Significant aortic regurgitation after transfemoral aortic valve implantation: patients' gender as independent risk factor.

AIM: Significant aortic regurgitation (AR) has been reported in 20% of patients undergoing transfemoral aortic valve implantation (TAVI) and has been associated with increased mortality. Depending on the population included and the type of implanted prosthesis, several anatomical and procedural factors have been linked with increased risk of post-TAVI AR. While the impact of patients' gender on this complication, is still contradictory. We sought to assess the impact of patients' gender on the risk of significant AR after TAVI. METHODS: We included 323 consecutive patients (136 men) who underwent transfemoral implantation of either self-expandable or balloon-expandable prostheses for treatment of symptomatic aortic stenosis. RESULTS: After TAVI 52 patients (16.1%) had AR grade ≥ 2/4 as evaluated by angiography. They were more frequently male (59.6% vs. 40.4%, P = 0.005), received self-expandable (94.2% vs. 63.5%, P < 0.001) and bigger size prostheses (28 ± 1.9 vs. 27.3 ± 2.1 mm, P = 0.028) and had reduced left ventricular ejection fraction (45.3% ± 14.2% vs. 51.2% ± 13%, P = 0.003) compared to patients with AR grade < 2/4 (N. = 271). In multivariate analysis, men (OR 2.13 [95% CI, 1.08-4.18]) and prosthesis type (OR 13.17 [95% CI, 3.24-57.97]) were identified as independent predictors of AR grade ≥ 2/4. CONCLUSION: Alongside with the implantation of self-expandable aortic prosthesis, male gender independently increases the risk of significant AR in patients undergoing TAVI. The question if this finding is related to gender biology itself or to gender-related aggregation of subtle anatomic characteristics needs further investigations.

Omission of excisional therapy is associated with an increased risk of invasive cervical cancer after cervical intraepithelial neoplasia III.

BACKGROUND: Using data from the population-based Geneva Cancer Registry we evaluated the risk of invasive cervical cancer following carcinoma in situ (CIS) or cervical intraepithelial neoplasia (CIN) III according to type of treatment. METHODS: Included in the study were all women diagnosed with CIS/CIN III in Geneva (Switzerland) between 1970 to 2002 (n=2658) and followed for invasive cervical cancer occurrence until 31st December 2008. We calculated age and period standardised incidence ratios (SIR) and multiadjusted hazard ratios (HR) of invasive cervical cancer by treatment groups. RESULTS: During follow-up, 17 women developed invasive cervical cancer, conferring a SIR of 5.1 (95% confidence intervals [CI] 3.0-8.1). The risk of cervical cancer was significantly increased until 10 years after diagnosis. The risk was highest for women ≥ 50 years (SIR=7.3, 95% CI: 2.7-15.8) and for women who did not undergo excisional treatment (SIR=25, 95% CI: 12.0-46.0). The multiadjusted HR of invasive cervical cancer for women who did not undergo surgical excisional treatment was 9.4 (95% CI: 2.8-32.2) compared with women who did. CONCLUSION: Women diagnosed with CIS/CIN III are at increased risk of developing invasive cervical cancer. This risk is particularly high for women who did not have excision of cervical lesions.

[Targeted therapy in lung cancer: molecular testing using cytological specimens]. / Thérapies ciblées du cancer pulmonaire: tests moléculaires à partir d'échantillons cytologiques.

Important advances in lung cancer treatment have been made over the last decade. Several drugs designed to target molecular pathways involved in cancer-cell growth and survival have been shown to be effective in a selected fraction (<20%) of non-small cell lung cancer patients. Somatic mutations in several genes (i.e.: EGFR and KRAS) can predict patient's response to targeted therapies. Those mutations are commonly detected on histopathological samples (core-needle biopsy/ surgical resection). However, when tissue biopsies are not available, molecular testing has to be performed on cytological specimens. Issues raised by molecular testing on cytological specimen are discussed in this article.

[Fine needle aspiration of the thyroid: the value of on-site evaluation]. / Ponction à l'aiguille fine de la thyroïde: intérêts de l'évaluation cytologique immediate.

Thyroid nodules are very common in the general population and most of them are benign. Fine needle aspiration (FNA) of the thyroid is routinely used because it is a rapid, simple, accurate and cost-effective technique which allows the adequate selection of patients who should be managed surgically. However, the diagnostic yield of FNA is variable and depends of multiple factors including the one who performs FNA, the aspiration and cytological slide preparation techniques, and cytopathologist's experience. On-site evaluation of thyroid FNA material and close clinico-pathological collaboration offer many advantages and optimizes the yield of FNA.

