VT ablation based on CT imaging substrate visualization: results from a large cohort of ischemic and non-ischemic cardiomyopathy patients.

INTRODUCTION: The eradication of ventricular tachycardia (VT) isthmus sites constitutes the minimal procedural endpoint for VT ablation procedures. Contemporary high-resolution computed tomography (CT) imaging, in combination with computer-assisted analysis and segmentation of CT data, facilitates targeted elimination of VT isthmi. In this context, inHEART offers digitally rendered three-dimensional (3D) cardiac models which allow preoperative planning for VT ablations in ischemic and non-ischemic cardiomyopathies. To date, almost no data have been collected to compare the outcomes of VT ablations utilizing inHEART with those of traditional ablation approaches. METHODS: The presented data are derived from a retrospective analysis of n = 108 patients, with one cohort undergoing VT ablation aided by late-enhancement CT and subsequent analysis and segmentation by inHEART, while the other cohort received ablation through conventional methods like substrate mapping and activation mapping. The ablations were executed utilizing a 3D mapping system (Carto3), with the mapping generated via the CARTO® PENTARAY™ NAV catheter and subsequently merged with the inHEART model, if available. RESULTS: Results showed more successful outcome of ablations for the inHEART group with lower VT recurrence (27% vs. 42%, p < 0.06). Subsequent analyses revealed that patients with ischemic cardiomyopathies appeared to derive a significant benefit from inHEART-assisted VT ablation procedures, with a higher rate of successful ablation (p = 0.05). CONCLUSION: Our findings indicate that inHEART-guided ablation is associated with reduced VT recurrence compared to conventional procedures. This suggests that employing advanced imaging and computational modeling in VT ablation may be valuable for VT recurrences.

The effect of intraparenchymal blood patching on the rate of pneumothorax in patients undergoing percutaneous CT-guided core biopsy of the lung.

PURPOSE: To assess the effect of intraparenchymal blood patching (IBP) as well as tumor- and operator-related risk factors on the rate of pneumothoraxes after percutaneous CT-guided core needle biopsy of the lung. MATERIALS AND METHODS: We performed a retrospective analysis of 868 CT-guided lung biopsies that were conducted at our institution between 2003 and 2018, of which 419 (48%) received an IBP. Outcome variable included the rates of pneumothorax and chest tube placement, as well as lesion size (<3 cm versus ≥3 cm long axis diameter), lesion depth (≤2 cm, >2-4 cm, >4-5 cm and >5 cm distance to the pleura), location within the lungs (upper lobe, lower lobe, middle lobe), needle caliber (13 G, 15 G, 17 G, 19 G), number of samples taken (1-3 versus ≥4 samples), and experience of the performing physician. RESULTS: The rate of pneumothorax was significantly (p < 0.05) lower in the group with IBP (10.7%) compared to the group without IBP (15.4%). The number of post-interventional chest tube placements was also lower in the IBP group (3.1% vs. 5.8%) but not statistically significant. The lesion size correlated negatively with the rate of pneumothoraxes, whereas in both groups (±IBP) lesions ≥ 3 cm showed a significantly lower rate of pneumothorax (p < 0.05). With increasing lesion depth, the pneumothorax rate increased with (p < 0.01) and without (p < 0.001) IBP. The rate of pneumothorax was significantly lower (p < 0.05) for 17 G needles with IBP, but not for other calibers. For biopsies in the lower lobe, the pneumothorax rate reduced significantly (p < 0.001) with IBP. In case of ≥4 tissue samples, the pneumothorax rate was significantly lower with IBP (p < 0.01). For experienced operators, the overall pneumothorax rate was significantly lower compared to less experienced operators (p < 0001). CONCLUSIONS: IBP significantly reduces the rate of pneumothorax following CT-guided lung biopsies in particular for lesions located deeper in the lungs, when ≥4 samples are taken, when samples are taken by less-experienced operators, and when sampling from the lower lobes.

Repeat ablation for paroxysmal atrial fibrillation - Does adenosine play a role in predicting pulmonary vein reconnection patterns?

