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Background Since 2020, co-testing for women over the age of 35 has been a new strategy for cervical cancer screening in Germany. In this study, we investigated the added value of co-testing in organized cervical screening for the German screening population. Methods A total of 1956 women were referred to our large dysplasia consultation institution due to abnormal screening results in the first round of screening between 2020 and 2022. The endpoint of this retrospective study was the posttest probability of a CIN 2+/CIN 3 + lesion on the cervix uteri. In addition, the influence of HPV subtypes on the endpoints was investigated. Results CIN 2 + or CIN 3 + lesions were diagnosed in 21.6% and 13.0%, respectively, of the patients. The probability of severe dysplasia increases with the grade of cytological abnormality and is dependent on the HPV subtype. The probability for detecting invasive cervical cancer (16 patients in total) was significantly higher for women with HPV16 infection than for women with HPV infection of other high-risk types (odds ratio 11.18; 95% confidence interval 3.01, 40.81). CIN 2 + lesions were diagnosed in 10.1% of patients with normal cytology. Conclusions CIN 2 + lesions could be detected in more than every 5th woman with an abnormal screening result. The proportion of CIN 3 + patients was significantly higher in the presence of HPV 16.

Purpose To characterize the clinical presentation and outcome of patients with vaginal intraepithelial neoplasia (VAIN). Methods Medical records of 65 women with VAIN treated between 2005 and 2012 at the colposcopy clinic of a German university hospital were retrospectively evaluated for VAIN grade, HPV status, VAIN localization, treatment method and relapse rate. Follow-up data were available for 53 patients (82 %). Results Mean age was 61 years (range 32–89 years). Most lesions (55 %) were found in the upper vaginal third; 42 % were multifocal. Multifocal VAIN was more frequently HPV positive than single lesions ( p  = 0.059). Of all women with known HPV status, 83 % were high-risk (HR) HPV positive and 32 % had a simultaneous CIN earlier or at the same time as the VAIN, mostly CIN 3 (66 %). Two-thirds had a hysterectomy in the past, often because of high-grade CIN. Most cases of VAIN were treated with CO 2 laser vaporization. A relapse of the disease could be confirmed for 57 %. HR-HPV positive VAIN was significantly more likely to relapse than HR-HPV negative VAIN ( p  = 0.005). There were three cases of vaginal cancer with surrounding VAIN 3 or vaginal cancer diagnosed after primary treatment of VAIN 3 and one case of vaginal cancer during follow-up 22 months after the first laser vaporization. All of these cases were HR-HPV positive. Conclusions VAIN has a high relapse rate and a high progression rate to invasive cancer especially if HR-HPV positive. Therefore, adequate follow-up examinations are mandatory.

The concept of intraoperative in vivo diagnosis and selective resection of infiltrated lymph nodes in ovarian cancer has not been evaluated despite the increased morbidity associated with pelvic and paraaortic lymph node dissection and its questionable therapeutic value. Fluorescence photodetection is based on the application of a photosensitizer relatively selective for malignant tissue, which after light activation of appropriate wavelength, shows fluorescence. Six hours after oral application of 10 mg/kg body weight 5-aminolevulinic acid, the abdominal cavity of a patient with suspicion of recurrent ovarian cancer was inspected using a laparoscope and blue light at 380-440 nm. Spectral measurements at a wavelength of 635 nm, multiple peritoneal biopsies, and lymph node excisions were performed. White light inspection and porphyrin fluorescence photodetection revealed no intraperitoneal metastases and multiple biopsies were negative. Fluorescence-positive lymph nodes were visible only in the left common iliac region and a specific porphyrin fluorescence peak could be detected. In contrary, no increased porphyrin fluorescence of intraperitoneal tissues or skin was seen. Fluorescence microscopy showed the characteristic red fluorescence in the infiltrated parts of the lymph node tissue by the papillary ovarian cancer. Histology of the other sites was negative. No systemic or cutaneous side effects were recorded. This data is a proof of the concept that porphyrin fluorescence-guided lymph node metastasis detection is possible in ovarian cancer and should stimulate further research in this field.

