Prevalence of oral HPV infection in cervical HPV positive women and their sexual partners.

PURPOSE: Human papillomavirus (HPV) infection represents the primary cause of anogenital premalignant and malignant disease. Regarding the high prevalence of cervical HPV infection and the increasing incidence of HPV associated oropharyngeal cancer in recent years, a significant viral transmission from the cervical to the oral site, possibly depending on the sexual behavior must be considered. The present study aims to determine the prevalence of oral HPV infection in cervical HPV positive and negative women and their sexual partners. METHODS: Cervical HPV positive and negative women and their sexual partners took part in the study. Cervical smears, oral smears and mouthwashes were taken from women attending gynecological outpatient clinics in two different institutions. Further, oral smears as well as mouthwashes of their sexual partners were obtained whenever possible. HPV genotyping was performed using the Cobas® polymerase chain reaction and nucleic acid hybridization assay for the detection of 14 high-risk HPV types. In addition, all participants were invited to complete a personal questionnaire. RESULTS: 144 HPV positive and 77 HPV negative women and altogether 157 sexual partners took part in the study. Age, sexual behaviour, medication, smoking and alcohol consumption were distributed equally in both groups. Cervical HPV positive women had a significantly higher number of sexual partners. One woman with a HPV positive cervical smear and one partner of a woman with a HPV positive cervical smear showed an oral HPV infection. No oral HPV infections were detected in the HPV negative control group. The overall incidence of oral HPV infection was 0.5%, the incidence of oral HPV infection in women with a positive cervical smear was 0.7%. CONCLUSION: The data demonstrate that the overall risk of an oral HPV infection is low. HPV transmission to the oropharynx by autoinoculation or oral-genital contact constitute a rare and unlikely event.

3D optical coherence tomography of cervical intraepithelial neoplasia--early experience and some pitfalls.

OBJECTIVES: To compare two different systems for optical coherence tomography for the diagnosis of cervical dysplasia and to assess potential benefits of three-dimensional imaging. MATERIALS AND METHODS: OCT images were taken from unsuspicious and suspicious areas of fresh conisation specimens using two different imaging systems, one with the capability to produce three-dimensional images. All OCT images were separately evaluated by two blinded investigators based on a 6-grade classification (normal, inflammation, CIN 1, CIN 2, CIN 3, squamous carcinoma) and later compared to the corresponding histology. Sensitivity and specificity of OCT in detecting cervical dysplasia were determined. RESULTS: OCT images using both OCT systems were taken from 46 sites in ten conisation specimens and later compared to the corresponding histology. CIN lesions were diagnosed correctly by the two-dimensional OCT system with a sensitivity and specificity of 91% and 78% accordingly. Using the three-dimensional system sensitivity and specificity were 82% and 86% accordingly. CONCLUSIONS: Both OCT systems used were highly sensitive in identifying cervical intraepithelial neoplasia. Despite technical problems experienced in the present series, we believe that three-dimensional imaging has the potential to further improve the accuracy of optical coherence tomography.

The surgical treatment of Graves' disease in children and adolescents.

BACKGROUND: Surgery as definitive treatment of pediatric Graves' disease is recommended for children and adolescents experiencing adverse effects of thionamides or disease relapse after at least 2 years of medical treatment. In addition, it is indicated in patients with a large goiter or with suspicious nodules. Total or near-total thyroidectomy should be performed, since subtotal thyroidectomy is associated with a high risk of relapse in this group. Patients should be referred to surgeons experienced in thyroid surgery because studies show that children and adolescents have a higher complication rate than adults. METHODS: This is a retrospective matched case-control study. To analyze postoperative morbidity of children and adolescents (mean age = 15 ± 3 years) with Graves' disease who underwent total thyroidectomy between 2000 and 2010 in our department, a statistically identical group of adults (mean age = 46 ± 3) who also underwent total thyroidectomy for Graves' disease was matched as a control. End points were surgical complications like postoperative bleeding, transient and permanent recurrent laryngeal nerve palsy, and transient and permanent hypoparathyroidism. RESULTS: There was no significant difference in the mean operation time (137 ± 33 min), the rate of intraoperative parathyroid gland autotransplantation (9.5%), postoperative bleeding (4.8%), transient and permanent recurrent laryngeal nerve palsy (4.8 and 0%), and transient and permanent hypocalcemia (28.6 and 0%). CONCLUSION: Total thyroidectomy in children and adolescents with Graves' disease performed in a department that specializes in endocrine surgery is a safe procedure with no higher complication rates than total thyroidectomy in adults with Graves' disease.

