Colchicine in Cardiovascular Disease: In-Depth Review.

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.

Early arrhythmia recurrence after cryoballoon ablation in atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Early arrhythmia recurrence within the 3-month blanking period is a common event that historically has been attributed to reversible phenomena. While its mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation. METHODS: The MEDLINE database, ClinicalTrials. gov, medRxiv, and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for atrial fibrillation. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence. RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (odds ratio [OR]: 5.31; 95% confidence interval [CI]: 3.75-7.51). This pattern remained unchanged after subanalyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting antiarrhythmic drug utilization during the blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity. CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier reintervention is an open research avenue.

Right ventricular outflow tract low-voltage areas identify the site of origin of idiopathic ventricular arrhythmias: A high-density mapping study.

INTRODUCTION: Electronatomical mapping allows direct and accurate visualization of myocardial abnormalities. This study investigated whether high-density endocardial bipolar voltage mapping of the right ventricular outflow tract (RVOT) during sinus rhythm may guide catheter ablation of idiopathic ventricular arrhythmias (VAs). METHODS AND RESULTS: Forty-four patients (18 males, mean age: 38.1 ± 13.8 years) with idiopathic RVOT VAs and negative cardiac magnetic resonance imaging underwent a stepwise mapping approach for the identification of the site of origin (SOO). High-density electronatomical mapping (1096.6 ± 322.3 points) was performed during sinus rhythm and identified at least two low bipolar voltage areas less than 1 mV (mean amplitude of 0.20 ± 0.10 mV) in 39 of 44 patients. The mean low-voltage surface area was 1.4 ± 0.8 cm2 . Group 1 consisted of 28 patients exhibiting low-voltage areas and high-arrhythmia burden during the procedure. Pace match to the clinical VAs was produced in one of these low-voltage areas. Activation mapping established the SOO at these sites in 27 of 28 cases. Group 2 comprised 11 patients exhibiting abnormal electroanatomical mapping, but very low-arrhythmia burden during the procedure. Pace mapping produced a near-perfect or perfect match to the clinical VAs in one of these areas in 9 of 11 patients which was marked as potential SOO and targeted for ablation. During the follow-up period, 25 of 28 patients from group 1 (89%) and 7 of 9 patients from group 2 (78%) were free from VAs. CONCLUSIONS: Small but detectable very low-voltage areas during mapping in sinus rhythm characterize the arrhythmogenic substrate of idiopathic RVOT VAs and may guide successful catheter ablation.

Dyspnea in patients treated with P2Y12 receptor antagonists: insights from the GReek AntiPlatElet (GRAPE) registry.

In 'real life' acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87-3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y12 receptor antagonist, dyspnea occurs commonly, particularly when ticagrelor is administered. Non-persistence with antiplatelet agents at discharge is more frequently observed among dyspnea-reporters.

Adenosine-Guided Pulmonary Vein Antral Isolation for Paroxysmal Atrial Fibrillation: A Randomized Study.

OBJECTIVES: The prognostic significance of adenosine-mediated pulmonary vein (PV) dormant conduction and whether such conduction should be eliminated still remain controversial. This randomized study aimed to investigate whether adenosine-guided ablation of the reconnection gaps improves the long-term outcomes of pulmonary vein antral isolation (PVAI) for paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients with paroxysmal AF were randomly assigned to undergo (n = 80, group 1) or not (n = 81, group 2) adenosine testing following PVAI. Adenosine-mediated PV dormant conduction was unmasked in 26 patients (32.5%) of group 1. Successful elimination of the reconnection gaps was subsequently performed in all patients. During a mean follow-up period of 11.39 ± 5.10 months, 30 patients of group 1 (37.5%), and 27 patients of group 2 (33.3%) experienced arrhythmia recurrence. The Kaplan-Meier arrhythmia free survival curves failed to demonstrate any significant differences between study groups (log rank 0.217, P = 0.642). Fourteen of 26 (53.8%) patients with adenosine-mediated dormant conduction and subsequent elimination of reconnection gaps experienced AF recurrence during follow-up. On the contrary, only 16 of 54 patients without dormant conduction (29.6%) displayed arrhythmia recurrence (P = 0.049). Logistic regression analysis showed that adenosine-mediated PV reconnection (hazard ratio 0.292, 95% confidence interval 0.122-0.483; P = 0.01) was an independent predictor of AF recurrence. CONCLUSION: In this patients' cohort, adenosine-mediated PV reconnection is predictive of future arrhythmic events. Elimination of dormant conduction with additional ablation lesions does not improve the long-term outcome of the procedure compared to the standard PVAI.

