Can the dynamic spectral imaging (DSI) color map improve colposcopy examination for precancerous cervical lesions? A prospective evaluation of the DSI color map in a multi-biopsy clinical setting.

BACKGROUND: Colposcopy serves as a subjective examination of the cervix with low sensitivity to detect cervical intraepithelial dysplasia (CIN) grade 2 or worse (CIN2 +). Dynamic spectral imaging (DSI) colposcopy has been developed to provide an objective element to cervix examinations and has been proven to increase sensitivity of detecting CIN2 + . We aimed to assess the performance of the DSI color map and compared it to histological diagnoses of cervical biopsies in determining the CIN grade present. METHODS: Women were included in a consecutive, prospective manner at Randers Regional Hospital, Denmark. Women were eligible to participate if they were referred for colposcopy due to abnormal cervical smear (threshold: ≥ ASCUS) or follow-up after previously diagnosed CIN. All women had four biopsies taken, one directed by colposcopists alone prior to viewing the DSI color map, one directed by the worst color on the respective DSI color map, and two additional biopsies. All biopsies were analyzed separately. We calculated sensitivity, specificity, positive predictive values, and negative predictive values (NPVs) with 95% confidence intervals (CIs). RESULTS: A total of 800 women were recruited. Of these, 529 (66.1%) were eligible for inclusion. The sensitivity of the DSI color map was found to be 48.1% (95% CI 41.1-55.1) in finding CIN grade 2 or worse (CIN2 +) when compared to the histological diagnosis of the DSI directed biopsy. This was 42.5% (95% CI 36.7-48.5) when compared to the final histological diagnosis of all four cervical biopsies and with an NPV of 53.5% (95% CI 50.5-56.5). CONCLUSION: The worst color indicated by the DSI map might not consistently reflect the true grade of cervical dysplasia present. Thus, even though the DSI color map indicates low-grade changes, colposcopists should still consider taking biopsies from the area as high-grade changes might be present. TRIAL REGISTRATION: NCT04249856, January 31 2020 (retrospectively registered).

Dynamic Spectral Imaging Colposcopy Versus Regular Colposcopy in Women Referred With High-Grade Cytology: A Nonrandomized Prospective Study.

OBJECTIVE: The aim of the study was to evaluate the sensitivity of dynamic spectral imaging (DSI) colposcopy compared with regular colposcopy for women referred with high-grade cervical cytology. METHODS: In a prospective, nonrandomized, multicenter study, we included women referred for colposcopy at hospital gynecology clinics with high-grade cytology. Women were examined using either a regular or DSI colposcope. In both groups, colposcopists located 1 area viewed as most suspicious. In the DSI group, this was done before viewing the DSI map. Subsequently, an area was chosen based on the worst color of the DSI map, and further additional biopsies were taken. All women had 4 cervical biopsies taken, all analyzed separately. The main outcome was sensitivity to find cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS: A total of 261 women were examined using DSI colposcopy, and 156 women were examined using regular colposcopy. The sensitivity for finding CIN2+ when using the DSI technology as an adjunctive technology was found to be 82.2% (95% CI = 75.9-87.4), based on an average of 1.4 biopsies. This was corresponding in sensitivity to 2 biopsies taken using regular colposcopy (80.3%; 95% CI = 72.3-86.8). There was no difference in sensitivity for CIN+ between the groups when 3 or more biopsies were taken. CONCLUSIONS: We found that the DSI colposcope may help direct biopsy placement; however, the improvement is based on small differences in needed biopsies and the clinical significance of this may be small. Multiple biopsies were still superior.

Accuracy of colposcopy-directed biopsy vs dynamic spectral imaging directed biopsy in correctly identifying the grade of cervical dysplasia in women undergoing conization: A methodological study.

