Alan J. Durkin

Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies

AbstractBackground: There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies. Methods: Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers. Results: Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis. Conclusion: We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.

Financial Status Does Not Predict Weight Loss After Bariatric Surgery

Background: Lower socioeconomic status and poor funding are thought to be associated with suboptimal outcome after bariatric surgery. We undertook this study to determine if funding status is a predictor of outcome in patients undergoing bariatric surgery. Methods: The medical records of 131 consecutive patients who underwent vertical banded gastroplasty (VBG) for clinically severe obesity (BMI >40 kg/m2) were reviewed. Patients were divided into three groups based on insurance status: (1) commercially insured/traditional indemnity programs; (2) entitlement programs (Medicare), and (3) medically indigent (Medicaid or no funding). Data is mean ± SD. Data was analyzed using ANOVA and Student t-test. Results: The three groups had similar preoperative weight. Mean BMI was 39 ± 13, 42 ± 15, 41 ± 11 at 1 year, and 40 ± 13, 43 ± 16, 45 ± 16 at 2 years postoperatively for the Insured, entitlement, and indigent groups, respectively. Conclusion: After standard preoperative evaluation and screening, patients loss weight following VBG independent of insurance status. Source of funding should, therefore, not preclude patients from undergoing bariatric surgery. Patients with limited financial resources can expect similar outcomes as patients with commercial insurance.

Post-Shunt Resource Consumption Favors Small-Diameter Prosthetic H-Graft Portacaval Shunt over TIPS for Patients with Poor Hepatic Reserve

ObjectiveTo define the role of surgical shunting for patients with poor hepatic reserve (Child’s class C) in the era of TIPS. Summary Background DataMost physicians prefer TIPS to surgical shunting for patients with poor hepatic reserve because of anticipated poor long-term survival. MethodsSixty-two patients of Child’s class C with bleeding varices not amenable to endoscopic sclerotherapy or banding were prospectively randomized to undergo TIPS or 8-mm prosthetic H-graft portacaval shunt (HGPCS) from 1993 to 1999. Resource consumption and survival after shunting were determined. ResultsTwenty-nine patients underwent TIPS and 33 underwent HGPCS. After HGPCS, survival at 3 years was favorable but not statistically superior. TIPS was more often associated with shunt stenoses/occlusions, recurrent hemorrhage, shunt revisions, and shunt failure. Long-term follow-up documented that after HGPCS, patients required fewer hospital and ICU days and fewer units of RBCs transfused. After HGPCS, cost of care was less, as was the median cost of care per day of survival. ConclusionsFor Child’s class C patients undergoing HGPCS or TIPS, long-term survival is similar, though favoring HGPCS. Similarly, measures of resource consumption and cost of care following hospital discharge favor HGPCS. HGPCS should be preferentially applied for acceptable patients without access to convenient capable post-shunt care or without definitive plans for imminent transplantation.

Surgical management of early-stage pancreatic cancer.

BACKGROUND Pancreatic cancer remains a difficult disease to treat. Diagnosis at an early stage may allow curative treatment with resection. In the past, the mortality associated with surgical treatment of pancreatic carcinoma was prohibitive but mortality associated with resection is now commensurate with all other major oncologic resections. Thus, the focus of surgical management has shifted to address several issues: the diagnosis and evaluation of patients with suspected pancreatic cancer, the role of preoperative endobiliary stenting, the role of laparoscopy, the extent of resection, the role of adjuvant and neoadjuvant treatment, and the role of specialized centers in treating the disease. METHODS The current literature is reviewed to address these issues and help guide physicians who first encounter patients with suspected pancreatic cancer as well as surgeons who ultimately resect them. Practical evidence-based information to guide the decision-making process is provided. RESULTS Surgical morbidity and mortality have achieved parity with other types of major oncologic resection, and a distinct survival advantage is possible when such therapy is applied early in the disease stage. Issues regarding the use of stents, extent of resection, and pre- vs post-operative chemoradiation therapy are becoming clearer as our collective experience broadens. CONCLUSIONS Surgical treatment of pancreatic cancer should be aggressively pursued given the clearly established survival advantage and relief of symptoms achieved when it is applied appropriately.

