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Targeted therapy with antibody-drug conjugates (ADCs) has shown promising results in the treatment of various solid tumours. Sacituzumab-govitecan (SG), a humanised anti-Trop2 monoclonal antibody in combination with the cytotoxic topoisomerase I inhibitor SN38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 in the tumour cells. Trop2 is overexpressed in many other cancers, suggesting a broader therapeutic application of these ADCs beyond breast cancer. We are investigating the expression of Trop2 in vulvar squamous cell carcinoma (VSCC) and how this relates to molecular classification. Immunohistochemical Trop2 expression was assessed in diagnostic biopsies of VSCC using an immunoreactive score. The staining results were compared with the molecular subtype of VSCC. 57 cases were included in the study. 63.2% of VSCC were 16-ve/p53abn (HPV-independent (p53abn)) molecular subtype, 29.8% p16+ve/p53wt (HPV-associated) and 1.4% p16-ve/p53wt-(HPV-independent (p53wt)) tumors. All diagnostic biopsies (N=57) showed at least weak Trop2-expression. Expression was significantly higher, as assessed by an immunreactive score, in the HPV-associated VSCC, compared to HPV-independent. VSCC have high expression of Trop2 and represents a promising therapeutic target. Clinical trials exploring Trop2 directed ADCs such as Sacituzumab-Govitecan are warranted in this rare cancer type, including in the prognostically poor HPV-independent VSCC with a TP53-mutation (p16-ve/p53abn molecular subtype). The targetable molecule Trop2 can be easily assessed by immunohistochemistry on diagnostic biopsies from VSCC. ree version)., (The Author(s). Published by S. Karger AG, Basel.)

Vulvar carcinoma is a rare disease, meeting the criteria for a "rare cancer", but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53 , but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors.

Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S., Methods: vWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls., Results: While vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p < 0.05) in the deceased RVCL-S patient compared to the eight controls without brain pathology. One of the hypomethylated genes coded for ADAMTS-13 (p = 0.00056)., Conclusions: These findings point to an imbalance of the vWF - ADAMTS-13 axis in patients with RVCL-S, that may finally lead to an accumulation of vWF-Ag in renal and cerebral small vessels. Elevated vWF-Ag levels may serve as an early serum marker reflecting disease activity. If confirmed, therapeutic approaches might aim at an inhibition of vWF-Ag or increase of ADAMTS-13 activity in the future., (© 2024. The Author(s).)

Mesonephric-like adenocarcinomas rarely occur in the uterus and the ovary. Benign mesonephric-like (ML) proliferations and hyperplasia have been described solely within the ovary. Pathogenetic data are very limited. We report a case with microscopic focus of benign ML-proliferation in association with mucinous cystadenoma in the ovary. The immunophenotype was distinct (mucinous tumor: focal weak nuclear positivity for PAX-8, CK 7, patchy cytoplasmic positivity for p16 and negativity for estrogen receptor, CD 10, TTF-1, p53 wildtype; mesonephric component: diffusely positive for PAX-8, CK 7, luminal CD 10, TTF-1, focal staining for estrogen receptor, patchy cytoplasmic for p16, p53 wildtype). On NGS-analysis there was clonal mutation of KRAS p.G12C. The data provide additional evidence for the concept of transdifferentiation (Müllerian tissue representing Wolffian/mesonephric features on histology and immunostaining) within the pathogenesis of mesonephric proliferation of the female genital tract and demonstrate the clonal relationship between these distinct morphologic components., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Cells can adapt their active contractile properties to switch between dynamical migratory states and static homeostasis. Collective tissue surface tension, generated among others by the cortical contractility of single cells, can keep cell clusters compact, while a more bipolar, anisotropic contractility is predominantly used by mesenchymal cells to pull themselves into the extracellular matrix (ECM). Here, we investigate how these two contractility modes relate to cancer cell escape into the ECM. We compare multicellular spheroids from a panel of breast cancer cell lines with primary tumor explants from breast and cervical cancer patients by measuring matrix contraction and cellular spreading into ECM mimicking collagen matrices. Our results in spheroids suggest that tumor aggressiveness is associated with elevated contractile traction and reduced active tissue surface tension, allowing cancer cell escape. We show that it is not a binary switch but rather the interplay between these two contractility modes that is essential during this process. We provide further evidence in patient-derived tumor explants that these two contractility modes impact cancer cells' ability to leave cell clusters within a primary tumor. Our results indicate that cellular contractility is an essential factor during the formation of metastases and thus may be suitable as a prognostic criterion for the assessment of tumor aggressiveness., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Complete remission of BRAF V600E-driven ACC CUP by BRAF/MEK inhibition underscores importance of precision oncology.

In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan-Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p < 0.001) and venous infiltration (14.4 vs. 2.4%, p < 0.001). Lymph node metastasis (23.0 vs. 11.8%, p < 0.05) and parametrial involvement (47.3 vs. 17.6%, p < 0.0001) were also more common in patients with desmoplasia. The presence of desmoplasia was associated with inferior overall (80.2% vs. 94.5% hazard ratio [HR] 3.8 [95% CI 1.4-10.4], p = 0.002) and recurrence-free survival (75.3% vs. 87.3%, HR 2.3 [95% CI 1.2-4.6], p = 0.008). In addition, desmoplasia was associated with significantly less peritumoral inflammation (rho - 0.43, p < 0.0001). In summary, we link desmoplasia to a more aggressive phenotype of cervical cancer, reduced peritumoral inflammation, and inferior survival., (© 2023. The Author(s).)

