No abstract

The present study aimed to identify the factors that independently contribute to disease recurrence among women first-time treated for high-grade cervical intraepithelial neoplasia (CIN) during 4-6 years of follow-up. Overall, 529 of 530 eligible patients participated; these patients all attended a 1st follow-up appointment ~6 months post-conization, at which time high-risk human-papillomavirus (HPV) testing, liquid-based cytology and colposcopy were performed. Full data on margin excision status, other aspects of initial treatment and comorbidity were obtained. At least one subsequent follow-up was attended by 88% of patients. A total of 22 recurrent cases were detected during follow-up. Detected recurrence was the outcome of focus for multiple logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed. Four significant independent risk factors were identified: Age 45 years or above (OR=3.5, 95% CI=1.3-9.9), one or both unclear or uncertain margins (OR=5.3, 95% CI=2.0-14.2), positive HPV at 1st follow-up (OR=5.8, 95% CI=2.0-16.8), and abnormal cytology at 1st follow-up (OR=3.9, 95% CI=1.4-11.0). Bivariate analysis revealed that persistent HPV positivity was associated with recurrence (P<0.01). These findings indicated that incomplete excision of the CIN lesion may warrant more intensive subsequent screening, regardless of early post-conization HPV findings. Although early post-conization positive HPV was a powerful, independent predictor of recurrent high-grade CIN, over one-third of the patients with detected recurrence had a negative early post-conization HPV finding. These patients returned for routine screening, at which time, in most cases, HPV status was positive, thus indicating the need for repeated HPV evaluation. Especially during the on-going pandemic, home vaginal self-sampling is recommended. Particular attention is required for women aged ≥45 years. In addition, although not statistically significant, relevant comorbidities, especially autoimmune conditions, warrant consideration in clinical decision-making. Women who have been treated for high-grade CIN are at risk for recurrent disease and progression to cervical cancer; therefore, they require careful, individualized follow-up to avoid these adverse consequences.

The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.

Background The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling. Aims We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD. Methods Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism. Results Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s2, p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15–24] vs 11 [8–14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = − 0.39, p = 0.005). Conclusions Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.