Philipp Soergel

Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate

CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non‐invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection.

Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia

OBJECTIVE Photodynamic therapy has the potential of a minimal invasive outpatient procedure for CIN patients at reproductive ages. The purpose of this study was to examine the pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate (HAL) in patients with cervical intraepithelial neoplasia (CIN). STUDY DESIGN Twenty-four women with CIN 1-3 received 4 mmol/L or 10 mmol/L HAL dissolved in thermolabile pluronic F 127 gel topically 5-720 minutes before surgical conization. The microscopic fluorescence pattern was quantified by ex vivo fluorescence spectroscopy at a wavelength of 635 nm and semiquantitatively by digital image analysis from cryosections. RESULTS With 4 and 10 mmol/L HAL, porphyrin fluorescence intensity increased over time, reaching a peak after 180-540 minutes application intervals in CIN and normal epithelium. However, the peak was much more pronounced in CIN than in normal tissues. The fluorescence intensity with 10 mmol/L was significantly higher than that with 4 mmol/L in CIN tissues (P < .05). Maximum intensity could generally be detected in the lower layer of the epithelium. CONCLUSION HAL seems to be a promising molecule for fluorescence diagnosis. For further treatment studies, we recommend application of 10 mmol/L HAL 300-540 minutes before photodynamic therapy in CIN.

Diagnostic performance and inter-observer concordance in lesion detection with the automated breast volume scanner (ABVS)

BackgroundAutomated whole breast ultrasound scanners of the latest generation have reached a level of comfortable application and high quality volume acquisition. Nevertheless, there is a lack of data concerning this technology. We investigated the diagnostic performance and inter-observer concordance of the Automated Breast Volume Scanner (ABVS) ACUSON S2000™ and questioned its implications in breast cancer diagnostics.MethodsWe collected 100 volume data sets and created a database containing 52 scans with no detectable lesions in conventional ultrasound (BI-RADS®-US 1), 30 scans with benign lesions (BI-RADS®-US 2) and 18 scans with breast cancer (BI-RADS®-US 5).Two independent examiners evaluated the ABVS data on a separate workstation without any prior knowledge of the patients’ histories.ResultsThe inter-rater reliability reached fair agreement (κ=0.36; 95% confidence interval (CI): 0.19-0.53). With respect to the true category, the conditional inter-rater validity coefficient was κ=0.18 (95% CI: 0.00-0.26) for the benign cases and κ=0.80 (95% CI: 0.61-1.00) for the malignant cases.Combining the assessments of examiner 1 and examiner 2, the diagnostic accuracy (AC), sensitivity (SE) and specificity (SP) for the experimental ABVS were AC = 79.0% (95% CI: 67.3-86.1), SE = 83.3% (95% CI: 57.7-95.6) and SP = 78.1% (% CI: 67.3-86.1), respectively.However, after the ABVS examination, there were a high number of requests for second-look ultrasounds in up to 48.8% of the healthy women due to assumed suspicious findings in the volume data.In an exploratory analysis, we estimated that an ABVS examination in addition to mammography alone could detect a relevant number of previously occult breast cancers (about 1 cancer in 300 screened and otherwise healthy women).ConclusionsThe ABVS is a reliable imaging method for the evaluation of the breast with high sensitivity and a fair inter-observer concordance. However, we have to overcome the problem of the high number of false-positive results. Therefore, further prospective studies in larger collectives are necessary to define standard procedures in image acquisition and interpretation. Nevertheless, we consider the ABVS as being suitable for integration into breast diagnostics as a beneficial and reliable imaging method.

Ultrasound real-time elastography can predict malignancy in BI-RADS®-US 3 lesions

BackgroundLesions of the breast that are classified BI-RADS®-US 3 by ultrasound are probably benign and observation is recommended, although malignancy may occasionally occur.In our study, we focus exclusively on BI-RADS®-US 3 lesions and hypothesize that sonoelastography as an adjunct to conventional ultrasound can identify a high-risk-group and a low-risk-group within these patients.MethodsA group of 177 breast lesions that were classified BI-RADS®-US 3 were additionally examined with real-time sonoelastography. Elastograms were evaluated according to the Tsukuba Elasticity Score. Pretest and posttest probability of disease (POD), sensitivity (SE), specificity (SP), positive (PPV) and negative predictive values (NPV) and likelihood-ratios (LR) were calculated. Furthermore, we analyzed the false-negative and false-positive cases and performed a model calculation to determine how elastography could affect the proceedings in population screening.ResultsIn our collection of BI-RADS®-US 3 cases there were 169 benign and eight malignant lesions. The pretest POD was 4.5% (95% confidence interval (CI): 2.1–9.0). In patients with a suspicious elastogram (high-risk group), the posttest POD was significantly higher (13.2%, p = 0.041) and the positive LR was 3.2 (95% CI: 1.7–5.9). With a benign elastogram (low-risk group), the posttest POD decreased to 2.2%. SE, SP, PPV and NPV for sonoelastography in BI-RADS®-US 3 lesions were 62.5% (95% CI: 25.9–89.8), 80.5% (95% CI: 73.5–86.0), 13.2% (95% CI: 5.0–28.9) and 97.8% (95% CI: 93.3–99.4), respectively.ConclusionsSonoelastography yields additional diagnostic information in the evaluation of BI-RADS®-US 3 lesions of the breast. The examiner can identify a low-risk group that can be vigilantly observed and a high-risk group that should receive immediate biopsy due to an elevated breast cancer risk.

