Jacek Pajak

Histopathological diagnosis of microscopic colitis

A typical symptom of microscopic colitis (MC) is chronic watery diarrhea with normal endoscopic findings and characteristic inflammatory changes in histopathology. Treatment of the disease is mainly empiric. MC has two main subtypes: lymphocytic colitis and collagenous colitis. There are also untypical histopathological forms of MC: MC with giant cells, MC not otherwise specified (NOS) and cryptal lymphocytic coloproctitis. Some other histopathological changes in MC have been observed, especially Paneth cell hyperplasia or epithelial degeneration. Eosinophilic colitis, acute colitis, amyloidosis, ulcerative colitis and Crohn’s disease should be taken into consideration in differential diagnosis. The most reliable biopsy material for histopathological examination are samples obtained from transverse colon. Some studies proved that treatment of MC makes it possible to reduce not only clinical, but also histopathological, manifestations.

Colloid carcinoma of the pancreas: review of selected pathological and clinical aspects

&NA; Colloid carcinoma (CC) of the pancreas is a histopathological variant of ductal adenocarcinoma, which is characterised by the presence of large pools of extracellular mucin, containing neoplastic cells. The mucin component comprises at least 50% of CC (according to the definition by the World Health Organization) or at least 80% of the tumour (according to the US Armed Forces Institute of Pathology). In the vast majority of cases, CC develop from pre‐existing intraductal papillary mucinous neoplasms, especially those forming intestinal‐type papillae and characterised by MUC2 expression. Data concerning the long‐term prognosis in patients with CC are discrepant. In this review, the authors present contemporary definitions of CC, issues of its epidemiology, symptomatology, pre‐operative diagnostics, histopathology, treatment and prognosis. Special attention has been paid to pathogenesis of CC.

Experimental evaluation of pharmacokinetic profile and biological effect of a novel paclitaxel microcrystalline balloon coating in the iliofemoral territory of swine.

New paclitaxel coated balloons (PCB) developments have been proposed to maintain therapeutic levels of drug in the tissue while decreasing particle release. In this series of studies, we evaluated the pharmacokinetic profile and biological effects after paclitaxel delivery via novel microcrystalline PCB coating (mcPCB, Pax®, Balton) in porcine iliofemoral arteries. Methods: Ten domestic swine were enrolled yielding 24 iliofemoral segments for evaluation. In the pharmacokinetic study, nine mcPCBs were dilated for 60 sec and animals sacrificed after 1 hr, 3 and 7 days. Studied segments were harvested and tissue paclitaxel concentration was analyzed utilizing HPLC. In the biological response evaluation, self‐expandable stents were implanted followed by post dilation with either mcPCB (n = 10) or POBA (n = 5). After 28 days, angiography was performed, animals were sacrificed and stented segments harvested for histopathological evaluation. Results: The 1‐hr, 3 and 7 days vessel paclitaxel concentrations were 152.9 ± 154.5, 36.5 ± 49.5, and 0.9 ± 0.7 ng/mg respectively. In the biological response study, stents in the mcPCB group presented lower angiographic measures of neointimal hyperplasia as expressed by late loss when compared to POBA (−0.43 ± 0.9 vs. 0.23 ± 1.2; P = 0.24) at 28 days. In the histopathological evaluation, percent area of stenosis (%AS) was reduced by 42% in the mcPCB group (P < 0.05). The healing process in mcPCB group was comparable to POBA with regard to fibrin deposition (0.7 vs. 0.7; P = ns), neointimal maturity (1.97 vs. 1.93; P = ns), inflammation score (0.92 vs. 1; P = ns) and endothelialization score (1.77 vs. 1.73; P = ns). The mcPCB group did however display a greater tendency of medial cell loss and mineralization (60% vs. 0; P = 0.08). Conclusions: Delivery of paclitaxel via a novel mcPCB resulted in low long‐term tissue retention of paclitaxel. However, this technological approach displayed reduced neointimal proliferation and favorable healing profile.

Iron deficiency and hematological changes in adult patients after Fontan operation

BACKGROUND Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/μl vs. 4.8 ± 0.4 × 10(9)/μl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 μmol/l vs. 38.4 ± 11.9 μmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 μmol/l vs. 57.8 ± 8.5 μmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.

Aspirin resistance in adult patients after Fontan surgery

BACKGROUND Thrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease. OBJECTIVE To characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC). METHODS Thirty-four FC patients (age 18-40years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin-antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured. RESULTS Platelet numbers were significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin-antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6. CONCLUSION Adults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications.

Effects of local intracoronary paclitaxel delivery using the Remedy transport catheter on neointimal hyperplasia after stent implantation in a porcine model

PURPOSE To assess the effects of local paclitaxel delivery using the Remedy catheter on neointimal hyperplasia in a porcine model and compare these results to commercially available BMS and biodegradable polymer-coated paclitaxel-eluting stents (BP-PES). METHODS AND MATERIALS A total of 31 stents were implanted into coronary arteries of 15 domestic swine including eight BMS, six BP-PES, and 17 BMS after intravasal paclitaxel delivery at doses of 250 μg (LPD250; n=9) and 500 μg (LPD500, n=6). All stents were implanted under quantitative coronary angiography (QCA) guidance to achieve a balloon/artery diameter ratio of 1.15:1.0. Twenty-eight days after the procedure, follow-up coronary angiography was performed, the animals were euthanized, and the coronary arteries harvested for histopathological analysis. RESULTS At follow-up, QCA analysis revealed that lumen loss was significantly worse in BMS and in both LPD groups in comparison to BP-PES stents (P=.02). Histomorphometric analysis showed that the LPD500 group presented the highest percentage of area stenosis, achieving a statistically significant difference in comparison to BMS and BP-PES stents. CONCLUSION Our study demonstrates that local paclitaxel delivery using the Remedy transport catheter in the two studied doses (250 and 500 μg) is not effective at neointimal hyperplasia inhibition.