Optical coherence tomography as a non-invasive imaging technique for preinvasive and invasive neoplasia of the uterine cervix.

OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features of tissue up to 2 mm in depth in real time. The purpose of this study was to evaluate the feasibility of OCT for the identification of precancerous (cervical intraepithelial neoplasia (CIN)) and cancerous lesions of the uterine cervix. METHODS: We conducted a prospective study on the use of OCT in women with suspected CIN. OCT images were obtained on colposcopy from non-suspicious and suspicious areas, and were evaluated independently by two investigators and later compared with the corresponding histology. The sensitivity, specificity, negative and positive predictive values and accuracy of the new technique in identifying CIN or carcinoma were calculated. RESULTS: Of a total of 610 OCT images, 97 from suspicious areas in 60 women were compared with the corresponding histology. Sixty-three of 67 CIN lesions and four invasive carcinomas were diagnosed correctly on evaluation of the OCT images by the first observer. There were 69 true-positive, 11 true-negative, 13 false-positive and four false-negative results, giving a sensitivity of 95% and a specificity of 46%. CONCLUSION: OCT is a rapid, easy-to-use modality that provides real-time, microarchitectural information of the cervical epithelium. Further refinement of this technology will lead to OCT systems with a significantly higher resolution and may result in better differentiation of cancerous and precancerous lesions.

Validity and limits of intraoperative parathyroid hormone monitoring during minimally invasive parathyroidectomy: a 10-year experience.

BACKGROUND: The availability of intraoperative intact parathyroid hormone monitoring allows the success of minimally invasive parathyroidectomy to be ensured during the operation. However, false-negative results leading to unnecessary explorations and difficulties in interpreting the data raise concern about the effectiveness of the method. METHODS: Patients with primary hyperparathyroidism (pHPT) and one unequivocally enlarged parathyroid gland on preoperative ultrasound or (99m)Tc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy according to the technique initially described by Miccoli. Intraoperatively, rapid electrochemiluminescence immunoassay was used to measure intact parathyroid hormone (iPTH) levels before the operation, after complete mobilization of the adenoma (preexcision value), and 5, 10, and 15 min after the excision. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels and subsequent attainment of the normal range within 15 min were observed. RESULTS: Between November 1999 and November 2009, 235 (43%) of 546 patients with pHPT were eligible for a minimally invasive approach. Intraoperative iPTH monitoring showed 221 true-positive, 1 false-positive, 6 false-negative, and 7 true-negative results. This calculated to a sensitivity of 97% and a specificity of 88%. CONCLUSIONS: Despite the availability of high-resolution ultrasound and (99m)Tc-SestaMIBI scintigraphy, the presence of multiple glandular disease cannot be ruled out completely. Although the authors observed six false-negative results, they believe that intraoperative iPTH monitoring represents a valuable asset for minimally invasive parathyroidectomy because it identifies sporadic hyperplasia.

The significance of HPV in the follow-up period after treatment for CIN.

PURPOSE OF INVESTIGATION: High-risk anogenital human papillomavirus (HPV) infections are causally related to cervical cancer. Successful treatment of cervical intraepithelial neoplasia (CIN) results in complete eradication of HPV in most cases. There is an increasing interest regarding the role of HPV testing in the follow-up period after treatment for CIN. PATIENTS AND METHODS: This retrospective study includes 107 women who underwent conization for histologically verified CIN. All of them had HPV testing pre- and postoperatively. HPV testing was carried out using a hybrid capture assay (HC2). The mean follow-up period was 21.4 months (range 2-76 months). The data were analyzed with respect to success of conization, HPV persistence/recurrence and CIN recurrence. Sensitivity, specificity and negative predictive value (NPV) of HPV testing were assessed and compared to the cytological results. RESULTS: Preoperatively, 97 of 107 women were HPV positive. Ninety-seven conizations showed negative resection margins with 86 women becoming HPV negative. In the following months, nine of these HPV negative women became HPV positive again. Out of ten conizations with positive resection margins, six women became HPV negative. Recurrent CIN 2/3 lesions were observed in 11 women, nine of whom had persistent positive HPV testing throughout the entire study period. Regarding CIN recurrence HPV testing showed a sensitivity of 93%, a specificity of 85% and a NPV of 99%. CONCLUSIONS: The sensitivity of HPV testing concerning persistent or recurrent CIN as well as the NPV are high. The present data suggest that HPV testing should be integrated in a follow-up algorithm after treatment for CIN by conization.