The prognostic impact of diastolic dysfunction after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Diastolic dysfunction (DD) is a long-established marker of disease progression in patients with aortic valve stenosis (AS), indicating valvular myocardial damage. Recently, substantial observational data have emerged demonstrating that worse pre-operative DD assessed using echocardiography is associated with adverse long-term clinical outcomes after transcatheter aortic valve replacement (TAVR). AIM: To systematically appraise and quantitatively synthesize current evidence on the prognostic impact of echocardiographic severe DD derived by echocardiography before TAVR. METHODS: A systemic literature review was undertaken in electronic databases to identify studies reporting the predictive value of severe DD in AS subjects undergoing TAVR. A random-effects meta-analysis was conducted to quantify the adjusted and unadjusted hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACEs) for the presence of severe DD. RESULTS: Ten studies were deemed eligible for inclusion. Of those, 9 provided appropriate quantitative data for the meta-analysis, encompassing a total of 4,619 patients. The presence of severe DD was associated with increased risk for all-cause mortality (pooled unadjusted HR=2.56 [1.46-4.48]; p<0.01; I2=76 %) and MACEs (pooled unadjusted HR=1.82 [1.29-2.58]; p<0.01; I2=86 %). When adjusted for clinically-relevant parameters, the presence of severe DD retained independent association with all-cause mortality (pooled adjusted HR=2.35 [1.26-4.37]; p<0.01; I2=79 %) and MACEs (pooled adjusted HR= 2.52 [1.72-3.65]; p<0.01; I2=0 %). In subgroup analysis there was no difference on post-TAVR risk between the use of different diastolic function grading scores. CONCLUSION: Presence of severe DD assessed by echocardiography pre-TAVR is a major determinant of long-term adverse outcomes after the procedure.

Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review.

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?

Prognostic value of stress hyperglycemia ratio in patients with acute myocardial infarction: A systematic review with Bayesian and frequentist meta-analysis.

The present systematic review and meta-analysis aimed to investigate the prognostic value of stress hyperglycemia ratio (SHR) in patients with acute myocardial infarction (AMI). A total of 26 cohort studies, involving 87,974 patients, were analyzed. The frequentist meta-analysis showed that AMI patients with SHR in the upper quantile had a significantly higher hazard of major adverse cardiovascular and cerebrovascular events (MACCE, HR = 1.7; 95 % CI= [1.42, 2.03]; P < 0.001; I2 = 71 %; P <0.01), long-term (HR = 1.64; 95 % CI= [1.49, 1.8]; P < 0.001; I2 = 16 %; P = 0.29) and in-hospital all-cause mortality (OR = 3.87; 95 % CI= [2.98, 5.03]; P < 0.001; I2 = 54 %; P = 0.03) compared to those with lower SHR. Prespecified subgroup analyses revealed that these results were consistent irrespective of diabetes status (P = 0.32 and 0.73 for subgroup differences) and that SHR was a significant predictor of MACCE both in AMI with obstructive coronary arteries (HR = 1.57; 95 % CI= [1.34, 1.83]; P < 0.001; I2 = 66 %; P < 0.01) and MINOCA (HR = 2.57; 95 % CI= [1.86, 3.56]; P < 0.001; I2 = 0 %; P = 0.84). The Bayesian analyses with weakly prior assumptions yielded comparable results with the frequentist approach and provided strong evidence that higher SHR values were associated with significantly greater hazard of MACCE, short-term and long-term mortality. Further, prospective research is warranted to provide deeper insights into this newer index of stress hyperglycemia before its potential incorporation in clinical prediction scores.

Hands Deformity in a Patient with IgA Vasculitis.

74-year-old female patient with IgA vasculitis was referred for rheumatic evaluation due to arthritic complaints and hand deformities. Physical examination revealed reversible Jaccoud's arthropathy in both hands, with swan-neck type deformities, while no erosions were present in the X-Ray. Jaccoud's arthropathy is mainly observed can be present in patients with in Rheumatic Fever, Systemic Lupus Erythematosus, and Sjogren's syndrome. The absence of erosions distinguishes this entity from rheumatoid arthritis. There is no specific treatment other than the treatment of the underlying disease.