Late adult onset of Langerhans cell histiocytosis mimicking glioblastoma multiforme.

Langerhans cell histiocytosis (LCH) with multiple organ involvement is a rare disorder in adults. Extrapituitary involvement of the central nervous system (CNS) is uncommon. We report the unusual case of a 55-year-old woman presenting with a left-sided hemiataxia-hemiparesis, left hemisensory loss and short-lasting episodes of an alien left hand due to lesions of the internal capsule and the right thalamus, extending into the mesencephalon associated with extensive surrounding edema, without pituitary involvement. The neuroradiological image suggested glioblastoma multiforme. Brain biopsy revealed inflammatory tissue and "pseudotumoral" multiple sclerosis was suspected. Biopsy of concomitant lung and bone lesions disclosed Langerhans cell histiocytosis. The treatment with pulsed steroids in association with mycophenolate mofetil led to a sustained, clinical neurological remission.

Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens.

OBJECTIVE: To identify in cytology, high-grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high-grade cervical intraepithelial lesion in histology. METHODS: Thirty-nine ThinPrep cervical smear (Pap) tests reported as AGC of undetermined significance and showing high-grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high-grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto-histological correlation was performed. RESULTS: A high frequency of diverse glandular pathologies coexisted with high-grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre-neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high-grade squamous intraepithelial lesions. CONCLUSIONS: Special efforts to recognize endocervical glandular extension in high-grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.

Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings.

OBJECTIVE: To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM). METHODS: Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy. RESULTS: The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells. CONCLUSION: The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).

Bronchoalveolar cytology for diagnosing pulmonary GVHD after bone marrow transplant in children.

BACKGROUND: Cytological composition of bronchoalveolar lavage (BAL) fluid in pediatric bone marrow transplant (BMT) recipients with pulmonary complications has not been comprehensively described and BAL specific markers of pulmonary GVHD are lacking. The aim of this retrospective study was to assess the role of BAL in the diagnosis of pulmonary GVHD by comparing BAL cytological findings between pediatric allogenic BMT patients with pulmonary complications and oncology children receiving chemotherapy alone. METHODS: Retrospective analysis of BAL specimens for cytology, total and differential cell counts and presence of infections. RESULTS: Seventeen BMT and 13 chemotherapy BAL were analyzed. BAL total cell count was increased but similar between groups (96.9 x 10(4) vs. 98.2 x 10(4), P = NS). BAL cellular composition differed considerably between groups with a significantly higher number of lymphocytes (18% vs. 6.25%, P = 0.03) and a significantly lower number of neutrophils (25.9% vs. 58%, P = 0.02) in BMT BAL specimens. Atypical epithelial cells were significantly more frequent (75% vs. 30.8%, P = 0.027), and significantly more severe (P = 0.01) in BMT patients. The presence and severity of atypia was not associated with infection or pneumotoxic drug exposure (P = NS). CONCLUSION: BAL cytology differs significantly between BMT and chemotherapy patients. The presence BAL lymphocytosis and severe epithelial cell atypia concomitantly to respiratory symptoms and GVHD in other organs may suggest the diagnosis of pulmonary GHVD. Prospective studies assessing the reliability of this finding combined with markers such as epithelial cell apoptosis and increased cytokines are needed.

Primary intrapulmonary thymoma: a systematic review.

AIM: This article reviews the literature on the clinical features, diagnosis and management of primary intrapulmonary thymoma. METHODS: Medline, Embase and Cochrane Library searches were performed on all relevant Anglo-Saxon language articles. The search words included "primary pulmonary thymoma" and "intrapulmonary thymoma". Secondary references were obtained from key articles. Prognostic and treatment strategies were analyzed by the Kaplan-Meier method, comparisons between curves were made using log rank test. RESULTS: The searches yielded 25 cases of primary intrapulmonary thymoma. Median follow-up was 9 months (1 day to 13 years). At follow-up, 14 patients were tumor free, one patient had a local recurrence 8 years after radiotherapy, one patient responded favorably to radiotherapy, six patients died and three patients were lost to follow-up. The presence of a paraneoplastic syndrome decreased survival (P=0.02), however, histological subgroup (P=0.216), clinical stage (P=0.63) and tumor size (P=0.288) did not affect survival. Survival in surgically managed patients was significantly better than in conservatively managed patients (P=0.039). Adjuvant radiotherapy did not provide any benefit (P=0.4). CONCLUSION: Complete resection of primary intrapulmonary thymomas appears sufficient in non-malignant tumors. Because of the risk of late local recurrence, long-term regular clinical follow-up is warranted.

