Management of Intraductal Papillary Mucinous Neoplasms: Controversies in Guidelines and Future Perspectives

Purpose of review

Management of intraductal papillary mucinous neoplasm (IPMN) is currently based on consensus, in the absence of evidence-based guidelines. In recent years, several consensus guidelines have been published, with distinct management strategies. In this review, we will discuss these discrepancies, in order to guide treating physicians in clinical management.

Recent findings

The detection rate of pancreatic cysts has increased substantially with the expanded use of high-quality imaging techniques to up to 45%. Of these cysts, 24–82% are IPMNs, which harbour a malignant potential. Timely detection of high-risk lesions is therefore of great importance. Surgical management is based on the presence of clinical and morphological high-risk features, yet the majority of resected specimens appear to be low risk.

Summary

International collaboration and incentive large-scale prospective registries of individuals undergoing cyst surveillance are needed to accumulate unbiased data and develop evidence-based guidelines. Additionally, development of non-invasive, accurate diagnostic tools (e.g. biomarkers) is needed to differentiate between neoplastic and non-neoplastic pancreatic cysts and detect malignant transformation at an early stage (i.e. high-grade dysplasia).

     

Xbves is a regulator of epithelial movement during early Xenopus laevis development

Bves/pop1a is a unique, highly conserved integral membrane protein expressed in embryonic epithelia and striated muscle. Although studies have proposed a role in epithelial morphogenesis, the function of Bves/pop1a in development is completely unknown. Here we show that Xenopus laevis Bves (Xbves) RNA and protein are expressed in epithelia of the early embryo. Transfection of Xbves into nonadherent mouse L cells confers cell/cell adhesion. Global inhibition of Xbves function by morpholino injection into two-cell embryos arrests development at gastrulation by deregulating the epithelial movements of epiboly and involution. Clonal inhibition of Xbves activity within the A1 blastomere and its derivatives completely randomizes movement of its progeny within otherwise normally differentiating embryos. These data demonstrate that Bves/pop1a proteins play a critical role in epithelial morphogenesis and, specifically, in the cell movements essential for epithelial rearrangements that occur during X. laevis development.     

Personality traits and psychological reactions to mental stress of female migraine patients

The purpose of this study was (i) to compare a range of stress-related personality traits, including defense and coping mechanisms, of migraine patients (n = 23) with those of tension headache patients (n = 18) and dermatologically afflicted, but otherwise healthy, controls (n = 22), and (ii) to compare their state anxiety and other moods before, during, and after the presentation of a psychological stressor (mental arithmetic). For all three groups, mental arithmetic induced a significant increase in state anxiety and mood disturbance, followed by a subsequent decrease during recovery. Migraine patients were not found to have a higher disposition for anxiety, depression, or rigidity than tension headache patients or controls. Between the headache groups no differences in the use of defense and coping mechanisms were found. Compared to the control group, however, both migraine patients and tension headache patients were more inclined to use internally focused defense mechanisms and less inclined to seek social support when confronted with a problem. The psychological reaction of migraine patients to mental stress hardly differed from tension headache and control subjects. Compared to the control subjects, however, both groups of headache patients exhibited a diminished recovery from feelings of vigour, depression, and fatigue due to the stress induced. It is suggested that this distinct psychological reaction to stress of headache patients versus healthy control subjects is related to the more internally focused defense style of the headache sufferers. Thus, in contrast to previous results, this study does not present evidence of a migraine personality. It suggests the development of specific personality characteristics as a consequence of suffering from episodic headache.     

Reciprocal ST segment depression: impact on the electrocardiographic diagnosis of ST segment elevation acute myocardial infarction.