We compared a dermoglandular rotation flap (DGR) in the upper inner, lower inner, and upper outer quadrant regarding similar aesthetic results, patient satisfaction, and comfort after breast-conserving therapy with standard segmentectomy (SE). Between 2003 and 2011, 69 patients were treated with breast-conserving surgery using DGR for cancers with high tumor-to-breast volume ratios or skin resection in the three above mentioned quadrants; 161 patients with tumors in the same quadrants were treated with SE. The outcome of the procedures was assessed at least 7 months after completed radiation therapy using a patient and breast surgeon questionnaire and the BCCT.core software. Symmetry, visibility of the scars, the position of the nipple-areola complex, and the appearance of the treated breast were each assessed on a scale from 1 to 4 by an expert panel and by the patients. Univariate and multivariate analysis were used to evaluate the relationship between patient-, tumor-, and treatment-dependent factors and patient satisfaction. 94.2% of the patients with rotation flaps and 83.5% of the patients with lumpectomy were very satisfied with the cosmetic appearance of their breast. Younger patient age was significantly associated with a lower degree of satisfaction. DGR provides good cosmetic results compared with SE and shows high patient satisfaction despite longer scarring and higher median resection volume.

The individual risk assessment of fetal Down's syndrome based on measurement of nuchal translucency (NT) according to Nicolaides, optionally complemented by the determination of PAPP-A and free beta HCG has progressively supplanted other search strategies for fetal aneuploidies. It could be shown that this diagnostic strategy equally detects other numeric aneuploidies at a comparable rate. A positive test result is also predictive for the presence of a fetal malformation. In this field, several computer programs are available for clinical use. The objective of our study was to re-evaluate the first consecutive 1463 NT-risk calculations determined by Nicolaides' method and to compare the risk calculation to the JOY software (NT-risk calculation module, JOY Patient Database) introduced in 2002. At the Department of Obstetrics and Gynecology, Hannover Medical School, 1463 consecutive complete data sets comprising first trimester screening performed between May 2, 2000 and June 26, 2003 and corresponding fetal outcome were analysed using risk assessment based on the Nicolaides method (PIA Fetal Database NT-Module) and compared with the risk evaluation as determined by the JOY software (JOY Patient Database NT module). A risk exceeding 1:300 was considered to indicate the need for further invasive testing. In a first step, only cytogenetically detectable chromosomal aberrations were analysed. Then, a second evaluation including fetal malformations was performed. Among the 1463 cases, 1445 (98.77%) fetuses revealed to be cytogenetically healthy. Both softwares showed identical detection rates at the genetic and somatic level:13 cases of Down-Syndrome (0.89%), 2 cases of trisomy 18 (0.14%), one case of triploidy, one Turner-Syndrome, one Klinefelter-Syndrome (0.07% each) were detected. A positive test result was found in 15 cases ending in a spontaneous abortion, intrauterine death or peripartum death (1.03%) and in 22 cases of fetal malformation (1.50%). At the level of genetic detection the test positive rate dropped from 92 (PIA) to 71 (JOY) (-22.8%). At the level of combined adverse outcome the test positive rate was reduced from 100 (PIA) to 76 (JOY) (-22.0%), thus yielding in a marked improvement of the characteristic test performance parameters. The novel, recently developed JOY software package allowed reliable evaluation of the risk for aneuploidy with increased specificity whereas sensitivity was unchanged. Our data suggest an improvement of the screening for aneuploidy when using this novel software: With an identical detection rate, the number of unnecessary invasive measures may be reduced.