A randomized trial comparing phosphorylcholine-coated stenting with balloon angioplasty as well as abciximab with placebo for restenosis reduction in small coronary arteries.

OBJECTIVE: The objective of this randomized trial was to assess the antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of abciximab in small coronary arteries when compared with percutaneous transluminal coronary angioplasty (PTCA) and placebo respectively. BACKGROUND: Stent coating with PC has been shown to reduce protein absorption and platelet activation which may reduce the risk of restenosis. Furthermore, on the basis of nondedicated studies abciximab is believed to reduce the risk of restenosis after coronary interventions. METHODS: A total of 502 patients with lesions situated in small coronary arteries (vessel diameter /=50% diameter stenosis) at follow-up; death or myocardial infarction, and target vessel revascularization (TVR), were assessed as secondary end-points. RESULTS: Angiographic restenosis did not differ between patients treated with PC-coated stents or with PTCA (39.0% vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3% vs. 34.3%; P = 0.29). Similarly, the need for TVR at 1-year follow-up did not differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P = 0.98) as well as between patients treated with abciximab or placebo (18.7% vs. 21.9%; P = 0.44). CONCLUSIONS: PC-coated stents and abciximab failed to reduce the incidence of angiographic restenosis after percutaneous coronary intervention of small coronary arteries. These data strengthen the belief that future studies on prevention of restenosis in small coronary arteries should focus on drug-eluting stents.

Development of a quantitative TaqMan RT-PCR for respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a ubiquitous RNA virus of the family Paramyxoviridae that may interfere with graft tolerance and with other interstitial lung diseases. The low viral titre observed in the immunodeficient transplanted patients requires a highly sensitive detection method. Although different tests already exist for the detection of RSV, reverse transcription-polymerase chain reaction (RT-PCR) has been shown to have the best sensitivity. In this study, a SYBR Green assay was established for the detection of RSV A and RSV B in a common screening test, and two quantitative TaqMan RT-PCRs were developed to quantify both RSV subgroups separately. Standard dilutions obtained from RSV cell infections were included in each test, and the assay was normalised using a housekeeping gene. RSV was found in 16% of the transplanted patients tested. The quantitative TaqMan assay is fast, reproducible, specific and very sensitive, and could facilitate considerably the detection of RSV virus. This would in-turn facilitate studies on the role of RSV in graft rejection.

Carcinoma arising in congenital lung cysts.

We report on a patient presenting with a bronchioloalveolar carcinoma fortuitously detected in the wall of a bronchogenic cyst. Evidence suggests that unstable epithelial cells contained within the cyst wall may lead to premalignant proliferation and neoplasia. In the current case, we demonstrated an increased proliferative activity in some areas of the cyst consistent with atypical adenomatous hyperplasia. Hence, we stress the importance of close follow-up of all suspected congenital lung cysts because of their potential malignant degeneration.

Incidence of thrombotic occlusion and major adverse cardiac events between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week ticlopidine regimen.

OBJECTIVES: We attempted to make a comprehensive assessment of the risk of stent failure (death, myocardial infarction or angiographically documented occlusion), differentiating early (first and second weeks) and late (third and fourth weeks) events. BACKGROUND: The risk of stent failure decreases rapidly within the first week. It has been suggested that the risk rate for late events is close to 0% and that the thienopyridine regimen (ticlopidine or clopidogrel) could be safely reduced from four to two weeks, minimizing the risk of hematological complications. METHODS: We analyzed 5,678 patients with successful coronary stent placement and a four-week ticlopidine regimen. RESULTS: The rate of stent failure was 2.5% at four weeks, with 112 early (2.0%) and 30 late events (0.5%). Multivariate analysis identified different risk factors for early versus late events. While variables on stenosis severity and procedural results that can be influenced by the operator were identified as independent risk factors for early events (percent stenosis before and after the procedure, residual dissection, length of stented segment), more clinical variables were associated with late events (age, reduced left ventricular function, systemic hypertension as a protective factor). The late-event rate was <0.1% in the absence of these factors, but it was 2.5% with all three risk factors present. CONCLUSIONS: The risk of late stent failure is low with a four-week ticlopidine regimen. However, high-risk subgroups have a risk of 2.5%. As this rate is presumably higher if thienopyridines are discontinued after two weeks, these data suggest that a risk stratification to a two- or four-week regimen is preferable to a general reduction.