Acute myocardial infarction (AMI) is one of many causes of electrocardiographic ST segment elevation (STE) in ED chest pain (CP) patients; at times, the electrocardiographic diagnosis may be difficult. Coexistent ST segment depression has been reported to assist in the differentiation of non-infarction causes of STE from AMI-related ST segment elevation. The objective was to determine the effect of AMI diagnosis on the presence of STD among ED CP patients with electrocardiographic STE. Adult CP patients with electrocardiographic STE in at least 2 anatomically distributed leads were reviewed for the presence or absence of ST segment depression in at least 1 lead and separated into 2 groups, both with and without ST segment depression. A comparison of the 2 groups was performed in 2 approaches: all STE patients and then only with STE patients who lacked confounding electrocardiographic pattern (bundle branch block [BBB], left ventricular hypertrophy [LVH], or right ventricular paced rhythm [VPR]). All patients in the study underwent prolonged observation in the ED (at least 8 hours) with 3 serial troponin T determinations and 3 electrocardiograms (ECG). AMI was diagnosed by abnormal serum troponin T values (>0.1 mg/dL); electrocardiographic STE diagnoses of non-AMI causes were determined by medical record review. There were 171 CP patients with STE were entered in the study with 112 (65.5%) individuals show ST segment depression. When considering all study patients, ST segment depression was present at statistically equal rates in AMI and non-AMI situations (P = NS). The sensitivity, specificity, positive predictive value, and negative predictive value for the electrocardiographic diagnosis of AMI were 63%, 34%, 30%, and 67%, respectively. Patients with confounding patterns (LVH 46, BBB 19, and VPR 6) were removed from the analysis group, leaving 100 patients for analysis; 38 of these patients had ST segment depression. When considering this group of study patients, ST segment depression was present significantly more often in AMI patients (P <.0001). The sensitivity, specificity, positive predictive value, and negative predictive value for the electrocardiographic diagnosis of AMI were 69%, 93%, 93%, and 71%, respectively. Clinical diagnoses were as follows: 56 AMI, 50 USAP, and 65 noncoronary syndrome. When all CP patients with electrocardiographic STE are considered, the presence of ST segment depression is not helpful in distinguishing AMI from non-AMI. If one considers only patterns which lack electrocardiographic ST segment depression caused by altered intraventricular conduction, the presence of ST segment depression strongly suggests the diagnosis of AMI. In these cases, reciprocal ST segment depression is of considerable value in establishing the electrocardiographic diagnosis of STE AMI.     

Characterization of the chemotactic defect in polymorphonuclear leukocytes exposed to influenza virus in vitro

The mechanism by which influenza virus interferes with polymorphonuclear leukocyte (PMN) chemotaxis was investigated. Incubation of human PMN with influenza A virus in vitro for 30 minutes significantly decreased PMN migration under agarose in response to N- formyl-methionyl-leucyl-phenylalanine (FMLP) or zymosan-activated serum. Virus-treated PMN tended to aggregate in the under-agarose assay. Aggregation was avoided by using a more dilute PMN suspension in filter assays. Virus treatment significantly decreased migration through 100-micron thick cellulose nitrate filters but had no effect on migration through 10-micron thick polycarbonate filters or on PMN bipolar shape change. Virus was not chemotactic in the polycarbonate filter assay and did not induce shape change in purified PMN. It was concluded that influenza virus did not interfere with the ability of PMN to recognize a chemoattractant, undergo shape change, and move a short distance but did limit the extent of migration. Inhibition could not be explained by chemotactic deactivation, since the virus was not chemotactic.     

Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.     

A distinct profile of six soluble adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin, L-selectin and P-selectin) in rheumatoid arthritis

Soluble forms of ICAM-1, VCAM-1, E-selectin, L-selectin, P-selectin and, more recently, ICAM-3 are known to exist in human serum and have elevated levels in numerous diseases. Previous studies have demonstrated that in rheumatoid arthritis (RA) the levels of circulating sICAM-1 and sE-selectin are elevated relative to healthy controls. We have compared the serum profiles of these six soluble adhesion molecules in patients with RA (n = 22) to those seen in healthy controls (n = 10) using sandwich ELISA. In the patients, there were significant elevations of serum sICAM-1 (P < 0.0001), sICAM-3 (P = 0.0327), sVCAM-1 (P = 0.0025), sL-selectin (P = 0.0194) and sP-selectin (P = 0.0025), but not E-selectin (P = 0.0672). However, only sP- selectin was found to correlate with disease activity in the patients (r = 0.461, P < 0.05). Thus, there is a distinct profile of soluble adhesion molecules in RA of which only sP-selectin correlates with disease activity.