ObjectiveThis study aimed to evaluate the recurrence rates after sole sentinel dissection in vulvar cancer and describe characteristics of groin recurrences.MethodsAll vulvar cancer cases between 2008 and 2014 were reviewed. Inclusion criteria were restricted to lymph node–negative patients, sole sentinel lymph node dissection (SLND), and tumor diameter less than 4 cm. In all patients, Tc-99m nanocolloid was used for preoperative SLN imaging. Regularly, planar lymphoscintigraphy and single-photon emission computed tomography with computed tomography were performed. Ultrastaging was routinely conducted on all negative lymph nodes.ResultsOf 140 vulvar cancer cases, 30 node-negative patients underwent sole SLND and met inclusion criteria. Keratinizing squamous cell carcinoma was determined in final histology in 20/30 (66.7%) patients and the mainly diagnosed tumor stage was pT1b (21/30, 70%). Three perioperative complications occurred. On average, 4.6 (1–9) SLNs were dissected per patient and 2.5 (1–6) per each groin, respectively. During a median follow-up of 43.5 (4–75) months, 5/30 (16.7%; 95% confidence interval, 7.3%–33.6%) local recurrences occurred. In addition, 2/30 (6.6%; 95% confidence interval, 1.9%–21.3%) groin recurrences were identified within a period of 12 months after the primary surgery. Both patients had large (>2 cm) midline tumors. Despite surgical as well as adjuvant treatment of the recurrent disease, both patients with groin recurrences died.ConclusionsSentinel lymph node dissection is a safe and feasible alternative in early vulvar cancer. But false-negative sentinel carry a high risk of mostly fatal groin recurrences. Especially, midline tumors larger than 2 cm have to be treated with caution, because they are mostly found in cases with groin recurrences after sole SLND.

ObjectiveNowadays, sentinel diagnostic is performed using technetium 99m (99mTc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard 99mTc-nanocolloid.MethodsWe included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using 99mTc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a 99mTc-nanocolloid–positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination.ResultsIn all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%–100%) compared with 99mTc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no 99mTc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%–96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found.ConclusionsOur results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive 99mTc-nanocolloid and worth to be evaluated in further studies.

ObjectivesThere is a risk to incidentally spread uterine malignancies, especially sarcoma, if tissue is morcellated during hysterectomy or myoma enucleation. In the last years, a worldwide discussion has been started about this problem. However, the risk seems to be very small in recent studies. This study aims at further investigating the risk of disseminating uterine malignancy during uterine surgery in a tertiary university hospital in Germany.MethodsIn a retrospective setting, all cases of uterine myometrial surgery (hysterectomies and myomectomies) in our clinic during a period of 10 years were identified using clinical databases. Histology was linked and searched for uterine malignancies. All cases were reviewed for incidental morcellation of malignant tissue.ResultsBetween 2004 and 2014, we identified 2825 cases of uterine myometrial surgery. Morcellating procedures were used in 20% of the 1402 hysterectomy procedures (280/1402) and in 13.7% of the 1423 fibroid removals (195/1423). We identified 23 uterine mesenchymal malignancies (sarcoma, n = 10; carcinosarcoma, n = 13). In 3 cases, there was no evidence or sign of a malignant disease preoperatively in a procedure with a morcellation (vaginal hysterectomy with morcellation, n = 1; open fibroid enucleation, n = 2).ConclusionsA small risk (0.35% [1/280]) of accidental morcellation during hysterectomy with morcellation was found in our study. We did not observe an occult case of sarcoma after myomectomy with morcellation (0/195), but we found 2 cases of accidental sarcoma after myomectomy without morcellation. For these reasons, minimally invasive surgery with morcellation should not be excluded a priori. The patient should be well informed about the risks and various options. The advantage of laparoscopic surgery should be balanced against the risk of the unknown spread of malignant tissue.