An Algorithmic Approach to Breast Reconstruction Using Latissimus Dorsi Myocutaneous Flaps

BACKGROUND Innovative surgical techniques developed by surgical oncologists have changed the landscape of mastectomy defects. Latissimus dorsi myocutaneous flap-based breast reconstruction provides a reliable foundation for breast reconstruction. The purpose of this study was to evaluate differential skin island designs with latissimus dorsi myocutaneous flap breast reconstruction, and to develop an algorithmic approach to breast reconstruction that is applicable to a broad spectrum of mastectomy defects. METHODS In this study, the authors retrospectively reviewed data of patients who underwent latissimus dorsi myocutaneous flap reconstruction following unilateral or bilateral mastectomies between February of 2001 and April of 2005. Patients were selected to undergo reconstruction under the following circumstances: (1) previously irradiated tissue, (2) body mass index greater than 30, (3) current tobacco use, (4) previous abdominopelvic surgery, and (5) patient preference. Patients were divided into three groups based on defect present: intact inframammary fold with skin deficit, intact inframammary fold without skin deficit, and absent inframammary fold with or without skin deficit. Differential skin island design was customized to the presenting mastectomy defect to optimize results and minimize donor-site scaring. RESULTS Fifty-four patients underwent 64 latissimus dorsi myocutaneous flap reconstructions. Aesthetic outcomes and donor-site scar placement differed between groups. CONCLUSIONS The authors have developed an algorithmic approach to latissimus dorsi myocutaneous flap breast reconstruction. Through critical evaluation of mastectomy defects, reconstructive breast surgeons can tailor skin island orientation, minimize donor-site scarring, enhance cosmetic outcomes, and provide a durable and natural aesthetic outcome in breast reconstruction with the latissimus dorsi myocutaneous flap.

Amlodipine Besylate Induced Acute Interstitial Nephritis

Adverse effects of amlodipine besylate, a widely used antihypertensive medication, include peripheral edema, flushing, headache, pruritus, and rash. An adverse renal effect attributable to the medication has hitherto not been reported in the literature. We herein report a case of amlodipine besylate induced acute interstitial nephritis.

Laparoscopic resection of extraadrenal pheochromocytoma.

Laparoscopic resection is now considered standard of care for most pheochromocytomas arising from the adrenal glands. Extraadrenal pheochromocytoma presents unique challenges for laparoscopic resection. Considerations include preoperative preparation, port placement, exposure, anesthetic management, hemostasis and protection of surrounding normal anatomic structures. This multimedia article describes and illustrates the diagnosis, surgical approach and follow up of a 25 year old patient with extraadrenal pheochromocytoma and no family history. The presentation addresses all aspects of the management of this unique clinical entity and provides an excellent review for the surgeon considering laparoscopic approach to any retroperitoneal tumor occurring in this location.

EGF receptor (EGFR) antagonism inhibits pancreatic cancer (PCA) growth in-vitro and in-vivo

Abstract Introduction: Pancreatic tumors have been shown to overexpress EGFR. The purpose of this study was to determine whether EGFR inhibition is a plausible therapeutic strategy in PCA and to compare its efficacy to matrix metalloproteinase inhibition (MMPI) alone or in combination with EFGR blockade. Methods: HPAC, a moderately differentiated cell line, was evaluated for the presence of EGFR using rtPCR and immunohistochemistry. Cells were grown in the presence of 50uM or 100uM of erlotinib, a small molecule tyrosine kinase inhibitor specific for EGFR and proliferation was evaluated by MTT assay for 72hrs. 86 nude mice underwent orthotopic implantation of HPAC and were randomized into four groups: 1) Control 2) MMPI (400ng/ml i.p. QOD) 3) Erlotinib (100mg/kg i.p. QD) or 4) MMPI + Erlotinib. MTT data was evaluated with a paired Student’s t-test. Survival data was analyzed by the Kaplan-Meier method. Results: HPAC showed high expression of the EGFR gene and gene product. In vitro growth inhibition with erlotinib was significant at 48 and 72hrs. In vivo, each treatment group showed a significant survival advantage vs control, with erlotinib showing markedly improved survival as compared to all other groups. Combined treatment with MMPI and Erlotonib was not as efficaceous as either agent alone. Mice treated with erlotinib showed reduced tumor implantation, size, weight, metastases and jaundice compared to control or BB-94. Conclusions: EGFR antagonism is a plausible therapy for treatment of PCA, and is superior to MMPI alone or in combination with erlotinib.