Pathological and molecular evaluation of pancreatic neoplasms

Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives

Surgical management of giant Brunner's gland hamartoma: case report and literature review

Brunner's gland hamartomas (BGH) are uncommon benign tumors of the duodenum forming mature Brunner's glands. We report here an unusual case of a giant BGH that was not amenable to endoscopic or surgical local resection thus requiring a pancreaticoduodenectomy for extirpation. The relevant literature is discussed

Building A Winning NFL Roster: Best Practices For Sustained Success

The purpose of this capstone is to identify and analyze the factors that contribute to team success in the National Football League through a review of relevant literature, a survey of league personnel, and firsthand experience as a football administrator. This project first studies quantitative data regarding player acquisition, specifically the data behind the NFL entry draft. Next, the current literature regarding off the field processes such as leadership, organizational culture and engagement were reviewed and finally, a two-step Delphi method survey was distributed to a panel of current league professionals. This paper aims to find the most efficient and effective way for teams to acquire players and several ways to optimize that talent based on the best practices researched in organizational culture and leadership

Comparison of EUS-guided tissue acquisition using two different 19-gauge core biopsy needles: a multicenter, prospective, randomized, and blinded study

BACKGROUND AND STUDY AIMS: The optimal core biopsy needle for endoscopic ultrasound (EUS) is unknown. The principle aim of this study is to compare outcomes of EUS-fine-needle biopsy (EUS-FNB) with a new 19-gauge EUS histology needle (ProCore, Cook Medical Inc., Winston-Salem, North Carolina, United States) to a conventional 19-gauge Tru-Cut biopsy (EUS-TCB) needle (19G, Quick-Core, Cook Medical Inc.). PATIENTS AND METHODS: Patients referred for EUS who require possible histologic biopsy were prospectively randomized to EUS-FNB or EUS-TCB. With the initial needle, ≤ 3 biopsies were obtained until either technical failure or an adequate core was obtained. Patients with suspected inadequate biopsies were crossed over to the other needle and similarly ≤ 3 passes were obtained until adequate cores or technical failure occurred. Technical success, diagnostic histology, accuracy and complication rates were evaluated. RESULTS: Eighty-five patients (mean 58 years; 43 male) were randomized to FNB (n = 44) and TCB (n = 41) with seven patients excluded. Procedure indication, biopsy site, mass size, number of passes, puncture site, overall technical success and adverse events were similar between the two groups. FNB specimens had a higher prevalence of diagnostic histology (85 % vs. 57 %; P = 0.006), accuracy (88 % vs. 62 %; P = 0.02), mean total length (19.4 vs. 4.3 mm; P = 0.001), mean complete portal triads from liver biopsies (10.4 vs. 1.3; P = 0.0004) and required fewer crossover biopsies compared to those of TCB (2 % vs. 65 %; P = 0.0001). Overall technical success and complication rates were comparable. CONCLUSION: EUS-FNB using a 19-gauge FNB needle is superior to 19-gauge EUS-TCB needle

Resected serous cystic neoplasms of the pancreas: Locally aggressive behavior as a predictor of malignant disease? A review of 158 patients with recommendations for treatment.

Background: Serous cystic neoplasms of the pancreas are regarded as a benign entity with rare malignant potential. Surgical resection is generally considered curative. Objective: To perform the largest single institution review of patients who underwent surgical resection for serous cystic neoplasms of the pancreas in the hopes of guiding future management. Methods: Between June 1988 and January 2005, 158 patients with serous cystic neoplasms of the pancreas underwent surgical resection. A retrospective analysis was performed. Univariate and multivariate models were used to determine factors influencing perioperative morbidity and mortality. Major complications were defined as pancreatic fistula or anastomotic leak, postoperative bleed, retained operative material, or death. Minor complications were defined as wound infection, postoperative obstruction/ileus requiring TPN, delayed gastric emptying, arrhythmia, or other infection. Results: The mean age of the patients was 62.1 years, with 75% being female. The majority of patients were symptomatic at presentation (63%), with abdominal pain as the most common symptom. Of the 158 patients, 75 underwent distal pancreatectomy, 65 underwent pancreaticoduodenectomy, 9 underwent central pancreatectomy, 5 underwent local resection or enucleation, and 4 underwent total pancreatectomy. Mean tumor diameter was 5.1 cm. Mean operative time was 277.5 minutes. Mean postoperative length of hospital stay was 11 days. One patient was diagnosed at presentation with serous cystadenocarcinoma. The remaining 157 patients were initially diagnosed with benign serous cystadenoma. One of three patients with locally aggressive benign disease later presented with metastatic disease. Resection margins for all 158 patients were negative for tumor, and only 1 (0.6%) showed lymph node involvement. There was one intraoperative death. The incidence of major perioperative complications was 18%, while the incidence of minor complications was 33%. Men were significantly more likely to experience minor perioperative complications (OR = 3.74, P = .008), while patients greater than 65 years showed a trend toward fewer major complications (OR = 0.36, P = .09). Conclusions: Serous cystic neoplasms of the pancreas which are surgically resected are typically seen in asymptomatic women, as 5 cm neoplasms which are predominantly benign. Most are resected via either a left or right sided pancreatectomy with low mortality risk, but with notable major or minor morbidity. Cystadenocarcinoma is a rare finding on initial resection of serous cystic neoplasms. However, initial pathology specimens exhibiting benign but locally aggressive neoplasia may indicate an increased likelihood of recurrence or metachronous metastasis

