Effect of unidirectional airflow ventilation on surgical site infection in cardiac surgery: environmental impact as a factor in the choice for turbulent mixed air flow.

BACKGROUND: Surgical site infection (SSI) in the form of postoperative deep sternal wound infection (DSWI) after cardiac surgery is a rare, but potentially fatal, complication. In addressing this, the focus is on preventive measures, as most risk factors for SSI are not controllable. Therefore, operating rooms are equipped with heating, ventilation and air conditioning (HVAC) systems to prevent airborne contamination of the wound, either through turbulent mixed air flow (TMA) or unidirectional air flow (UDAF). AIM: To investigate if the risk for SSI after cardiac surgery was decreased after changing from TMA to UDAF. METHODS: This observational retrospective single-centre cohort study collected data from 1288 patients who underwent open heart surgery over 2 years. During the two study periods, institutional SSI preventive measures remained the same, with the exception of the type of HVAC system that was used. FINDINGS: Using multi-variable logistic regression analysis that considered confounding factors (diabetes, obesity, duration of surgery, and re-operation), the hypothesis that TMA is an independent risk factor for SSI was rejected (odds ratio 0.9, 95% confidence interval 0.4-1.8; P>0.05). It was not possible to demonstrate the preventive effect of UDAF on the incidence of SSI in patients undergoing open heart surgery when compared with TMA. CONCLUSION: Based on these results, the use of UDAF in open heart surgery should be weighed against its low cost-effectiveness and negative environmental impact due to high electricity consumption. Reducing energy overuse by utilizing TMA for cardiac surgery can diminish the carbon footprint of operating rooms, and their contribution to climate-related health hazards.

The history of transcatheter aortic valve implantation: The role and contribution of an early believer and adopter, the Netherlands.

This paper describes the history of transcatheter aortic valve implantation (TAVI) from its preclinical phase during which visionary pioneers developed its concept and prototype valves against strong head wind to first application in clinical practice (2002) and the clinical and scientific role of an early believer and adopter, the Netherlands (2005).

Treatment decision for transcatheter aortic valve implantation: the role of the heart team : Position statement paper of the Dutch Working Group of Transcatheter Heart Interventions.

The current paper presents a position statement of the Dutch Working Group of Transcatheter Heart Valve Interventions that describes which patients with aortic stenosis should be considered for transcatheter aortic valve implantation and how this treatment proposal/decision should be made. Given the complexity of the disease and the assessment of its severity, in particular in combination with the continuous emergence of new clinical insights and evidence from physiological and randomised clinical studies plus the introduction of novel innovative treatment modalities, the gatekeeper of the treatment proposal/decision and, thus, of qualification for cost reimbursement is the heart team, which consists of dedicated professionals working in specialised centres.

Percutaneous Decannulation of Femoral Venoarterial ECMO Cannulas Using MANTA Vascular Closure Device.

Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the treatment of refractory cardiac arrest and postarrest cardiogenic shock. We propose a technique for percutaneous decannulation of femoral venoarterial ECMO cannulas by using the MANTA vascular closure device, designed to close large-bore arteriotomies. This technique significantly simplifies the decannulation and might diminish the potential complications caused by the standard surgical removal.

Reproducibility and efficiency testing of two sampling methods for image analysis in cytology.

OBJECTIVE: Quantitative nuclear DNA analyses and nuclear morphometry have become a widely used tool in pathology. Nevertheless, studies done by different observers utilizing the same methods very often have shown different results. One of the reasons could be that different sampling methods were used. In this study two selection methods for image analyses (the consecutive selection method and the random selection method) were tested for reproducibility and efficiency. STUDY DESIGN: Using an interactive imaging analysis system, 10 cases (5 breast adenocarcinomas, 3 prostatic cancers, 1 sarcoma, 2 prostatic hyperplasias) were measured twice by using each sampling method. Median nuclear area and entropy (i.e., a statistical descriptor of DNA histograms) were the parameters calculated. RESULTS: The results showed that using the consecutive selection method, the number of individual nuclei in a cytologic sample that should be measured to obtain reproducible results was 150 for nuclear area and 110 for entropy. The corresponding figures using random systematic selection method were 80 for assessment of nuclear area and 100 for assessment of entropy. CONCLUSION: Both methods showed high reproducibility and a good correlation with each other. The mathematical idea of "plateau values," which was used to estimate the number of measurements needed, was considered a good contribution to increasing the efficiency of both methods.

Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer.

Tumorigenesis of colorectal cancer in patients with hereditary non-polyposis colorectal cancer (HNPCC) has been postulated to follow a different pathway from that of sporadic colorectal tumors. A characteristic of HNPCC-associated tumors is the replication error phenotype. We studied tumorigenesis in 8 fresh-frozen and 67 paraffin-embedded colorectal tumors derived from 29 families with HNPCC or a familial aggregation of colorectal cancer. By using intragenic markers, inactivation of the wild-type allele of hMLH1 was shown to occur through loss of heterozygosity and not through a somatic point mutation. Microsatellite instability is very common and occurs early in almost all colorectal tumors from HNPCC patients. Transforming growth factor beta type II receptor (T beta RII) mutations occur in these tumors at a high frequency. Of colorectal cancers from families with HNPCC, 63% have frameshift mutations in T beta RII, compared with 10% of sporadic colorectal cancers. APC and K-RAS mutations appear to be as frequent in the HNPCC tumors as in the sporadic counterpart.

p53, Ki-ras, and DNA ploidy in human pancreatic ductal adenocarcinomas.

Ki-ras mutations and DNA aneuploidy are common findings in human pancreatic ductal adenocarcinomas. An altered p53 tumor-suppressor gene has been suggested to cooperate with activated Ki-ras in malignant cellular transformation and could enhance genomic instability. We have investigated a panel of well-documented pancreatic carcinomas with defined ploidy and Ki-ras mutations for the presence and pattern of genetic alterations of the p53 gene, their coincidence with Ki-ras point mutations, and their correlation with DNA ploidy, tumor pathology, and clinical course. DNA was isolated from formalin-fixed and paraffin-embedded tumor tissue and polymerase-chain-reaction-amplified fragments of the p53 gene exons 5 to 9 were screened by the single-strand conformation polymorphism method. The positive cases were further examined for mutations by direct sequencing. Twenty-nine of seventy-one (41%) tumors showed mutations of the p53 gene, however, five tumors carried two mutations resulting in a total of 34/71 (48%) genetic alterations of the p53 gene. The majority were missense point mutations and distributed primarily within the evolutionary conserved domains (62%). Ten of Thirty-four (29%) affected the hotspot codons 248, 273, and 282, respectively, and 21/34 (62%) of the p53 gene mutations clustered on exons 7 and 8. Transitions (71%) predominated over transversions (15%), deletions were identified in 7/34 (21%) tumors. One third of the carcinomas showed both Ki-ras codon 12 and p53 gene mutations. p53 mutations correlated with distant metastasis (p < 0.05) and survival (p < 0.05). DNA triploidy was associated with a mutated Ki-ras gene (p < 0.05) as well as with double mutations of c-Ki-ras and p53 (p < 0.05). Unlike most other malignant tumors pancreatic ductal adenocarcinomas exhibit a significantly higher incidence of c-Ki-ras than p53 gene mutations. However, like other neoplasms p53 gene mutations seem to be associated with a metastatic phenotype possibly acquired during tumor progression.

Genetic rearrangements in sporadic and familial gastric carcinomas detected with microsatellite markers.

Ten gastric carcinomas were studied for loss of heterozygosity by analysis of 21 microsatellite markers from 14 different chromosomes. Four patients had a family history of gastro-intestinal cancer, and six tumours were considered sporadic. We also studied a new mechanism in tumourigenesis recently reported in hereditary non polyposis colon cancer, a defect in mismatch repair that is seen as gain of new bands by the use of dinucleotide repeat markers. Loss of heterozygosity was detected with two markers in one primary tumour and with the majority of markers in one metastasis from a sporadic gastric tumour. Gain of microsatellite bands was seen in one tumour from a gene carrier in a family with hereditary non-polyposis colon cancer and in one sporadic tumour. Two tumours from patients with a family history of gastric cancer showed no rearrangements. Our results suggest that different types of genes are involved in initiation and progression of gastric cancer in sporadic and familial gastric cancer.