BACKGROUND: Pulmonary vein (PV) reconduction after PV isolation (PVI) unmasked by adenosine is associated with a higher risk for paroxysmal atrial fibrillation (PAF) recurrence. It is unknown if the reconnected PVs after adenosine testing and immediate re-ablation can predict reconnection and reconnection patterns of PVs at repeat procedures. We assessed reconnection of PVs with and without dormant-conduction (DC) during the first and the repeat procedure. METHODS: We included 67 patients undergoing PVI for PAF and a second procedure for PAF recurrence. DC during adenosine administration at first procedure was seen in 31 patients (46%). 264 PVs were tested with adenosine; DC was found in 48 PVs (18%) and re-ablated during first procedure. During the second procedure, all PVs where checked for reconnection. RESULTS: Fifty-eight patients (87%) showed PV reconnection during the second procedure. Reconnection was found in 152/264 PVs (58%). Of 216 PVs without reconnection during adenosine testing at the first ablation, 116 PVs (53.7%) showed reconnection at the repeat procedure. Overall, 14.9% of patients showed the same PV reconnection pattern in the first and second procedure, expected statistical probability of encountering the same reconnection pattern was only 6.6%(p = 0.012). CONCLUSIONS: In repeat procedures PVs showed significantly more often the same reconnection pattern as during first procedure than statistically expected. More than 50% of initial isolated PVs without reconnection during adenosine testing showed a reconnection during repeat ablation. Techniques to detect susceptibility for PV re-connection like prolonged waiting-period should be applied. Elimination of DC should be expanded from segmental to circumferential re-isolation or vaster RF application.

Endometrial cells in liquid-based cervical cytology: a diagnostic pitfall solved by preparing cytohistology from the residual thin layer sample.

OBJECTIVE: It was our aim to assess the usefulness of cytohistology in cervical thin layer brush samples with problems in the differential diagnosis of endometrial cells. STUDY DESIGN: This study reveals the cytological, cytohistological and immunohistochemistry findings of 8 cases suspicious of adenocarcinoma in situ (AIS)/adenocarcinoma (AC) in cervical liquid-based cytology (LBC) preparations that turned out to be normal endometrial cells. RESULTS: All 8 cervical LBCs featured endometrial and atypical endocervical-like columnar cells with frequent ragged 'feathered' edge appearance and rosette formations. Overlapping atypical glandular cell groups were present on 2 ThinPrep slides as well. In cytohistology of 7 cases, the recognition of endometrial stroma with endometrial glands easily allowed the diagnosis of normal endometrium. In 1 case with very small loose tissue fragments without glands, the diagnosis could be established by positivity for CD10 marker (endometrial stroma) and without proliferative activity in the Ki-67 immunostaining. CONCLUSION: In cervical LBC preparations, nuclear hyperchromasia, pleomorphism and nucleoli in normal endometrial cells are more obvious than in conventional smears, and their arrangement is sometimes suggestive of AIS or AC. In the 8 cases presented, we could avoid a false-positive diagnosis of AIS or AC through cytohistology/immunohistochemistry, and in consequence, unnecessary colposcopical/histological examination.

Increased diagnostic accuracy of atypical glandular cells in cervical liquid-based cytology using cell blocks.

OBJECTIVE: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). METHODS: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid-based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex-Brush(®) Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock(®)) stained with Papanicolaou and immunostaining. RESULTS: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC-favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC-NOS and in two of seven with AGC-FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. CONCLUSIONS: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC-FN, AIS and adenocarcinoma.

The Thomson deflectometer: a novel use of the Thomson spectrometer as a transient field and plasma diagnostic.

Laser accelerated proton beams have been used for field characterization in expanding plasmas. The Thomson parabola spectrometer, as a charged particles analyzer, also allows precise measurement of the charged particles' trajectories. The proton's deflections by fast changing plasma fields can be measured with the new design of the Thomson parabola spectrometer and, therefore, it can be applied for proton deflectometry. It is shown that from resulting spectrograms the plasma field dynamics can be reconstructed with high temporal resolution. In a proof-of-principle experiment, a weakly relativistic plasma expansion is studied as an example.

