Louis H. Stein

Intraductal Papillary Mucinous Neoplasm (IPMN) with Extra-Pancreatic Mucin: A Case Series and Review of the Literature

BackgroundIntraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized pancreatic neoplasm characterized by excessive mucin secretion by ductal epithelial cells resulting in a cystic dilation of the pancreatic duct.AimThe objective of this study was to review Thomas Jefferson University’s experience and the literature to determine the significance of extra-pancreatic mucin when associated with an IPMN.ResultsA retrospective analysis at our institution revealed only two cases of IPMN associated with extra-pancreatic mucin, which were classic IPMNs with rupture of the pancreatic duct and peritoneal mucin spillage. This specific finding is not previously described, although is assumed as five cases were reported in the literature with IPMN and mucin extension demonstrated by pseudomyxoma peritonei (PMP). We propose IPMN of the pancreas may be grossly compared to a mucocele of the appendix, as both are characterized by excessive secretion of mucin by ductal epithelial cells. A morbid complication of a mucocele is PMP. The presence of extra-pancreatic mucin with an IPMN could present a rare but important marker of the eventual seeding of tumor outside the primary IPMN. This has been documented with cases of iatrogenic spilling of pancreatic mucin, as well as multiple cases of IPMN associated with pseudomyxoma peritonei.ConclusionsAt this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin.

Eosinophils Utilize Multiple Chemokine Receptors for Chemotaxis to the Parasitic Nematode Strongyloides stercoralis

Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S. stercoralis would trigger eosinophil chemotaxis, and to then compare the chemotactic migration response, including second messenger signals and receptors, to those mechanisms triggered by host chemoattractants. Eosinophils undergo both chemotaxis and chemokinesis to soluble parasite extract in transwell plates. Pretreatment of eosinophils with pertussis toxin, a G protein-coupled receptor inhibitor, inhibited migration of the eosinophils to the parasite extract. Likewise, blocking PI3K, tyrosine kinase, p38 and p44/42 inhibited eosinophil chemotaxis to parasite extract. Furthermore, CCR3, CXCR4 or CXCR2 antagonists significantly inhibited eosinophil chemotaxis to the parasite extract. Molecular weight fractionation of parasite extract revealed that molecules attracting eosinophils were present in several fractions, with molecules greater than 30 kDa being the most potent. Treating the extract with proteinase K or chitinase significantly inhibited its ability to induce chemotaxis, thereby demonstrating that the chemoattractants were both protein and chitin. Therefore, chemoattractants derived from parasites and host species stimulate similar receptors and second messenger signals to induce eosinophil chemotaxis. Parasite extract stimulates multiple receptors on the eosinophil surface, which ensures a robust innate immune response to the parasite.

Signaling through Gαi2 protein is required for recruitment of neutrophils for antibody‐mediated elimination of larval Strongyloides stercoralis in mice

The heterotrimeric guanine nucleotide‐binding protein Gαi2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Gαi2−/− mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN‐γ and IL‐4. The goal of the present study was to determine if a deficiency in the Gαi2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL‐4‐, IL‐5‐, and IgM‐dependent. Gαi2−/− and wild‐type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. Gαi2−/− mice failed to kill the larvae in the challenge infection as compared with wild‐type mice despite developing an antigen‐specific Th2 response characterized by increased IL‐4, IL‐5, IgM, and IgG. Transfer of serum collected from immunized Gαi2−/− mice to naïve wild‐type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in Gαi2−/− mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized Gαi2−/− mice. However, cell transfer studies demonstrated that neutrophils from Gαi2−/− mice are competent in killing larvae. These data demonstrate that Gαi2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, Gαi2 is essential for the recruitment of neutrophils required for host‐dependent killing of larvae.