The proper function of the fetal heart is indispensable for the fetal development and the normal fetal growth. For prenatal medicine, Doppler sonography offers the possibility of a non-invasive method to examine the fetal cardiovascular function under normal and pathological circumstances. The role of the Doppler sonography is to identify those fetuses who have a high risk factor for developing a pre- or intrapartual asphyxia and therefore have to be delivered promptly. This study aimed at evaluating the clinical value of the intracardiac Doppler sonography (IDS) and at scrutinizing its usefulness during the supervision of the pregnancy of intrauterine growth restricted (IUGR) fetuses. In a prospective research at the Medical School of Hanover, fetal IDS was applied to 174 pregnant women between the 21 and 37 weeks of gestation (WG). The e-wave and the a-wave, the E/A ratio, and the TVI (time velocity integral) were measured at the atrioventricular (AV) valves. The PV (peak velocity) as well as the TVI were determined at both the aortic and the pulmonary valve. Normal range curves were compiled for all measured parameters. Alongside a control group with untroubled gravidity, which consisted of 153 patients, IUGR fetuses, who formed a collective of 21 patients, were Doppler sonographically examined. While the gestational age advanced, an increase of both the e-wave and the a-wave above the AV-valves could be ascertained, which lead to an E/A ratio <1. Above the semilunar valves there was indicated a slight steady increase of the TPV, the PV as well as the TVI. Normal range curves, which largely correspond to those described in the literature, were compiled for the collective of the pregnancies without pathological findings (n = 153). In comparison to the standard collective, there were no significant differences from the collective of the growth restricted fetuses (n = 21). A temporal informational advantage of pathological intracardiac Doppler values for high risk pregnancies (IUGR) could not be retraced in the examined collective. Doppler sonography traces acute and chronic deficits, which are indicated by hemodynamic changes of the fetus's blood supply. The clinical importance of IDS as regards dystrophic fetuses has to be ascertained in continuative studies: In the stage of compensatory placental insufficiency (IUGR, arterial Doppler without ARED-flow, venous Doppler without pathological findings) the IDS cannot provide an informational advantage. Contrastingly, the diagnostic potential of the IDS as a screening method of fetal cardiac insufficiency during decompensative placental insufficiency (IUGR, arterial Doppler with ARED-flow, venous Doppler normal or pathological) remains indistinct and should therefore be prospectively evaluated within this high risk group and contrastingly compared to the significance of the venous Doppler sonography (informational advantage?).

Doppler sonography of maternal vessels as a predictor for preeclampsia is an established screening method in the second trimester. Considering the first trimester its benefit has not been conclusively proven so far. Up to now the flow pattern of maternal vessels in the first trimester has only been insufficiently characterized and documented. Thus, there are only few pieces of information concerning the predictive value of the different kinds of flow patterns during the early pregnancy as regards the pathological and physiological outcome of the pregnancy. This survey aimed at evaluating the significance and the clinical importance of Doppler sonographical examinations of the Aa. uterinae during early pregnancy. It had to be analyzed whether various perfusions can be applied as a predictive value for the specific development during the pregnancy and whether therefore a risk group for pregnancy-associated hypertension can already be detected during the early pregnancy. A non-selected collective of 104 pregnant patients was examined with Doppler sonography and retrospectively divided into a standard collective and a high-risk collective. The standard collective contained 89 patients, who in the course of their pregnancy remained without any pathological findings. Fifteen patients, who were assigned to the high-risk collective, either developed a pregnancy-induced hypertension during their pregnancy or an intrauterine fetal growth retardation. The Doppler-sonographic examination of the Aa. uterinae was applied for the first time between the 6 and 8 weeks gestation (WG), then in the 9 WG, 10 WG, 11 WG, between the 12 and 14 WG, as well as between the 20 and 24 WG. Contrary to published data, there can be traced a completely transformed flow pattern in the Aa. uterinae already during the first trimester to an increasing extent. This correlates with a positive outcome of the pregnancy. There is a definite association between pathological Doppler sonography in the first third of the pregnancy and the development of a uteroplacental insufficiency as well as a pregnancy-associated hypertension (SIH) in the further course of the pregnancy. Doppler sonography is an approved method in order to become early attentive of a reduced uterine blood flow. Applying Doppler sonographic treatment of the maternal vessels, uteroplacental insufficiency can be traced at an early stage. Pregnancies, which might develop a pregnancy-associated hypertension (SIH) or a placental insufficiency, can be detected during the early pregnancy to decrease the morbidity rate and the mortality of premature newborns. Further studies in larger collectives are necessary to obtain adequate solid datasets and to further evaluate the clinical meaning and the significance concerning pathological maternal Doppler parameters.