Morphometric characteristics in adenocarcinoma of the pancreas and chronic pancreatitis.

BACKGROUND: Morphometric analysis whereby size and form of cellular nuclei are transformed into quantities has previously been shown to be a valuable adjunct to the histopathologic differential diagnosis between chronic pancreatitis and pancreatic carcinoma. The present study aims to assess the clinical value of morphometry performed on cytologic material from benign and malignant pancreatic lesions. METHODS: Cytologic specimens from 100 patients with the diagnosis of pancreatic carcinoma and 15 patients with chronic pancreatitis were evaluated by interactive morphometry using a digital image analyzer system. RESULTS: There were significant differences (p < 0.001) for all morphometric variables between the malignant and benign groups (mean area p 50, 135.41 microns 2 versus 69.66 microns 2; anisokaryosis, 0.74 versus 0.41; and polymorphism, 0.13 versus 0.09). CONCLUSIONS: Morphometry may be used as a complementary tool in the cytologic diagnosis of pancreatic carcinoma.

The prognostic value of nuclear roundness and neopterin in ovarian cancer.

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours.

Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients.

Morphometry and prognosis in cancer of the pancreatic head.

The histological slides of 39 cases of cancer of the pancreatic head were analysed using an interactive image analyser system. Some 14 cases were classified as periampullary, 25 as ductal pancreatic cancer. All cases had undergone radical tumor resection according to Whipple's procedure. Morphometric data, tumor size and metastatic nodal involvement were correlated to prognosis. Univariate statistical analysis showed that the classical differentiation between ductal and periampullary cancer was a weaker prognosticator than morphometric variables. In fact, multivariant statistical analysis showed that the morphometric variable irregularity was the best prognosticator (p = 0.0001). No other variable added significant prognostic information. Irregularity is a newly developed variable describing the nuclear shape corrected for roundness. We conclude that morphometry can be of essential prognostic information for the clinician in cancer of the pancreatic head.

Discrimination of pancreatic adenocarcinomas from chronic pancreatitis by morphometric analysis.

Chronic pancreatitis and pancreatic ductal adenocarcinoma show similar gross and microscopic anatomical features. Morphological examination alone is not always sufficient in diagnostic practice to make the clinically important discrimination between these two entities. Cases of pancreatic tumors were analysed in a morphometric study to evaluate the discriminatory value of nuclear and nucleolar features. Histologic sections of pancreas from 18 cases of chronic pancreatitis and 33 cases of ductal adenocarcinoma were included either into a learning or a test set. A multivariable discriminatory rule was derived from the learning set of 23 cases including nuclear polymorphism and nucleolar density. When applied to the test set, all 28 cases of adenocarcinomas and chronic pancreatitis were correctly classified. Distributional features describing nucleolar density and variation in nuclear size and shape were the most efficient discriminatory variables. Morphometry is shown to be a simple and fast cell analytical method which can support clinical judgement in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma.

Investigation of nuclear c-MYC oncoprotein expression in human hematopoiesis: suitability of a rapid and reliable semiquantitative evaluation system.

