HPV-assoziierte Genitalerkrankungen

Bei HPV-assoziierten dysplastischen Veränderungen sollte zwischen differenzierter und klassischer vulvärer intraepithelialer Neoplasie (VIN) unterschieden werden, da sich die beiden Entitäten bezüglich Ätiologie, Pathogenese und Entartungspotenzial unterscheiden. Neben der zwar komplikationsarmen Exzision oder Ablation gewinnen alternative Therapiestrategien zur Behandlung der VIN und Kondylome zunehmend an Bedeutung

Follow-up nach Therapie einer CIN, einer VIN und einer VAIN

Die Inzidenz schwerer Dysplasien und invasiver Karzinome der Zervix, Vagina und Vulva ist nach Therapie einer CIN, VIN und VAIN über einen Zeitraum von mindestens einer Dekade deutlich erhöht. Folglich ist ein sorgfältig geplantes, möglichst risikoadaptiertes Follow-up nach abgeschlossener Therapie von ausser- ordentlicher Bedeutung

IGFBP-3, a Marker of Cellular Senescence, Is Overexpressed in Human Papillomavirus-Immortalized Cervical Cells and Enhances IGF-1-Induced Mitogenesis

Human ectocervical cells, following retroviral transduction with the human papillomavirus type 16 E6/E7 oncogenes, are altered in their array of transcribed cellular genes, including increased mRNA for the insulin-like growth factor binding protein 3 (IGFBP-3). IGFBP-3 expression is associated with cellular senescence, and its addition to many cell types inhibits growth or induces apoptosis. By immunoblotting and enzyme-linked immunosorbent assay methods, we demonstrate that late-passage, immortalized E6/E7-transduced cells secrete high levels of IGFBP-3 (25 ng/ml), which represent a 500-fold increase compared to levels in early-passage, nonimmortalized transduced cells (<0.05 ng/ml). Concomitantly, these late-passage cervical cells exhibit an increase in sensitivity to IGF-1, including enhanced phosphorylation of the IGF receptor (IGF-R) and insulin receptor substrate as well as increased DNA synthesis (5-fold) and cell proliferation (3.7-fold). However, there was no change in the level of IGF-R in these cells (surface or total), and the cells did not synthesize IGF-1, indicating that these arms of the IGF pathway were independently regulated and not responsible for the augmented signaling. Consistent with a causal relationship between IGFBP-3 expression and enhanced IGF-1 responses, we found that early-passage cells could be converted to the late-passage, IGF-1-responsive phenotype by preincubation with IGFBP-3. Thus, in contrast to findings with some cell types, IGFBP-3 expression in cervical cells is associated with augmented IGF-1 signaling and cell proliferation and correlates with the timing of cellular immortalization

Therapie bei dysplastischen Veränderungen in der Gynäkologie

Die Behandlung dysplastischer Veränderungen in der Gynäkologie zielt primär auf die Verhinderung der Karzinomentstehung. Übertherapien sollten vermieden werden, da sie unter anderem das Risiko der Frühgeburtlichkeit erhöhen (Konisation) beziehungsweise Anatomie und Funktion des Genitales beeinträchtigen können. Neben Exzision und Lasertherapie kommen zunehmend auch Medikamente therapeutisch zum Einsatz

Normale und abnormale kolposkopische Befunde: Klassifikation und Bedeutung: Welche Befunde sind „gefährlich“?

Durch die Erkenntnisse der Zusammenhänge zwischen HPV-Infektion und Dysplasie ist das ideale Management in der gynäkologischen Krebsvorsorge zunehmend herausfordernd. Der Artikel erklärt die Bedeutung kolposkopischer Befunde für einen eventuellen Therapieentscheid und erläutert dabei die neuere Klassifikation

Die HPV-Impfung und -Typisierung in der Primär- und Sekundärprävention: Stellenwert in der Praxis

Mit dem HPV-Impfstoff werden Infektionen mit den häufigsten HPV-Typen primär sowie deren Folgen zum Teil auch posttherapeutisch verhindert. In der Sekundärprävention erhöht der HPV-Test in Kombination mit dem zytologischen Abstrich die Sensitivität des Erkennens zervikaler Dysplasien und erleichtert die Beurteilung des Risikopotenzials für die Entwicklung therapiebedürftiger Läsionen. Kenntnisse zum Einsatz dieser Präventivmassnahmen sind in der gynäkologischen Praxis unerlässlich

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

BACKGROUND: Accuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT. METHODS: This retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR). Post-operatively, the pathologic response was defined as absence of tumor cells (ypT0), presence of non-invasive tumor cells (ypTis) or invasive tumor cells (ypTinv). Sensitivity and specificity of US as well as false negative rate (FNR), negative predictive value (NPV) and positive predictive value (PPV) were analysed for receptor subtypes. A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. RESULTS: 50 patients (40.3%) achieved pCR, 39 (78.0%) had a corresponding cCR. Overall sensitivity was 60.8% and specificity 78.0% for US-predicted remission. NPV and FNR differed substantially between subtypes. NPV was highest (75.0%) in triple negative (TN) subtype, while FNR was low (37.5%). Therefore, pathological response was most accurately predicted for TN cancers. NPV for human-epidermal-growth-factor-receptor-2-positive/hormone-receptor-positive (HER2+/HR+) was 55.6%, for HER2+/HR- 64.3% and for HER2-/HR+ 16.7%, FNRs were 40.0%, 71.4% and 32.3%, respectively. Receptor subtypes impacted pCR significantly (p-value: 0.0033), cCR correlated positively with pCR (p-value: 0.0026). CONCLUSION: US imaging is insufficient to predict pCR with adequate accuracy. Receptor subtypes, however, affect diagnostic precision of US and pathologic outcome

Prospective Evaluation of Residual Breast Tissue After Skin- or Nipple-Sparing Mastectomy: Results of the SKINI-Trial

OBJECTIVE This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies. METHODS Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease. RESULTS Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies. CONCLUSIONS Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909