Eugene P. Ceppa

Calcitonin receptor‐like receptor (CLR), receptor activity‐modifying protein 1 (RAMP1), and calcitonin gene‐related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution

Calcitonin gene‐related peptide (CGRP) is a key mediator in primary headaches including migraine. Animal models of meningeal nociception demonstrate both peripheral and central CGRP effects; however, the target structures remain unclear. To study the distribution of CGRP receptors in the rat trigeminovascular system we used antibodies recognizing two components of the CGRP receptor, the calcitonin receptor‐like receptor (CLR) and the receptor activity‐modifying protein 1 (RAMP1). In the cranial dura mater, CLR and RAMP1 immunoreactivity (‐ir) was found within arterial blood vessels, mononuclear cells, and Schwann cells, but not sensory axons. In the trigeminal ganglion, besides Schwann and satellite cells, CLR‐ and RAMP1‐ir was found in subpopulations of CGRP‐ir neurons where colocalization of CGRP‐ and RAMP1‐ir was very rare (≈0.6%). CLR‐ and RAMP1‐ir was present on central, but not peripheral, axons. In the spinal trigeminal nucleus, CLR‐ and RAMP1‐ir was localized to “glomerular structures,” partly colocalized with CGRP‐ir. However, CLR‐ and RAMP1‐ir was lacking in central glia and neuronal cell bodies. We conclude that CGRP receptors are associated with structural targets of known CGRP effects (vasodilation, mast cell degranulation) and targets of unknown function (Schwann cells). In the spinal trigeminal nucleus, CGRP receptors are probably located on neuronal processes, including primary afferent endings, suggesting involvement in presynaptic regulation of nociceptive transmission. Thus, in the trigeminovascular system CGRP receptor localization suggests multiple targets for CGRP in the pathogenesis of primary headaches. J. Comp. Neurol. 507:1277–1299, 2008.

Effectiveness of Laparoscopic Computer Simulator Versus Usage of Box Trainer for Endoscopic Surgery Training of Novices

OBJECTIVEnTeaching of laparoscopic skills is a challenge in surgical training programs. Because of the highly technical nature and the steep learning curve, students and residents must learn laparoscopic skills before performing them in the operating room. To improve efficiency of learning and patient safety, research in simulation is essential. Two types of simulators currently in use include virtual reality and box trainers. Our study examined which simulator technique was most effective in teaching novice trainees laparoscopic techniques.nnnDESIGNnThis is a prospective, randomized, blinded, controlled trial that enrolled fourth-year medical students and surgical interns to participate in a supervised 6-month laparoscopic training program with either computer simulators or box trainers. Subjects were randomized and trained on appropriate laparoscopic camera skills, instrument handling, object positioning, dissection, ligation, suturing, and knot tying. Students within one group were not allowed to practice, learn or train on the opposing trainers. At time points 0, 2, and 6 months all subjects completed a series of laparoscopic exercises in a live porcine model, which were captured on DVD and scored by blinded expert investigators.nnnRESULTSnScores improved overall from the pretest to subsequent tests after training with no difference between the virtual reality and box simulator groups. In the medical students specifically, there was overall improvement, and improvement in the needle-transfer and knot-tying skills specifically, with no difference between the box simulator and virtual reality groups. For the interns, both groups showed significant overall improvement with no difference between the virtual reality and box simulator groups or on individual skills.nnnCONCLUSIONSnWe conclude that laparoscopic simulator training improves surgical skills in novice trainees. We found both the box trainers and the virtual reality simulators are equally effective means of teaching laparoscopic skills to novice learners.

Algorithm to diagnose etiology of hypoglycemia after Roux-en-Y gastric bypass for morbid obesity: case series and review of the literature

BACKGROUNDnGastric bypass is a proven treatment option for weight loss and the reduction of medical co-morbid conditions in the obese population. Severe refractory and/or recurrent hypoglycemia can occur, especially in postoperative patients who do not comply with the guidelines for oral glucose consumption. In a very small number of patients, the cause is not dietary indiscretions but, instead, factitious insulin administration or nesidioblastosis. The optimal evaluation and management for these diagnoses is not completely lucid yet important for bariatric surgeons and physicians alike to be familiar. Our objectives were to review the appropriate evaluation and treatment options for etiologies of hypoglycemia after gastric bypass and to create an algorithm that biochemically assesses the etiology of hypoglycemia. The setting was a university hospital in the United States.nnnMETHODSnWe present the cases of 3 patients who developed symptomatic hypoglycemia from distinct etiologies after laparoscopic Roux-en-Y gastric bypass. We also reviewed the current data regarding diagnosis and treatment.nnnRESULTSnEach patients evaluation and management is elaborated in detail. We propose a novel algorithm for the biochemical evaluation of hypoglycemia after gastric bypass according to our experience and the review of the literature.nnnCONCLUSIONnMost cases of symptomatic hypoglycemia that develop in gastric bypass patients are associated with dietary indiscretions. However, a small subset of patients can develop refractory, recurrent, hyperinsulinemic hypoglycemia from factitious insulin administration or nesidioblastosis.

Comparison of Outcomes and the Use of Multimodality Therapy in Young and Elderly People Undergoing Surgical Resection of Pancreatic Cancer

To compare outcomes and the use of multimodality therapy in young and elderly people with pancreatic cancer undergoing surgical resection.

