 days after orthotopic implantation.Body weight and side effects were recorded.Fourteen days after the surgical resection, sacrifice was done.Four animals of each group were left to study the survival.After 180 days, living hamsters were sacrificed. Resected and necropsied specimens were sent to histopathological analysis. Results: Successful rate of implantation was 100%.PC,FT,NT-S7,AT-S7,NT-S14,AT-S14,and SR survived in average 82,103,119,134,123,132,and 139 days.Two hamsters of AT-S7 (20%),two of AT-S14 (20%),and two of SR (40%) were alive until 180 days.Intra operatory bleeding was higher in NT groups.Loss of body weight was present in all FTI treated groups. Conclusions: Farnesyltransferase inhibitor showed not to be effective in the curative treatment of orthotopically implanted tumors. It may be used to increase the survival time as adjuvant therapy. No significant financial relationships to disclose.