Management of Solid-pseudopapillary Neoplasms of the Pancreas: a Comparison with Standard Pancreatic Neoplasms

BACKGROUND: Solid-pseudopapillary neoplasms (SPNs) of the pancreas are increasingly diagnosed, but the exact surgical management in terms of extent of the resection is not well defined. MATERIALS AND METHODS: Patients operated on in our hospital between January 1993 and March 2005 formed the study groups. RESULTS: From 659 consecutive resections for pancreatic neoplasms, 12 female patients (1.8%) with a median age of 21 years who underwent resection for (SPN) are compared with the remaining 647 pancreatic resection patients. Jaundice (SPN 0 versus PR 73%, p < 0.001) and weight loss (SPN 0 versus PR 49%, p = 0.001) occurred significantly less often. Neoplasms were distributed equally among the pancreatic head (SPN 5 out of 12 patients versus PR 88%, p < 0.001) and corpus/tail (SPN 6 out of 12 patients versus PR 8%, p < 0.001). The operative time was significantly shorter (SPN 233 min versus PR 280 min, p = 0.012), and there were significantly fewer complications (SPN 1 of 12 patients versus PR 48%, p = 0.007). The mortality was not different (SPN 0 versus PR 1.6%, p = 1.000), and the hospital stay was significantly shorter (SPN 9 days versus PR 15 days, p = 0.012). The median size of the neoplasms was significantly larger (SPN 6.9 cm versus PR 2.5 cm). The median number of lymph nodes harvested was significantly fewer (SPN 1 versus PR 6, p = 0.001), and lymph node metastases occurred significantly less often (SPN 0 versus PR 64%, p < 0.001). The 5-year survival of SPN patients was 100% and is significantly better compared with survival of patients with pancreatic adenocarcinoma (12%, p < 0.001) and ampulla of Vater adenocarcinoma (22%, p = 0.005). CONCLUSIONS: Patients with solid-pseudopapillary neoplasms of the pancreas present differently and the course of the disease is more benign. These patients can be adequately managed by pylorus-preserving pancreatoduodenectomy or spleen-preserving distal pancreatectomy with excellent early and long-term result

Neurodegenerative Properties of Chronic Pain: Cognitive Decline in Patients with Chronic Pancreatitis

Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients

The Impact of Forced Answering and Reactance on Answering Behavior in Online Surveys

Forced answering (FA) is a frequent answer format in online surveys that forces respondents to answer each question in order to proceed through the questionnaire. The underlying rationale is to decrease the amount of missing data. Despite its popularity, empirical research on the impact of FA on respondents’ answering behavior is scarce and has generated mixed findings. In fact, some quasi-experimental studies showed that FA has detrimental consequences such as increased survey dropout rates and faking behavior. Notably, a theoretical psychological process driving these effects has hitherto not been identified. Therefore, the aim of the present study was twofold: First, we sought to experimentally replicate detrimental effects of FA on online questionnaire data quality. Second, we tried to uncover an explanatory psychological mechanism. Specifically, we hypothesized that FA effects are mediated through reactance. Zero-order effects showed that FA increased state reactance and questionnaire dropout as well as reduced answer length in open-ended questions. Results of survival and mediation analyses corroborate negative FA effects on data quality and the proposed psychological process

Multiple cross-reactive self-ligands for Borrelia burgdorferi-specific HLA-DR4-restricted T cells.

T cell recognition of self antigens is a key event in the pathogenesis of autoimmune diseases. To date, the initial events that trigger autoreactive T cells are unknown. The "molecular mimicry" hypothesis predicts that during an infection T cells that recognize both a microbial antigen and a related self peptide become activated and cause autoimmune disease. We have systematically examined the recognition of self antigens by HLA-DR4-restricted T cells specific for peptides of the outer surface protein A (OspA) of Borrelia burgdorferi, the etiological agent of Lyme disease. We used the peptide spot synthesis technique for complete peptide substitution analyses of two immunodominant OspA epitopes. Each amino acid residue of the epitopes was substituted with all 20 naturally occurring amino acids and the altered peptides were tested for recognition by a panel of OspA-specific T cells. The binding motifs (supertopes) revealed by these analyses were used to screen public databases for matching human or murine peptides. Several hundred peptides were identified by this search and synthesized. Of these, 28 were recognized by OspA-specific T cells. Thus, T cell cross-reactivity is a common phenomenon and the existence of cross-reactive epitopes alone does not imply molecular mimicry-mediated pathology and autoimmunity

Cross-reactive binding of cyclic peptides to an anti-TGFalpha antibody fab fragment: an X-ray structural and thermodynamic analysis

The monoclonal antibody tAb2 binds the N-terminal sequence of transforming growth factor α, VVSHFND. With the help of combinatorial peptide libraries it is possible to find homologous peptides that bind tAb2 with an affinity similar to that of the epitope. The conformational flexibility of short peptides can be constrained by cyclization in order to improve their affinity to the antibody and their stability towards proteolysis. Two cyclic peptides which are cross-reactive binders for tAb2 were selected earlier using combinatorial peptide libraries. One is cyclized by an amide bond between the N-alpha group and the side-chain of the last residue (cyclo-SHFNEYE), and the other by a disulfide bridge (cyclo-CSHFNDYC). The complex structures of tAb2 with the linear epitope peptide VVSHFND and with cyclo-SHFNEYE were determined by X-ray diffraction. Both peptides show a similar conformation and binding pattern in the complex. The linear peptide SHFNEYE does not bind tAb2, but cyclo-SHFNEYE is stabilized in a loop conformation suitable for binding. Hence the cyclization counteracts the exchange of aspartate in the epitope sequence to glutamate. Isothermal titration calorimetry was used to characterize the binding energetics of tAb2 with the two cyclic peptides and the epitope peptide. The binding reactions are enthalpically driven with an unfavorable entropic contribution under all measured conditions. The association reactions are characterized by negative ΔC p changes and by the uptake of one proton per binding site. A putative candidate for proton uptake during binding is the histidine residue in each of the peptides. Hydrogen bonds and the putative formation of an electrostatic pair between the protonated histidine and a carboxy group may contribute markedly to the favorable enthalpy of complex formation. Implications to cyclization of peptides for stabilization are discussed