Quasimonoenergetic deuteron bursts produced by ultraintense laser pulses.

We report on the generation and laser acceleration of bunches of energetic deuterons with a small energy spread at about 2 MeV. This quasimonoenergetic peak within the ion energy spectrum was observed when heavy-water microdroplets were irradiated with ultrashort laser pulses of about 40 fs duration and high (10(-8)) temporal contrast, at an intensity of 10(19) W/cm(2). The results can be explained by a simple physical model related to spatial separation of two ion species within a finite-volume target. The production of quasimonoenergetic ions is a long-standing goal in laser-particle acceleration; it could have diverse applications such as in medicine or in the development of future compact ion accelerators.

Double chirped-pulse-amplification laser: a way to clean pulses temporally.

We demonstrate a double chirped-pulse-amplification (CPA) Ti: sapphire laser system that includes two CPA stages with intermediate nonlinear temporal pulse filtering. The method makes it possible to reduce substantially the background of amplified spontaneous emission (ASE), including prepulses and postpulses. An ASE temporal contrast of 10(10) was demonstrated at 20 mJ of output energy and 50-fs pulse duration. The demonstrated scheme is applicable to petawatt power-level laser systems.

Spectral dips in ion emission emerging from ultrashort laser-driven plasmas.

Deep dips in MeV ion spectra are obtained from water droplet targets irradiated by intense [(0.5-1.2) x 10(19) W/cm(2)] and ultrashort (35 fs) laser pulses. The existence of these dips is ascribed to the generation of a multielectron-temperature plasma, which is confirmed by our experiments. An existing fluid model based on hot-electron components with significantly different temperatures is consistent with the behavior we observe in the ion spectra of the femtosecond laser-driven interaction. The model provides a good simulation of the observed spectral dips and allows us to establish important parameters such as hot- and cold-electron temperatures and the respective electron density ratios. The result may be of interest for spectral tailoring of proton spectra in future applications of laser-generated proton beams.

Characterization of a nonlinear filter for the front-end of a high contrast double-CPA Ti:sapphire laser.

A nonlinear filter using rotation of the polarization ellipse in air is investigated. Scheme to enhance the temporal contrast is developed for a double-CPA multi-terawatt Ti:sapphire laser. It supports an energy level of millijoule and has a high efficiency. The method allows suppression of the ASE pedestal, pre- and post-pulses by 3 orders of magnitude and also steepens the pulse front. For the physical interpretation of the results, numerical simulation of the filtering is performed.

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia.

We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study 184 women treated for CIN 2 or 3 were prospectively monitored by cervical cytology and high-risk HPV testing 3, 6, 9, 12 and 24 months after treatment. Post-treatment CIN 2/3 was present in 29 women (15.8%). A positive high-risk HPV test 6 months after treatment was more predictive for post-treatment CIN 2/3 than abnormal cervical cytology (sensitivity 90% and 62% respectively, with similar specificity). At 6 months the negative predictive value of a high-risk HPV negative, normal smear, was 99%. Largely overlapping, partly different groups of women with post-treatment CIN 2/3 were identified by HPV testing and cervical cytology. Based on these results we advocate to include high-risk HPV testing in monitoring women initially treated for CIN 2/3. In case of a high-risk HPV positive test or abnormal cervical cytology, colposcopy is indicated. All women should be tested at 6 and 24 months after treatment and only referred to the population-based cervical cancer screening programme when the tests are negative on both visits.

PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes.

BACKGROUND/AIMS: To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes. METHODS: A cohort of 2250 women, 34-54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status. RESULTS: Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status. CONCLUSION: High risk HPV testing is superior to neural network based screening in identifying women at risk of developing CIN III. For women with normal cytology and borderline changes and a negative high risk HPV test, the screening interval can be considerably prolonged.

Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study.