Inflammatory Biomarkers in Coronary Artery Ectasia: A Systematic Review and Meta-Analysis.

Isolated coronary artery ectasia (CAE) is a relatively rare clinical entity, the pathogenesis of which is poorly understood. More and more evidence is accumulating to suggest a critical inflammatory component. We aimed to elucidate any association between neutrophil to lymphocyte ratio and coronary artery ectasia. A systematic MEDLINE database, ClinicalTrials.gov, medRxiv, Scopus and Cochrane Library search was conducted: 50 studies were deemed relevant, reporting on difference in NLR levels between CAE patients and controls (primary endpoint) and/or on high-sensitive CRP, IL-6, TNF-a and RDW levels (secondary endpoint), and were included in our final analysis. (PROSPERO registration number: CRD42021224195). All inflammatory biomarkers under investigation were found higher in coronary artery ectasia patients as compared to healthy controls (NLR; SMD = 0.73; 95% CI: 0.27-1.20, hs-CRP; SMD = 0.96; 95% CI: 0.64-1.28, IL-6; SMD = 2.68; 95% CI: 0.95-4.41, TNF-a; SMD = 0.50; 95% CI: 0.24-0.75, RDW; SMD = 0.56; 95% CI: 0.26-0.87). The main limitations inherent in this analysis are small case-control studies of moderate quality and high statistical heterogeneity. Our findings underscore that inflammatory dysregulation is implicated in coronary artery ectasia and merits further investigation.

Repurposing colchicine's journey in view of drug-to-drug interactions. A review.

Colchicine's medical evolution is historically bound to the Mediterranean basin, since remarkable researchers from this region underscored its valuable properties. With the passing of years colchicine became an essential pharmaceutical substance for the treatment of rheumatologic and cardiovascular diseases. In light of recent findings, the therapeutic value of colchicine has grown. In clinical practice, colchicine remains underutilized in view of its proven efficacy and safety. Its complex pharmacokinetics and multifaceted anti-inflammatory role remain under investigation. The current review addresses the safe administration of colchicine in view of key drug to drug interactions. Finally, we are briefly presenting colchicine's future potential applications.

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine.

In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine's immunomodulating capacity in view of hindering coronavirus complications.

Staple line reinforcement in laparoscopic bariatric surgery: does it actually make a difference? A systematic review and meta-analysis.

BACKGROUND: Staple line leaks represent a major concern in all laparoscopic operations but are particularly important in bariatric surgery, where leak complications carry significant morbidity and mortality. Therefore, several means of staple line reinforcement have been described, but none is totally accepted. In this study, we attempt to illuminate any clear benefit of staple line reinforcement through a systematic review and meta-analysis of reported articles. METHODS: Two major databases (PubMed and Cochrane) were searched and assessed by two reviewers. Inclusion criteria were: detailed description of operative technique, especially concerning staple line reinforcement, and possible existence of proven staple line leak. Selected studies were evaluated by systematic review and meta-analysis according to their eligibility. The study population was finally divided into two groups: reinforcement (of any type) and no reinforcement. RESULTS: In the initial search, 126 studies were obtained. Then, 17 full papers, both randomised controlled trials (RCTs) and non-RCTs, were included in the systematic review. Seven studies, comprising 3,299 patients, were examined for evaluation of population odds of leak (7.69), which was considered clinically significant. Meta-analysis of three studies comprising 1,899 patients revealed no clear benefit of reinforcement group, though with marginal significance. CONCLUSIONS: Although several drawbacks exist, this study illustrates two important aspects: that current staplers may not be uniformly reliable, and that staple line reinforcement does not seem to have any clear benefit, at least concerning leak rate.

Accurate microRNA target prediction correlates with protein repression levels.

BACKGROUND: MicroRNAs are small endogenously expressed non-coding RNA molecules that regulate target gene expression through translation repression or messenger RNA degradation. MicroRNA regulation is performed through pairing of the microRNA to sites in the messenger RNA of protein coding genes. Since experimental identification of miRNA target genes poses difficulties, computational microRNA target prediction is one of the key means in deciphering the role of microRNAs in development and disease. RESULTS: DIANA-microT 3.0 is an algorithm for microRNA target prediction which is based on several parameters calculated individually for each microRNA and combines conserved and non-conserved microRNA recognition elements into a final prediction score, which correlates with protein production fold change. Specifically, for each predicted interaction the program reports a signal to noise ratio and a precision score which can be used as an indication of the false positive rate of the prediction. CONCLUSION: Recently, several computational target prediction programs were benchmarked based on a set of microRNA target genes identified by the pSILAC method. In this assessment DIANA-microT 3.0 was found to achieve the highest precision among the most widely used microRNA target prediction programs reaching approximately 66%. The DIANA-microT 3.0 prediction results are available online in a user friendly web server at http://www.microrna.gr/microT.