Conductance spectra of (Nb, Pb, In)/NbP -- superconductor/Weyl semimetal junctions

The possibility of inducing superconductivity in type-I Weyl semimetal through coupling its surface to a superconductor was investigated. A single crystal of NbP, grown by chemical vapor transport method, was carefully characterized by XRD, EDX, SEM, ARPES techniques and by electron transport measurements. The mobility spectrum of the carriers was determined. For the studies of interface transmission, the (001) surface of the crystal was covered by several hundred nm thick metallic layers of either Pb, or Nb, or In. DC current-voltage characteristics and AC differential conductance through the interfaces as a function of the DC bias were investigated. When the metals become superconducting, all three types of junctions show conductance increase, pointing out the Andreev reflection as a prevalent contribution to the subgap conductance. In the case of Pb-NbP and Nb-NbP junctions, the effect is satisfactorily described by modified Blonder-Tinkham-Klapwijk model. The absolute value of the conductance is much smaller than that for the bulk crystal, indicating that the transmission occurs through only a small part of the contact area. An opposite situation occurs in In-NbP junction, where the conductance at the peak reaches the bulk value indicating that almost whole contact area is transmitting and, additionally, a superconducting proximity phase is formed in the material. We interpret this as a result of indium diffusion into NbP, where the metal atoms penetrate the surface barrier and form very transparent superconductor-Weyl semimetal contact inside. However, further diffusion occurring already at room temperature leads to degradation of the effect, so it is observed only in the pristine structures. Despite of this, our observation directly demonstrates possibility of inducing superconductivity in a type-I Weyl semimetal.Comment: Accepted for Phys. Rev. B. 13 pages, 12 figures. Second version with major revisions. The title was changed. One author R. Jakiela added. New inset to Fig. 8(A). New fits in Fig. 8 (B) and Fig. 10 (B). Added figures 12 (C)-(E). Added Fig. 12 (F) with SIMS data. Rewritten chapters III-C-2 and III-C-3. Reference no. 38 removed, 11 new references: 9, 21, 22, 40-44, 46-49 were adde

Copy-Number Variants in Patients with a Strong Family History of Pancreatic Cancer

Copy-number variants such as germ-line deletions and amplifications are associated with inherited genetic disorders including familial cancer. The gene or genes responsible for the majority of familial clustering of pancreatic cancer have not been identified. We used representational oligonucleotide microarray analysis (ROMA) to characterize germ-line copy number variants in 60 cancer patients from 57 familial pancreatic cancer kindreds. Fifty-seven of the 60 patients had pancreatic cancer and three had nonpancreatic cancers (breast, ovary, ovary). A familial pancreatic cancer kindred was defined as a kindred in which at least two first-degree relatives have been diagnosed with pancreatic cancer. Copy-number variants identified in 607 individuals without pancreatic cancer were excluded from further analysis. A total of 56 unique genomic regions with copy-number variants not present in controls were identified, including 31 amplifications and 25 deletions. Two deleted regions were observed in two different patients, and one in three patients. The germ-line amplifications had a mean size of 662 Kb, a median size of 379 Kb (range 8.2 Kb to 2.5 Mb) and included 425 known genes. Examples of genes included in the germ-line amplifications include the MAFK, JunD and BIRC6 genes. The germ-line deletions had a mean size of 375Kb, a median size 151 Kb (range 0.4 Kb to 2.3 Mb) and included 81 known genes. In multivariate analysis controlling for region size, deletions were 90% less likely to involve a gene than were duplications (p < 0.01). Examples of genes included in the germ-line deletions include the FHIT, PDZRN3 and ANKRD3 genes. Selected deletions and amplifications were confirmed using real-time PCR, including a germ-line amplification on chromosome 19. These genetic copy-number variants define potential candidate loci for the familial pancreatic cancer gene