The Novel Triad of Dorsal Agenesis of the Pancreas with Concurrent Pancreatic Ductal Adenocarcinoma and Nonalcoholic Chronic Calcific Pancreatitis: A Case Series and Review of the Literature

IntroductionDorsal agenesis of the pancreas (DAP) is a rare congenital anomaly, with only 44 cases having been reported in the English literature since 1966.Materials and MethodsA retrospective review of our IRB-approved pancreatic surgery database was performed from November 2005 to November 2010 searching for cases of DAP.DiscussionDisorders in the retinoic acid (Raldh) and hedgehog (Hh) signaling pathways, which appear to play a role in the development of DAP, have been implicated in other diseases of the pancreas such as pancreatic ductal adenocarcinoma (PDA) and nonalcoholic chronic calcific pancreatitis (NCCP).ConclusionIn this report, we describe three cases of DAP in the setting of PDA, two of which include the third component of NCCP. We provide a discussion of the clinical features of this novel triad and address the molecular pathways that relate to these respective diseases.

Epidemiology and Natural History of Thoraco-Abdominal Aortic Aneurysms

In spite of their rarity, thoraco-abdominal aortic aneurysms (TAAAs) present unique challenges. From a cellular perspective, TAAAs are associated with apoptosis of smooth muscle cells along with derangements in the molecular structure of elastin, collagen, and fibrillin. The risk of rupture increases with aortic diameter, with a dramatic increase at diameters >7.2 cm. Data from tertiary centers suggest TAAAs comprise 6% of all thoracic aortic aneurysms (TAAs). Genetics play an important role in aortic aneurysms. Ascending aortic aneurysms (AAAs) cluster in families, but TAAAs occur in families with a history of AAA. Chronic obstructive pulmonary disease and hypertension are associated with an increased risk of TAAAs rupture. Smoking is linked to the rate of aneurysm growth. We have just begun to understand the behavior of TAAA. Continued study will permit better identification of patients at risk of TAAA and the optimal timing of intervention.

Bleeding Diatheses and Preoperative Screening

Bleeding disorders pose a significant perioperative risk. Surgeons and surgical consultants should have a working knowledge of the cell-based coagulation model. Careful screening for bleeding diatheses begins with a careful history and physical examination. It is paramount to ascertain what medications and nonprescribed supplements and herbal preparations a patient is taking, as these medications can have significant effects on perioperative bleeding tendencies. Finally, screening laboratory-based coagulation assays are available. These must be used judiciously with regard to a patients history and the clinical circumstances surrounding the surgical stressor.

Can the occurrence of gastrointestinal bleeding in nonpulsatile left ventricular assist device patients provide clues for the reversal of arteriosclerosis

This article is written not only to explore the deleterious effects of nonpulsatile flow (namely, gastrointestinal [GI] bleeding), but also to propose the novel concept that deliberate induction of nonpulsatile flow might be harnessed to produce beneficial remodeling in arteriosclerotic arteries. Continuous-flow left ventricular assist devices have proven their efficacy in the treatment of end-stage heart disease. They are a reliable option in bridge-to-transplant and destination therapy. An enigmatic consequence of this therapy has been occult GI bleeding.

The Use of Intraoperative Doppler Assessment to Guide the Surgical Treatment of Anomalous Right Coronary Arteries

Abstract  Despite its rarity, anomalous origin of the right coronary artery (RCA) from the left coronary sinus can pose risk of sudden death. Because of this risk, many patients elect surgical correction of this anomaly. Surgical strategies for correction of this include ostioplasty, coronary artery reimplantation, and, more commonly, coronary artery bypass grafting. After coronary artery bypass grafting, some advocate ligation of the proximal RCA, speculating that competitive flow will cause graft failure. As no objective criteria for this have been established, we propose a method using of intraoperative Doppler flow measurements to guide the decision to preserve the proximal anomalous native vessel. We present three cases in which an RCA with an anomalous origin from the left sinus was corrected with coronary artery bypass grafting with the assistance of intraoperative Doppler flow measurements to guide the decision to preserve the proximal anomalous native vessel. In each case, the RCA was bypassed using a saphenous vein graft (SVG) that was used to bypass origin of the RCA. Flow through the graft was compared with and without ligation of the proximal RCA, before creation of the proximal anastomosis. In each case, flow through the SVG was not significantly reduced with the proximal RCA patent and ligation was not performed.