[Optical coherence tomography: preliminary results with a new noninvasive technique for evaluating uterine cervical tissue and vulvar epithelium]. / La tomografia a coerenza ottica, una nuova tecnica non invasiva per valutare il tessuto cervicale uterino e l'epitelio vulvare. Risultati preliminari.

AIM: Optical coherence tomography (OCT) is a noninvasive diagnostic imaging technique that captures high-definition real-time images at near-microscopic resolution (1-2 mm below the surface) of biological tissue morphology. The aim of this study was to define the characteristics of uterine cervical and vulvar pathologies by means of OCT and to compare OCT findings versus histopathological features. MATERIALS AND METHODS: This prospective single-center study was approved by the regional ethical committee. The OCT scans were performed in women with suspected cervical intraepithelial neoplasia (CIN) or vulvar intraepithelial neoplasia (VIN). The suspicious lesions were identified using colposcopy, visualized by OCT, and then biopsied. The OCT scans were evaluated by two independent examiners. The results were then compared with the histopathological findings. The sensitivity and specificity of OCT were calculated. RESULTS: Overall, 50 of the 54 CIN and 2 carcinomas confirmed on histology were correctly diagnosed with OCT, yielding a sensitivity of 93%; specificity was 33%, with 8 false positives and 4 true negatives. In 10 patients with suspected VIN, 19 OCT images were compared with the corresponding biopsies. Three states of tissue structure could be distinguished, with typical features of normal tissue and tissue altered by neoplastic transformation. CONCLUSION: OCT is a noninvasive, fast and simple technique to obtain real-time information on tissue microstructure. Further study is needed to assess its use in routine diagnostic imaging; however, these preliminary results indicate its high sensitivity.

[Optical coherence tomography for differentiation of parathyroid gland tissue]. / Optische Kohärenztomographie als Verfahren zur Differenzierung von Nebenschilddrüsengewebe.

BACKGROUND: Optical coherence tomography (OCT) is a high-resolution imaging technique that allows the identification of microarchitectural features in real-time. OBJECTIVE: Can OCT be used to differentiate parathyroid tissue from other cervical tissue entities? MATERIAL AND METHODS: All investigations were carried out during cervical operations. Initially, ex vivo images were analyzed to define morphological imaging criteria for each tissue entity. These criteria were used to evaluate a first series of ex vivo images. In a second phase the practicability of the technique was investigated in vivo and in the third phase backscattering intensity measurements were analyzed employing linear discriminant analysis (LDA). RESULTS: In the ex vivo series parathyroid tissue could be differentiated from other tissue entities with a sensitivity and specificity of 84  % and 94  %, respectively. Parathyroid tissue was correctly identified in the in vivo series in only 69.2 %. The analysis of backscattering intensity profiles employing LDA reliably distinguished between the different tissue types. CONCLUSION: The OCT images displayed typical characteristics for each tissue entity. Due to technical problems in handling the probe the in vivo OCT images were of much poorer quality. Backscattering intensity measurements illustrated that OCT images provide an individual profile for each tissue entity independent of the defined morphological assessment criteria. The results show that OCT is fundamentally suitable for intraoperative differentiation of tissues.

HPV Vaccination: Attitude and Knowledge among German Gynecologists.

