The significance of Trk receptors in pancreatic cancer.

This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation altered expression of four neuroendocrine genes and whether this resulted in subsequent changes in radiosensitivity. A specific inhibitor of TrkA, B, and C, AstraZeneca 1332, was investigated in vitro and in vivo in combination with radiation. A tissue microarray was constructed from 77 pancreatic ductal adenocarcinoma patients who had undergone neoadjuvant chemoradiation and the Trk receptor, and neurogenic differentiation 1 expression was assessed and correlated with overall survival. A total of 99 genes were identified that were differentially expressed in the chemoradiation patients with neuroendocrine genes and pathways, in particular the neurogenic differentiation 1 and Trk receptor family, being prominent. Fractionated radiation upregulated the expression of neuroendocrine genes, and AstraZeneca 1332 treatment in vitro enhanced radiosensitivity. No added effect of AstraZeneca 1332 was observed in vivo. Trk receptor expression varied between isoforms but did not correlate significantly with clinical outcome. Radiation treatment upregulated neuroendocrine gene expression but the Trk receptor family does not appear to be a promising treatment target.

Gene expression changes associated with the progression of intraductal papillary mucinous neoplasms.

OBJECTIVES: The diagnosis of high-grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low-grade IPMN. The aim of this study was to identify potential markers for the discrimination of high-grade and invasive (HgInv) IPMN from low- and moderate-grade dysplasia IPMN. METHODS: Laser capture microdissection was used to isolate distinct foci of low-grade, moderate-grade, high-grade, and invasive IPMN from paraffin-embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used to compare low- and moderate-grade dysplasia IPMN with HgInv IPMN. RESULTS: Sixty-two genes were identified as showing significant changes in expression (P ≤ 0.05 and a 2-fold cutoff), including up-regulation of 41 in HgInv IPMN. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial-to-mesenchymal transition. In addition, altered signaling in several transforming growth factor ß-related pathways was exhibited in the progression of IPMN to malignancy. CONCLUSIONS: This study identifies a set of genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection.

Phase I study of conformal radiotherapy and concurrent full-dose gemcitabine with erlotinib for unresected pancreatic cancer.

PURPOSE: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. METHODS AND MATERIALS: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. RESULTS: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. CONCLUSION: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Implementing a multidisciplinary open-access clinic at a private practice-based community hospital.

With the acquisition of emerging technologies in the treatment of primary and metastatic hepatic malignancy by interventional radiology, a multidisciplinary tumor board was created by the authors to improve treatment planning for these diseases.

Minimally invasive and standard surgical therapy for complications of pancreatitis and for benign tumors of the pancreas and duodenal papilla.

The treatment of severe pancreatitis and its complications is rapidly evolving because of increasing clinical application of effective, minimally invasive techniques. With ongoing innovations in therapeutic endoscopy, image-guided percutaneous techniques, and minimally invasive surgery, the long-standing traditional management algorithms have recently changed. A multidisciplinary approach is necessary for the treatment of complicated inflammatory diseases of the pancreas and benign periampullary tumors. Surgeons, gastroenterologists, and therapeutic radiologists combine expertise as members of a team to offer their patients improved outcomes and faster recovery.

Endoscopic management of early upper gastrointestinal hemorrhage following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND AND AIMS: Upper gastrointestinal hemorrhage (UGIH) is an infrequent complication (1-3.8%) following laparoscopic Roux-en-Y gastric bypass (LRYGB). The safety and efficacy of endoscopic management of immediate postoperative bleeding is unknown. We sought to determine how frequently UGIH complicates LRYGB and whether endoscopic management is successful in controlling hemorrhage. METHODS: Retrospective chart review of all patients who developed UGIH following LRYGB from November 2001 to July 2005 at a large suburban teaching hospital. RESULTS: Of 933 patients who underwent LRYGB, 30 (3.2%) developed postoperative UGIH. An endoscopic esophagogastroduodenoscopy (EGD) was performed in 27/30 patients (90%). All were found to have bleeding emanating from the gastrojejunostomy (GJ) staple line. Endoscopic intervention was performed in 24/30 (80%) with epinephrine injection and heater probe cautery being used most commonly. Endoscopic therapy was ultimately successful in controlling all hemorrhage, with 5 patients (17%) requiring a second EGD for rebleeding. No patient required surgery to control hemorrhage. One patient aspirated during the endoscopic procedure with subsequent anoxic encephalopathy and died 5 days postoperatively. Twenty-one patients (70%) developed UGIH in the intraoperative or immediate postoperative period (<4 h postoperative). The mean length of stay was significantly longer in these patients (2.84 vs 4.1, P= 0.001). CONCLUSIONS: (a) UGIH complicates LRYGB in a small but significant number of patients. (b) Bleeding usually occurs at the GJ site. (c) EGD is safe and effective in controlling hemorrhage with standard endoscopic techniques. (d) UGIH occurs most commonly in the immediate postoperative period and may be best managed in the operating room with the patient intubated to prevent aspiration.