Successful pancreaticoduodenectomy with immediate vascular reconstruction in a patient with cancer of the pancreatic head and celiac artery stenosis. A case report.

CONTEXT: Celiac artery stenosis is observed in a significant percentage of individuals in the general population. Although usually clinically silent and insignificant, due to the presence of extensive collaterals between the celiac artery and the superior mesenteric artery, celiac artery stenosis may be associated with potentially catastrophic ischemic complications in patients undergoing pancreaticoduodenectomy, due to the abrupt interruption of the collateral pathways. Therefore, revascularization may be indicated in selected patients with celiac artery stenosis undergoing a PD. CASE REPORT: We present a patient with celiac artery stenosis diagnosed intraoperatively during a PD, who underwent vascular reconstruction at the time of the PD. In the immediate postoperative period, he developed hepatic ischemia due to stenosis at the anastomosis of the stent with the hepatic artery. He was subsequently treated successfully with the endovascular placement of a stent. In retrospect, a careful reevaluation of the preoperative abdominal CT scan showed the stenosis at the origin of celiac artery. CONCLUSION: A careful evaluation of abdominal CT scan is required to preoperatively identify this not uncommon vascular obstructive disease, especially in asymptomatic patients. Otherwise, the astute surgeon should suspect celiac artery stenosis based on intraoperative findings/changes immediately following ligation of the gastroduodenal artery during a PD.

Ischemic colitis: surging waves of update.

Ischemic colitis is the most common type of intestinal ischemia, and it represents the consequences of acute or, more commonly, chronic blockage of blood flow through arteries that supply the large intestine. Ischemic colitis is manifested through a continuum of injury and considered as an illness of the elderly. The incidence of ischemic colitis has been underestimated, because many mild cases may go unreported. Patients experience abdominal pain, usually, localized to the left side of the abdomen, along with tenderness and bloody diarrhea. Severe ischemia may lead to bowel necrosis and perforation, which results in an acute abdomen and shock, frequently, being accompanied by lactic acidosis. Although computed tomography may have indicative findings, colonoscopy is the golden standard of diagnosis. Supportive care with intravenous fluids, optimization of hemodynamic status, avoidance of vasoconstrictive drugs, bowel rest, and empiric antibiotics will produce clinical improvement within 1 to 2 days in most patients. The condition resolves completely with conservative treatment, in most cases, but late diagnosis or severe ischemia can be associated with high rates of complications and death. However, when the interruption to the blood supply is more severe or more prolonged, the affected portion of the large intestine may have to be surgically removed. The present paper aims at bringing ischemic colitis up to date, by reviewing the current medical literature and extracting the contemporary data, about its presentation, diagnosis and treatment, which is of benefit to the readership, who may encounter this potentially fatal entity.

Biomarkers Determining Prognosis of Atrial Fibrillation Ablation.

Catheter ablation for rhythm control is recommended in specific patient populations with paroxysmal, persistent, or long-standing persistent atrial fibrillation. Pulmonary vein isolation is the cornerstone of the ablative therapy for atrial fibrillation. However, relapse is still common since the single procedure efficacy of atrial fibrillation ablation was estimated to be 60-80% in paroxysmal and 50-70% in persistent atrial fibrillation. It is important to identify predictors of successful atrial fibrillation patients ablation. In the present review, we will assess the role of available biomarkers to predict responders of an initial atrial fibrillation catheter ablation. Emphasis has been given on the role of myocardial injury biomarkers, natriuretic peptides and traditional inflammatory markers. Novel inflammatory markers, oxidative stress biomarkers and microRNAs have also been examined as predictors of a successful atrial fibrillation procedure. Notably, the impact of procedural and short-term administration of steroids, as well as the role of colchicine on preventing atrial fibrillation recurrence after ablation is thoroughly presented.

Endpoints for Successful Slow Pathway Catheter Ablation in Typical and Atypical Atrioventricular Nodal Re-Entrant Tachycardia: A Contemporary, Multicenter Study.