Purpose: In order to achieve a higher vaccination rate, education on HPV as well as options for prophylaxis performed by doctors is of great importance. One opportunity to increase the protection against HPV would be vaccinating boys. This study evaluated attitude and knowledge among German gynecologists regarding HPV vaccination, especially in boys. Material and Methods: A questionnaire with 42 questions about demographics, attitude and knowledge about HPV and HPV vaccination was sent to members of the German Society for Gynecology and Obstetrics (DGGG). Results: 998 out of 6567 addressed gynecologists participated. Knowledge about HPV, associated diseases and possible HPV vaccines was high among participants. The attitude towards vaccination in boys as well as girls was positive. Only 8.2 % refused to vaccinate their sons whereas 2.2 % refused to do this for their daughters. However, only few gynecologists vaccinated their daughters and sons against HPV. Main reason for girls was an age outside of vaccination guidelines; for boys it was the lack of cost coverage. Conclusion: The willingness of gynecologists to perform HPV vaccination in boys is as high as for girls. However, sons of gynecologists are only rarely vaccinated against HPV. Main reason is the lack of cost coverage. Vaccinating boys could decrease the disease burden in males, as well as protect women by interrupting ways of transmission. Since the main argument against vaccination of boys is only of financial nature, the necessity of a vaccination recommendation for boys needs to be re-evaluated taking into account the cost-reduced 2-dose vaccination scheme.

Minimally invasive video-assisted parathyroidectomy.

BACKGROUND: The standard surgical procedure for parathyroidectomy consists of bilateral cervical exploration and the visualization of all four parathyroid glands. However, improved preoperative localization techniques and the availability of intraoperative intact parathyroid hormone (iPTH) monitoring now allow single adenomas to be treated with minimally invasive techniques. METHODS: Patients with primary hyperthyroidism (pHPT), who were found to have one unequivocally enlarged parathyroid gland on preoperative ultrasound and 99mTc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy by an anterior approach. Intraoperatively, rapid electrochemiluminescense immunoassay was used to measure iPTH levels shortly before and 5, 10, and 15 mins after excision of the adenoma. The operation was considered successful when a >50% decrease in preexcision iPTH levels was observed after 5 min. RESULTS: Between November 1999 and May 2000, 10 of 22 patients with pHPT were deemed eligible for the minimally invasive approach. In all cases, the adenoma was removed successfully. However, in two cases, intraoperative iPTH monitoring did not show a sufficient decrease in iPTH values. Subsequent cervical exploration revealed a double adenoma in one case and hyperplasia in the other. CONCLUSIONS: Even when high-resolution ultrasound and 99mTc-SestaMIBI scintigraphy are used, the presence of multiple glandular desease cannot be ruled out entirely. When the minimally invasive approach is contemplated, intraoperative iPTH monitoring is indispensible to ensure operative success. However, in selected cases, minimally invasive parathyroidectomy represents an excellent alternative to the conventional technique.

Minimally invasive video-assisted parathyroidectomy and intraoperative parathyroid hormone monitoring. The first 36 cases and some pitfalls.

BACKGROUND: The success of parathyroid surgery depends on the identification and removal of all hyperactive parathyroid tissue. At this writing, bilateral cervical exploration and identification of all parathyroid glands represent the operative standard for primary hyperparathyroidism (pHPT). However, improved preoperative localization techniques and the availability of intraoperative parathyroid hormone monitoring prepare the way for minimally invasive procedures. METHODS: Patients with pHPT and one unequivocally enlarged parathyroid gland on preoperative ultrasound and 99mTc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy by an anterior approach. Intraoperatively, a rapid chemiluminescense immunoassay was used to measure intact parathyroid hormone (iPTH) levels shortly before and then 5, 10, and 15 min after excision of the adenoma. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels was observed after 5 min. RESULTS: Between October 1999 and November 2001, 36 of 82 patients with pHPT were eligible for a minimally invasive approach. A conversion to open surgery became necessary in five patients because of technical problems. In three cases, intraoperative iPTH monitoring showed no sufficient decrease in iPTH values. In these cases, subsequent cervical exploration showed one double adenoma and two hyperplasias, respectively. In two patients we had difficulty interpreting intraoperative iPTH values, resulting in persistent pHPT. CONCLUSIONS: Despite the use of high-resolution ultrasound and 99mTc-SestaMIBI scintigraphy, the presence of multiple glandular disease cannot be ruled out completely. Intraoperative iPTH monitoring to ensure operative success is indispensible for a minimally invasive approach. Despite our problems with iPTH monitoring in two patients, we believe that in selected cases, minimally invasive parathyroidectomy represents an attractive alternative to conventional surgery.