Photodynamic therapy of cervical intraepithelial neoplasia 1–3 and human papilloma virus (HPV) infection with methylaminolevulinate and hexaminolevulinate—A double-blind, dose-finding study†

Cervical intraepithelial neoplasia (CIN) 1–3 is the precursor of invasive cervical cancer and associated with human papillomavirus infection. Standard treatment is surgical and may be associated with subsequent pregnancy complications. Photodynamic therapy (PDT) of CIN may be an interesting alternative.

Photodynamic therapy for intraepithelial neoplasia of the lower genital tract

Photodynamic Diagnosis (PDD) and Therapy (PDT) are modern methods which are evaluated in different fields in gynaecology. PDT has been successfully evaluated in human papillomavirus-related (HPV) genital dysplasia like CIN and VIN. The aim of this review is to give an overview about current applications.

Effects of photodynamic therapy using topical applied hexylaminolevulinate and methylaminolevulinate upon the integrity of cervical epithelium

Cervical intraepithelial neoplasia (CIN) is associated with genital human papillomavirus (HPV) infection and represents the precursor of cervical cancer. Established ablative treatment methods may cause substantial complications in following pregnancies including premature delivery and the birth of low‐weight babies. Photodynamic therapy (PDT) of CIN using esters of 5‐aminolevulinic acid (5‐ALA) represents a promising alternative. However, it has not been analyzed yet if the PDT itself leads to sustained damage of the cervical tissue. This study aims at evaluating the effect of hexylaminolevulinate (HAL) and methylaminolevulinate (MAL) PDT on cervical tissue.

RETRACTED: Reconstructive, organ-preserving microsurgery in tubal infertility: still an alternative to in vitro fertilization

In this retrospective study, we observed a total of 553 patients with tubal infertility who underwent microsurgical reconstructive surgery of the fallopian tubes (including adhesiolysis, anastomosis, fimbrioplasty, salpingostomy, and refertilization after former sterilization). The pregnancy (43.4%) and birth (29.2%) rates after microsurgery for acquired tubal damages (abortion: 6.4%; ectopic pregnancy: 7.9%) were higher than after single in vitro fertilization (28.4% and <20%, respectively; data from German IVF register). The pregnancy (73%) and birth (50.6%) rates after the reversal of sterilization also were higher (abortion: 15.7%; ectopic pregnancy: 6.7%). The advantages of reconstructive microsurgery over in vitro fertilization include the ideally permanent restoration of a womans ability to conceive naturally in every cycle that she ovulates, a high postoperative birth rate overall, and avoidance of multiple births.

Aromatase Inhibitors as Solely Treatment in Postmenopausal Breast Cancer Patients

Abstract:  Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty‐six patients with fifty‐seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high‐end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52–102 years). All patients suffered from breast cancer. The mean follow‐up interval was 40 months (range 5–92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.

The cost efficiency of HPV vaccines is significantly underestimated due to omission of conisation-associated prematurity with neonatal mortality and morbidity

Introduction: Cervical intraepithelial neoplasia (CIN) represents the precursor of invasive cervical cancer and is associated with human papillomavirus infection (HPV) against which two vaccines have been approved in the last years. Standard treatments of high-grade CIN are conisation procedures, which are associated with an increased risk of subsequent pregnancy complications like premature delivery and possible subsequent life-long disability. HPV vaccination has therefore the potential to decrease neonatal morbidity and mortality. This has not been taken into account in published cost-effectiveness models. Material and Methods: We calculated the possible reduction rate of conisations for different vaccination strategies for Germany. Using this rate, we computed the reduction of conisation-associated preterm deliveries, life-long disability and neonatal death due to prematurity. The number of life-years saved (LYS) and gain in quality-adjusted life-years (QALYs) was estimated. The incremental costs per LYS / additional QALY were calculated. Results: The reduction of conisation procedures was highest in scenario I (vaccination coverage 90% prior to HPV exposition) with about 50%. The costs per LYS or additional QALY were lowest in scenario I, II and III with 45,101 € or 43,505–47,855 € and rose up to 60,544 € or 58,401–64,240 € in scenario V (50% vaccinated prior to sexual activity + additional 20% catch-up at a mean age of 20 y). Conclusion: Regarding the HPV 16 / 18 vaccines as “vaccines against conisation-related neonatal morbidity and mortality” alone, they already have the potential to be cost-effective. This effect adds up to reduction of cervical cancer cases and decreased costs of screening for CIN. Further studies on cost-effectiveness of HPV vaccination should take the significant amount of neonatal morbidity and mortality into account.