OBJECTIVES: This study sought to investigate markers of success following slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT). BACKGROUND: Published data are conflicting. METHODS: The authors studied 1,007 patients with typical AVNRT and 77 patients with atypical AVNRT. RESULTS: Following ablation, tachycardia was rendered not inducible in all patients. One case of transient (0.09%) and 1 of permanent (0.09%) atrioventricular (AV) block were encountered. At a 3-month follow-up, arrhythmia recurrence was noted in 21 (2.10%) patients in the typical and 3 (3.90%) patients in the atypical group (odds ratio: 0.525; 95% confidence interval [CI]: 0.153 to 1.802; p = 0.298). To predict absence of recurrence in 3 months, the induction of junctional rhythm (95.70% in typical and 96.10% in atypical groups) had sensitivity of 95.9% (95% CI: 94.6% to 97.0%) and specificity of 4.20% (95% CI: 0.11% to 21.10%), while the absence of dual AV nodal conduction post-ablation had sensitivity of 65.2% (95% CI: 62.2% to 68.1%) and specificity of 33.30% (95% CI: 15.60% to 55.30%). Neither junctional rhythm nor residual dual AV nodal pathway conduction were predictive of arrhythmia recurrence by univariate analysis. In long-term follow-up data available for 239 patients, arrhythmia-free survival was not associated with the induction of junctional rhythm or the absence of residual dual AV nodal conduction (log-rank test, p = 0.819 and p = 0.226, respectively). CONCLUSIONS: Induction of a junctional rhythm during ablation is a sensitive but not a specific marker of success. Residual dual AV nodal conduction is not predictive of recurrence. Noninducibility of the arrhythmia, usually after ablation-induced junctional rhythm, and despite isoproterenol challenge, is the most credible endpoint for success.

The expression of matrix metalloproteinases-2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters.

AIM: To investigate the expression of metalloproteinase (MMP) -2, MMP-9 and tissue inhibitor of MMP (TIMP) -2 in pancreatic ductal and ampullary carcinoma and to test the findings for correlation with angiogenesis and several clinicopathological parameters. PATIENTS AND METHODS: Paraffin sections from 32 pancreatic ductal adenocarcinomas and 17 ampullary carcinomas were assessed for the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemistry. Stromal and epithelial staining was evaluated separately. Moreover, sections stained immunohistochemically with anti-CD34 antibody were evaluated by image analysis for the quantification of microvessel density (MVD). RESULTS: In pancreatic ductal adenocarcinoma, lower levels of glandular TIMP-2 were found in poorly differentiated tumors, while high glandular TIMP-2 expression was significantly associated with better survival. The age of the patients and the degree of differentiation of the tumor were identified as independent prognostic parameters. No relation was found between the expression of MMPs, TIMP or angiogenesis and the parameters under consideration. In ampullary adenocarcinoma, strong expression of glandular MMP-2 was associated with higher MVD values. Moreover, lymph vessel invasion was associated with higher stromal TIMP-2. CONCLUSION: In pancreatic ductal adenocarcinoma, TIMP-2 may have a more crucial role in prognosis than MMP-2, MMP-9 or angiogenesis. In ampullary adenocarcinoma, MMP-2 expression correlated with MVD, supporting its postulated role in angiogenesis.

Large somatostatin-producing endocrine carcinoma of the ampulla of vater in association with GIST in a patient with von Recklinghausen's disease. Case report and review of the literature.

CONTEXT: Somatostatin-producing endocrine tumors of the duodenum are very rare neoplasms of the gastrointestinal tract. These tumors may be associated with von Recklinghausen's disease. CASE REPORT: We present the case of a 49-year-old female patient with von Recklinghausen's disease and an incidentally diagnosed ampullary neoplasm. The patient was treated with a classical pancreaticoduodenectomy. At surgery, a mass was found in the greater curve of the stomach which was resected using the classic Whipple procedure. Histology and immunohistochemistry showed that the duodenal tumor was an ampullary somatostatin-producing endocrine carcinoma while the gastric tumor was a gastrointestinal stromal tumor (GIST). The postoperative course was uneventful and the patient is alive, without tumor recurrence, six years after surgery. CONCLUSION: Somatostatin-producing endocrine tumors of the duodenum are rare tumors, often associated with von Recklinghausen's disease; these neoplasms should be treated aggressively using radical surgical resection. Although local resection may be appropriate for small duodenal somatostatin-producing tumors, a pancreaticoduodenectomy is usually required for larger tumors.