BACKGROUND: A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening. METHODS: We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer. FINDINGS: 33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21-59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear. INTERPRETATION: Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high-risk human papillomavirus DNA.

In this study, we investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in the spectrum of cervical premalignant lesions. Reconstruction experiments revealed that telomerase activity determined by the telomeric repeat amplification protocol assay and hTERT mRNA by reverse transcriptase-PCR could be detected in down to 100 and 1 SiHa cervical cancer cells, respectively. Telomeric repeat amplification protocol analysis on cervical tissue specimens revealed that none of the histomorphologically normal cervical samples (n = 8) and cervical intraepithelial neoplasia (CIN) grade I (n = 10) and grade II (n = 8) lesions had detectable telomerase activity. However, telomerase activity was shown in 40% of CIN grade III lesions (n = 15) and 96% of squamous cell carcinomas (n = 24). Despite the fact that hTERT mRNA was found at much higher frequencies, semiquantitative reverse transcriptase-PCR revealed that elevated hTERT mRNA levels were strongly correlated with detectable telomerase activity. Furthermore, telomerase activity and elevated hTERT mRNA levels were only detected in cases that contained high-risk HPV DNA. In contrast, low or undetectable hTERT mRNA levels were demonstrated in both high-risk HPV positive and negative cases. These data indicate that telomerase activity detectable with the assay used and concomitant elevated levels of hTERT mRNA reflect a rather late step in the CIN to squamous cell carcinoma sequence, which follows infection with high-risk HPV.

Well-differentiated papillary mesothelioma of the peritoneum: a separate entity.

Three female patients with a diffuse well-differentiated papillary mesothelioma of the peritoneum are presented. They did not have a history of exposure to asbestos. The peritoneal biopsies were studied extensively, including electron microscopy, nuclear morphometry and DNA ploidy analysis. The results from these more sophisticated investigations confirmed the mesothelial origin and further characterised these lesions. One of the 3 patients has continuing elevated serum CA-125 levels, which increased transiently during and after pregnancy. All 3 patients have done well without therapy, 2 patients being alive and non-symptomatic 6 and 7 years after the initial diagnosis. It is important to distinguish this disorder from the malignant diseases of the peritoneum and the ovary. In view of the indolent course of this subtype of mesothelioma, avoidance of treatment is justified unless there is evidence of progressive disease.

Chlamydia trachomatis and ectopic pregnancy: retrospective analysis of salpingectomy specimens, endometrial biopsies, and cervical smears.

AIMS: To examine the role of Chlamydia trachomatis in ectopic pregnancy by detection of DNA in archival salpingectomy specimens, and in their preceding cervical specimens and endometrial biopsies, by using the polymerase chain reaction (PCR). METHODS: Archival paraffin embedded salpingectomy tissues (n = 48) from 37 women with ectopic pregnancy were examined for the presence of C trachomatis plasmid and omp1 DNA by PCR. In addition, preceding cervical specimens (n = 58) stored either as cervical cell suspensions or as archival cervical smears, and preceding endometrial biopsies (n = 18), taken 0-5.8 years before the ectopic pregnancy, were examined by PCR for the presence of C trachomatis. RESULTS: C trachomatis DNA was detected in only one of the 48 salpingectomy specimens from 37 women. However, in six of the 37 women, C trachomatis DNA was detected in the genital specimens (cervix and/or endometrial) taken before salpingectomy. C trachomatis infections were mostly found in endometrial or cervical specimens taken more than three years before ectopic pregnancy. No chlamydial DNA was found in endometrial or cervical specimens taken at the same time of the ectopic pregnancy. CONCLUSIONS: Although no C trachomatis DNA was found in salpingectomy specimens, several women with ectopic pregnancy had C trachomatis infections in endometrial and cervical specimens in the past. This suggests that at least in these cases the ectopic pregnancy is a late post-inflammatory complication of an ascending C trachomatis infection resulting in a scarred fallopian tube.

Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer.

AIM: To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS: Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design. RESULTS: HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens. CONCLUSIONS: The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.