Fungal infections in transplant recipients.

Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores of both fungi that are "pathogenic" even in the normal host, such as Cryptococus neoformans, and those that are "opportunistic", such as Candida and Aspergillus species, among others. Although these latter species may occasionally form fungal balls or induce allergic phenomena in the normal host, they produce more invasive diseases in immunosuppressed patients. Among these diseases, pseudomembranous aspergillosis has recently been described. The diagnostic approach to these entities, and, in particular, the thin dividing line between colonization and infection are addressed, along with the diagnostic value of the various procedures. New prophylactic regimens are reviewed such as the possibility of using amphotericin aerosols in combination with systemic azole administration. The authors would emphasize the importance of restoring lung defences by not only decreasing immunosuppressive regimens but also considering the use of newly available recombinant cytokines such as growth factors, to reduce neutropenia, for instance, in addition to antifungal drugs when infection is diagnosed. However, immunomodulation procedures are far from being well established.

Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease.

OBJECTIVE: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue--mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT--with follow-ups averaging two years (0.5-8)--are receiving thyroxin substitution. CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.

Role of the distal balloon protection technique in the prevention of cerebral embolic events during carotid stent placement.

BACKGROUND AND PURPOSE: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. METHODS: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. RESULTS: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017). CONCLUSIONS: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.

Sustained benefit over four years from an initial combined antiplatelet regimen after coronary stent placement in the ISAR trial. Intracoronary Stenting and Antithrombotic Regimen.

Combined antiplatelet therapy after coronary stent placement is superior to anticoagulation with respect to early outcome. It is unclear if this benefit is maintained during long-term follow-up. This study reports on the 4-year clinical outcome of patients randomized in the Intracoronary Stenting and Antithrombotic Regimen trial. In the Intracoronary Stenting and Antithrombotic Regimen trial, 517 patients were randomized after successful placement of Palmaz-Schatz stents: 257 to aspirin and ticlopidine, and 260 to aspirin and phenprocoumon. Ticlopidine and phenprocoumon were given for 4 weeks. At 30 days, patients with ticlopidine had significantly fewer adverse cardiac events (1.6% vs 6.2%; p = 0.007), nonfatal myocardial infarction (0.8% vs 3.5%; p = 0.034), and target vessel revascularization procedures (1.2% vs 5.4%; p = 0.007). At 4 years, rates for any adverse cardiac events were 22.6% versus 28.5% (p = 0.078), for nonfatal myocardial infarction 0.9% versus 5.8% (p = 0.003), and for target vessel revascularization 18.3% versus 22.7% (p = 0.21). The absolute difference in event rates (4.6% after 30 days) was maintained after 4 years (5.9%). Event rates beyond day 30 were not significantly different (21.1% vs 22.5%; p = 0.78), nor were the rates beyond the first year, which were very low (5.2% vs 3.6%; p = 0.50). This study shows that the benefit of combined antiplatelet therapy evident after 30 days is maintained after 4 years. Independent of the initial regimen, rates of adverse cardiac events are low beyond the first year.

Restenosis after coronary placement of various stent types.

Coronary stent implantation is being performed in an increasing number of patients with a wide spectrum of clinical and lesion characteristics. A variety of stent designs are now available and continuous efforts are being made to improve the stent placement procedure. The objective of this study was to perform a comprehensive analysis of the relation between clinical, lesion, and procedural factors, and restenosis after intracoronary stenting in a large and unselected population of patients. A consecutive series of 4,510 patients with coronary stent placement was analyzed. Exclusion criteria were only a failed procedure and an adverse outcome within the first month after the intervention. Follow-up angiography was performed in 80% of patients at 6 months. Clinical, lesion, and procedural data from all 3,370 patients (4,229 stented lesions) with follow-up angiography were analyzed in a logistic regression model for restenosis (> or =50% diameter stenosis). Clinical factors contributed to the predictive power of the model much less than lesion and procedural factors. The strongest risk factor for restenosis was a small vessel size, with a 79% increase in the risk for a vessel of 2.7 mm versus a vessel of 3.4 mm in diameter. Stent design was the second strongest factor; the incidence of restenosis ranged from 20.0% to 50.3% depending on the stent type implanted. In conclusion, this study demonstrates the predominant role of lesion and procedural factors in determining the occurrence of restenosis after coronary stent placement. Among these factors, stent design appears to play a particularly important role in the hyperplastic response of the vessel wall.