INTRODUCTION: Dynamic spectral imaging (DSI) colposcopy has previously been found to improve sensitivity of CIN2+ detection. The aim of this study was to compare the histological diagnosis of colposcopic-directed biopsies (CDB) with that of DSI-directed biopsies in women undergoing conization, using the histological diagnosis of the conization specimen as gold standard. MATERIAL AND METHODS: Women referred for colposcopy were included in a prospective cohort study at Randers Regional Hospital, Denmark, from January 2016 to February 2019. All women had four cervical punch biopsies taken. The first biopsy was taken from the area that appeared most abnormal by conventional colposcopy (ie, CDB) and the second biopsy from the area that appeared most abnormal using the DSI map. An additional two biopsies were taken either from other visible lesions or as random biopsies. Biopsies were analyzed separately. If any biopsies revealed cervical dysplasia of such a degree that excisional treatment was recommended, the patient was referred for conization. Subsequently, we compared the histological diagnosis of CDB and DSI-directed biopsies with that of the cone biopsy. RESULTS: A total of 573 women were enrolled, 170 of which underwent conization. In women with an adequate colposcopy and representative biopsies (n = 124) there was an overall agreement rate between the worst biopsy diagnosis (of any four) and the conization diagnosis in 95.2% (95% CI 89.8-98.2) of women. CDB diagnosis agreed with the cone diagnosis in 80.6% (95% CI 72.6-87.2) of women. DSI-directed biopsy agreed with the cone diagnosis in 83.9% (95% CI 76.2-89.9) of women. The difference in detection rate between the CDB and the DSI-directed biopsy was, however, not significant (P = .54). Taking four biopsies increases the detection rate of cervical dysplasia to 95.2%, which was a significant increase from both CDB alone (P = .0008) and DSI-directed biopsy alone (P = .0053). CONCLUSIONS: We found no significant difference in the ability to identify the cervical dysplasia grade between CDB and DSI-directed biopsies. A higher detection rate of cervical dysplasia was achieved with four biopsies than with one CDB biopsy or one DSI-directed biopsy.

An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG).

INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods. MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot. RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method. CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

[Complete remission after Rituximab treatment in refractory hairy cell leukemia]. / Komplet remission efter rituximabbehandling ved refraktaer hårcelleleukaemi.

A 40 year-old man with hairy cell leukemia (HCL) was treated with Cladribin, but achieved only partial response (PR). As expected, both 2 and 5 years later the disease had progressed and the patient was therefore twice retreated with Cladribin. A bone marrow examination after the last Cladribin course showed complete response with residual disease (CR-RD). The patient received consolidation therapy with Rituximab, achieved complete response (CR) and was still in CR 9 months later. Rituximab is a good treatment option for patients with refractory HCL because of its significant activity and minimal toxicity.

Effects of pentoxifylline on the vascular response to injury after angioplasty in rabbit iliac arteries.

Pentoxifylline (PTX) inhibits the effects of several cytokines and reduces injury-related collagen accumulation. The aim of the present study was to investigate the effect of PTX on the vascular response to injury. We treated rabbits with PTX (100 mg/kg/day) or placebo (saline) subcutaneously from 2 days before angioplasty of an iliac artery until euthanasia 7 or 28 days later. At 7 days after injury, PTX treatment was associated with a more differentiated (less proliferation, more smoothelin-positive) intimal smooth muscle cell phenotype. Furthermore, PTX reduced myofibroblast accumulation in adventitia. At 28 days after injury, PTX-treated rabbits had a 48.5% larger lumen area (P = 0.03) and a 28.1% larger area within the external elastic lamina (P = 0.04). There were no significant differences between PTX-treated rabbits and the placebo group with regard to neointima and media area. Angioplasty induced marked neoadventitial hyperplasia, which was reduced by 20.5% (P = 0.01) in the PTX-treated group. Finally, PTX reduced collagen density in all three arterial layers. We conclude that PTX treatment induces less proliferation within the vessel wall early after angioplasty and increases late lumen size after angioplasty by a positive effect on vascular remodeling.

Catheter-based 32P beta-radiation after stent implantation in porcine coronary arteries: role of source-centering and geographical miss.

The present study examined the role of source-centering and geographical miss in vascular brachytherapy. After implantation of 13 mm long stents, 38 coronary arteries in 13 pigs were randomly assigned to centered brachytherapy (n = 13), eccentric brachytherapy (n = 13), or no radiation (n = 12). Geographical miss was avoided by careful placement of a 27 mm (32)P beta-radiation source. Restenosis was quantified by angiography, histomorphometry, and intravascular ultrasound at 28 days. Source-centering led to a significant (P < 0.001) reduction of in-stent area stenosis (centered radiation, 12% +/- 5%; eccentric radiation, 37% +/- 21%; control arteries, 41% +/- 13%). Despite 7 mm coverage of the edge segments, radiation was found to induce edge stenosis due to neointima formation and constrictive vascular remodeling. We conclude that centered radiation was superior to eccentric radiation in reducing in-stent luminal narrowing while radiation-induced edge stenosis was still observed despite extension of the radiation zone to 7 mm beyond the stent edges.

Adventitial myofibroblasts play no major role in neointima formation after angioplasty.

OBJECTIVE: Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts. DESIGN: Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for alpha-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype). RESULTS: Adventitial cells became transiently actin-positive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82 +/- 10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen. CONCLUSION: At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.