Incidence of benign disease in patients that underwent resection for presumed pancreatic cancer diagnosed by endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA)

IntroductionThe lack of accurate markers makes preoperative differentiation between pancreatic cancer and non-malignant head lesions clinically challenging. In this study, we investigated the incidence of benign disease in patients that underwent resection for presumed pancreatic cancer diagnosed by EUS and EUS-guided FNA.MethodsMedical records of consecutive patients who underwent pancreaticoduodenectomy at Duke University were reviewed. Demographics, clinicopathologic characteristics, preoperative imaging, EUS, EUS-guided FNA, and postoperative outcomes were analyzed.ResultsSeven percent of the total 494 patients studied were found to have benign disease on postoperative pathology. Fifty-nine percent of these patients with benign disease underwent preoperative EUS. EUS was positive for a head mass in 70%, demonstrated enlarged lymph nodes in 27%, and showed signs concerning for vascular invasion in 13%. FNA was suspicious or indeterminate for cancer in 63% of patients. Postoperative complications occurred in 47% and one patient died after surgery. The overall pancreatic leak rate was 15%.ConclusionsEven with aggressive use of preoperative evaluation, there is still a small subset of patients where malignancy cannot be excluded without pancreaticoduodenectomy.

Vascular surgery collaboration during pancreaticoduodenectomy with vascular reconstruction.

BACKGROUNDnOnce thought to have unresectable disease, pancreatic cancer patients with portal venous involvement are now reported to have comparable survival after pancreaticoduodenectomy (PD) with vascular reconstruction (VR) as compared with patients without vascular involvement. We hypothesize that a multidisciplinary approach involving a vascular surgeon will minimize morbidity and improve patency of VRs.nnnMETHODSnWe identified 204 patients who underwent PD for pancreatic adenocarcinoma from 1997 to 2008. Patients who underwent PD with VR (N = 42) were compared with those who underwent standard PD (N = 162). VRs were performed by a vascular surgeon and involved primary repair (N = 8), vein patch (N = 25), or interposition grafting (N = 9) with femoral or other venous conduit.nnnRESULTSnPatients undergoing PD with VR had larger tumors (3.0 cm vs. 2.5 cm, P < 0.01) but did not have different rates of tumor-free margins (73% vs. 72%, P = 0.84) or lymph nodes metastases (50% vs. 38%, P = 0.14). The VR group had higher median blood loss (875 mL vs. 550 mL, P = 0<0.01), but no differences in mortality, complication rates, length of stay, or readmission rates were found in a median follow-up of 29 months. Overall survival rates were similar. Predictors of mortality on multivariate analysis included increasing histological grade (P = 0.01), positive lymph nodes (P = 0.01), and increasing tumor size (P = 0.01), but not VR (P = 0.28). When evaluated by computed tomography scans within 6 months postoperatively, 97% of reconstructions remained patent.nnnCONCLUSIONSnThe need for VR is not a contraindication to potentially curative resection in patients with pancreatic adenocarcinoma. Assistance of a vascular surgeon during VR may allow moderate-volume centers to achieve outcomes comparable with high-volume centers.

Defining Criteria for Selective Operative Management of Pancreatic Cystic Lesions: Does Size Really Matter?

IntroductionProposed criteria for resection of pancreatic cystic lesions have included symptoms, size (>3xa0cm), and suspicious features by endoscopic ultrasound (EUS). The objective of this study was to evaluate risk factors for malignancy in a large series of patients undergoing resection of suspected pancreatic cystic neoplasms.MethodsMedical records of patients selected for resection of pancreatic cystic lesions at Duke University Medical Center from 2000 to 2008 were reviewed. Lesions with solid components on cross-sectional imaging were excluded. Malignancy was defined as invasive or in situ carcinoma.ResultsAfter review, 101 patients were confirmed to have undergone resection for suspected cystic neoplasms of the pancreas. Preoperative EUS was performed in 71 patients. Sixteen patients (16%) had malignant lesions (preoperative size 1.5–5.9xa0cm). There was no clear association between size and malignancy. Male gender, biliary ductal dilatation (BDD), pancreatic ductal dilatation (PDD), and suspicious cytology (but not age, symptoms, or size) were associated with increased risk of malignancy. When factors available for all patients were incorporated into a multivariate model, only BDD and PDD were independent risk factors for malignancy. Only one patient with malignancy had neither BDD nor PDD but did have solid components by EUS.ConclusionsIn patients selected for resection, size was not an independent risk factor for malignancy. While size might be appropriate for stratification of asymptomatic patients with simple cysts, size should not be used as a selection criterion for patients who have cysts with solid components or with associated BDD or PDD.

Modified Puestow Lateral Pancreaticojejunostomy

IntroductionThere are various surgical options for the treatment of pain associated with chronic pancreatitis. The modified Puestow lateral pancreaticojejunostomy has been proven to be effective in ameliorating symptoms and expediting return to normal lifestyle while maintaining a low rate of morbidity and mortality. However, the debate regarding which surgical treatment provides the best outcomes is controversial.ObjectivesThe aims of this manuscript are to identify the patient population for which the Puestow benefits the most and discuss the pertinent technical aspects of the surgical procedure.

Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases

INTRODUCTIONnNomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC).nnnMETHODSnAn external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram.nnnRESULTSnAfter median follow-up of 30.4 months (range 0.33-150), Kaplan-Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram-predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n= 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P= 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients.nnnCONCLUSIONSnThe CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy.

Management of Bleeding from the Pancreas

Acute hemorrhage originating from the pancreas is the least common form of gastrointestinal bleeding. Patients typically present with a triad of epigastric abdominal pain, intermittent gastrointestinal hemorrhage, and hyperamylasemia. Diagnosis is challenging but can be made through a combination of upper endoscopy, endoscopic retrogradge cholangiopancreatography, endoscopic ultrasound, computed tomography angiography, and angiography. First line treatment in stable patients is endovascular. In unstable patients, operative intervention is required.