The biologic functions mediated by the nuclear protooncogene, c-MYC are correlated to gene dosage. Since automated quantification programs are expensive, time-consuming and not easily available, and since analysis by flow cytometry is difficult in the case of nuclear antigens, we examined the suitability and reproducibility of a semiquantitative in situ evaluation system. This system was based on the percentage of nuclear area staining positively, and comprised the following categories: 0: negative, 1+: single scattered grains of the immunocytochemical staining product, 2+: confluence of grains to patches but less than 50% nuclear area positive, and 3+: greater than 50% positive nuclear area. In addition, sensitivity and specificity of two anti-c-MYC antibodies were investigated. Although both antibodies differed slightly in staining pattern and sensitivity, the four quantification categories were applicable for immunostainings of both antisera and highly reproducible when re-evaluated by the same observer (r = 0.98; p = 0.0001) or a second investigator (rAb155 = 0.98, rAb DCPm = 0.96; p = 0.0001), both reading blindly and independently. Comparing our semiquantitative evaluation categories and results of computer-assisted image analysis, the percentage of positive nuclear area (p less than 0.0001), the median staining intensity (p less than 0.0001), and the product of both (p less than 0.0001) differed significantly in the four evaluation categories. This result still held true after correction for nuclear size, which differed appreciably in various cell types (p less than 0.0001). The product of positive nuclear area, staining intensity and nuclear size (microns 2), which best approximates the absolute amount of c-MYC within a certain cell, was clearly different within the four staining categories (p less than 0.0001) and did not depend on cellular morphology within the staining categories 0 to 2. Also, the immunocytochemical technique proved highly reproducible (median day/day variance 0.65% (0-13); r = 0.995). The practicability of this system for semiquantification was demonstrated by (a) correlation of H score values of immunocytochemical stainings with densitometric scans of Western blots and (b) by the fact that peripheral blood lymphocytes, Phytohemagglutinin stimulated blasts, 13 cases of multiple myeloma and HL-60 cells differed concerning their estimated c-MYC amounts (p = 0.0125). This confirms on the effector molecule level results previously reported from mRNA in situ and Northern blotting analyses. We conclude that a simple and highly reproducible evaluation system can be used for in situ comparison of nuclear oncogene dosage.

Surface immunoglobulin density in the differential diagnosis of B-cell chronic lymphocytic leukemia and leukemic immunocytoma.

Using flow cytometry peripheral blood samples of 37 consecutive patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 consecutive patients with leukemic immunocytoma (IC) were studied in order to determine quantitative differences in the surface immunoglobulin (slg) density. In 8/37 (21.6%) cases of B-CLL and 1/17 (5.9%) cases of IC slg staining remained in the control level. Analysis of slg-positive cases demonstrated a close association between the amount of slg and diagnosis: per case the mean calculated fluorescence intensity for IC lymphocytes was 209.7 arbitrary linear intensity units (IU) (median: 156.4, standard error of the mean (SEM): 53.7) and for B-CLL lymphocytes 10.8 IU (median: 7.3, SEM: 1.1; p less than 0.0001). Altogether, 94.6% of all B-CLL patients and 76.5% of all IC patients were correctly classified when a cut-off point was fixed at a mean fluorescence intensity value of 20.0 IU. The percentage of leukemic cells as characterized by CD19 and HLA-DR reactivity was significantly lower in cases of IC (p less than 0.03 and p less than 0.01, respectively). In both entities disease progression occurred more frequently in advanced stages (II-IV) according to the Rai classification (p less than 0.01). In progressive disease rather than in stable disease circulating T lymphocytes were shown to express decreased amounts of surface CD3 antigen (p less than 0.02). We conclude that the quantitative assessment of surface antigens in addition to their qualitative characterization provides accurate information. In particular, the diagnostic discrimination between B-CLL and IC may be improved by determining the lymphocytes' slg amount.

Quantitative nuclear DNA content in fine needle aspirates of pancreatic cancer.

The quantitative nuclear DNA content of nuclei from fine needle aspirations from 70 patients with pancreatic cancer was measured using an image analyser system. Retrospective analysis of patients indicated that cases with tumour stemlines in the diploid region had the best chance for radical surgery (p less than 0.006) and the best probability of survival (p less than 0.0004). The prognosis for patients with tetraploid stemlines was intermediate and was poorest for patients with no stemlines in the diploid-tetraploid region. From those parameters assessed postoperatively, only the tumour stage added appreciable information on prognosis to the preoperative quantitative DNA content obtainable. Therefore, in patients with pancreatic cancer the quantitative DNA content should be taken into account in planning treatment and assessing prognosis. Furthermore, the quantitative DNA content may have a major role in stratification for further treatment trials.