Retinoid X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) expression in breast cancer: an immunohistochemical study.

BACKGROUND/AIM: The role of retinoid X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) in breast cancer has been well studied in vitro. The aim of the study was to assess the presence of these molecules in human breast cancer specimens and correlate them with major clinicopathological features. PATIENTS AND METHODS: Tissue sections from 82 breast cancer cases clustered according to histological grade, lymph node (LN) and hormone receptor (HR) status were assessed by immunohistochemistry for RXRα and PPARγ. RESULTS: RXRα was found to be strongly and moderately expressed in 11 (14.10%) and 33 (42.31%) cases, respectively. PPARγ was found to be strongly and moderately expressed in 33 (41.25%) and 25 (31.25%) cases, respectively. Only RXRα expression was inversely correlated with histological grade. Surprisingly, significantly elevated PPARγ expression was found in cases with positive LN status. Survival analysis did not yield significant results. CONCLUSION: Our data support the current thesis of RXRα being a potential target for feature molecular interventions.

[Thrombotic thrombocytopenic purpura--a rare and difficult differential diagnosis to HELLP syndrome in late pregnancy]. / Die thrombotisch thrombozytopenische Purpura--Eine seltene und schwierige Differenzialdiagnose zum HELLP-Syndrom in der Spätschwangerschaft.

Thrombotic thrombocytopenic purpura (TTP) represents a rare complication mainly in the second trimester and can, in its early stage, mimic HELLP syndrome. At 38 weeks of gestation, a 40-year-old primigravida with elevated blood pressure, thrombocytopenia and elevated liver enzymes was diagnosed with HELLP syndrome. Despite a Ceasarean section her laboratory parameters remained pathological with severe thrombocytopenia and hemolysis. In addition, the patient developed neurological comatose-like symptoms. The diagnosis of TTP was made after further tests revealed fragmented red cells in the blood, autoantibodies against ADAMTS13 and a nearly total loss of ADAMST13 plasma activity. The patient fully recovered following repeated plasmapheresis and plasma substitution as well as systemic treatment with dexamethasone. If laboratory parameters do not normalise promptly in spite of the correct treatment for an assumed HELLP syndrome, TTP may be the underlying pathology. As rapid assays for antibodies against ADAMTS13 are not available yet, special consideration must be given to the clinical details in order to make a correct diagnosis.

[Intraoperative monitoring of intact parathyroid hormone during surgery for primary hyperparathyroidism]. / Intraoperative Bestimmung des intakten Parathormons (iPTH) in der Chirurgie des primären Hyperparathyreoidismus.

The aim of the present study was to evaluate a new immunometric assay for intraoperative parathyroid hormone monitoring. The test was applied in 70 patients who underwent surgery for primary hyperthyroidism (pHPT) between 6/1999 and 6/2001. Among these patients, 61 showed a solitary adenoma, eight a hyperplasia and one a double adenoma. Intraoperative iPTH samples were taken at the beginning of the operation and 5, 10 and 15 min after removal of the parathyroid gland. Criterion for a successful operation were a decrease of iPTH levels of more than 50 % within 5 min and of more than 60 % within 15 min after parathyroidectomy. Following the removal of a solitary adenoma, iPTH levels decreased by 63 % (+/- 13 %) after 5 min and by 76 % (+/- 10 %) after 15 min respectively. In case of hyperplasia, a significant decrease of iPTH levels was not observed until a subtotal parathyroidectomy had been carried out. In the present study there were 2 false negative and one false positive results corresponding with a sensitivity of 97 % and a specificity of 89 % for prediction of a solitary adenoma. In our opinion, intraoperative iPTH monitoring using this new assay allows the safe distinction between adenoma and multiglandular disease. It represents a valuable adjunct to surgical skill as it permits minimally invasive operations for solitary adenomas, and in case of recurrent surgery helps to detect the region of interest by selective venous sampling for parathyroid hormone.