Background: Histopathological examination is still the backbone for the diagnosis and treatment decision making in endometrial carcinoma (EC). The binary classification of EC into type 1 (mostly endometrioid) and type 2 (mostly serous), although still helpful, showed overlapping clinical, morphological and molecular features and was not very prognostic discriminatory for all subtypes of EC., Methods: Analysing the most recent studies dealing with the molecular classification of EC and the recommendations of the German S3-guidelines for EC., Results and Conclusion: Based on the comprehensive molecular study of The Cancer Genome Atlas Project (TCGA) four distinct molecular subtypes have been identified: EC with POLE mutation (POLEmut), with loss of mismatch repair proteins (MMR deficiency; dMMR), or with TP53 mutation (p53mut) and without any of these alterations, termed NSMP (no specific molecular profile). The molecular classification of EC presents a morphomolecular approach, based on histopathological evaluation (tumor diagnosis, subtyping, grading), immunohistochemistry (MMR, p53) and molecular analyses for POLE. The incorporation of this molecular classification is recommended for clinical use by the World Health Organisation (WHO) as well as many national guidelines and international societies. Due to the heterogeneity of NSMP-EC, which is the largest molecular group, additional research is indicated to further characterise these tumors., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Pregnant women are also susceptible to SARS-CoV-2. Although an infection of the placenta may be rare, pregnancy may occasionally be affected by intrauterine failure. The knowledge of placental morphology on sudden intrauterine demise is still limited., Methods: Fetal and placental tissue of two cases of sudden intrauterine death in the second trimester were analysed morphologically and by immunohistochemistry. One case was evaluated by RT-PCR., Results: Both mothers were tested positive for the Alpha variant of SARS-CoV-2 but were oligosymptomatic for COVID-19. Unexpected sudden intrauterine death (SIUD) occurred at 15 + 2 and 27 + 3 weeks of gestation. One fetus demonstrated an intrauterine growth restriction. No malformations nor inflammatory changes were observed in either fetus on autopsy. In contrast to the placentas, the fetal tissue was negative for SARS-CoV-2 on immunohistochemical and RT-PCR analyses. Macroscopically, the placentas showed an increased consistency with a white, reticular cutting surface covering about 95% of the whole placenta. Only very focal histiocytic chronic intervillositis was noted histologically. Massive perivillous fibrin deposits with extensive necroses of the villous trophoblast were present in more than 90% of the placental tissue. Immunohistochemical staining was strong and diffusely positive for SARS-CoV-2 in the villous trophoblast and rarely within the villous stromal cells. Placental SARS-CoV-2 infection was confirmed by RT-PCR., Conclusion: Sudden intrauterine death may occur in mothers who are oligosymptomatic for COVID-19. Acute placental failure is responsible for SIUD, demonstrated by massive perivillous fibrin deposits and extensive necroses of the villous trophoblast with SARS-CoV-2-positivity based on immunohistochemical staining and RT-PCR. Detailed histopathological examination of placental and fetal tissue is mandatory to verify SARS-CoV-2 and to evaluate the pathogenesis and functionality of this disease., (© 2022. The Author(s).)

Purpose: Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis., Methods: The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis., Results: The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p < 0.001), more frequently diagnosed at an advanced stage >pT3 (78.5% (219/279) versus 42.8% (87/203); p < 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p < 0.02) with a 4.6-fold higher rate of > 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p < 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups., Conclusion: OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Uterine sarcomas are a heterogeneous group of rare malignancies. Mostly (40-50%), they are leiomyosarcomas, followed by endometrial stromal sarcomas (ESS), low-grade (LG) and high-grade (HG), as well as undifferentiated sarcoma of the uterus (UUS) and adenosarcomas (AS). Other, non-organ-specific tumours such as NTRK-rearranged spindle cell neoplasia, perivascular epithelioid cell tumour (PEComa) and inflammatory myofibroblastic tumour (IMT) are extremely difficult to differentiate.In the most recent WHO classification, endometrial stromal tumours are subdivided as follows: benign, expansively growing endometrial stromal nodule (ESN) with sharp demarcation, the histologically similar-looking LG-ESS with infiltrative growth, the highly malignant HG-ESS and, as a diagnosis of exclusion, the highly aggressive UUS lacking specific lines of differentiation. LG-ESS can be differentiated from HG-ESS in most cases histomorphologically and immunohistochemically, but molecular investigations are necessary in individual cases. HG-ESS can be divided into 4 subtypes (YWHAE/NUTM2 fusion low-grade component, YWHAE/NUTM2 fusion high-grade component, ZC3H7B-BCOR fusion or BCOR-ITD) on the basis of molecular findings. Prognostically unfavourable factors in AS are severe sarcomatous overgrowth, deep myometrial invasion, high-grade histology and lymphatic vessel invasion. Tumours with NTRK fusion are immunohistochemically positive for S100 and TRK. PEComas express cathepsin K and HMB45, as well as TFE3 when translocation is present. Almost every IMT shows an alteration in the ALK gene In the case of overlapping morphology and simultaneous therapeutic and prognostic relevance, it is becoming increasingly important to verify or confirm the suspected histomorphological diagnosis by immunohistochemical and possibly molecular investigations., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Epithelial-mesenchymal transition (EMT) is associated with increased metastatic spread and poor prognosis. Data on vulvar carcinoma are limited., Methods: Thirty-two cases of squamous cell carcinoma of the vulva (16 with and 16 without inguinal lymph node metastases) and their lymph node deposits were evaluated for immunohistochemical expression of EMT markers (vimentin, cyclin D1, e-cadherin), p16, p53 and Ki-67. Results of EMT-immunostainings were compared to lymph node involvement and expression of p53 and p16. The micro-anatomical staining pattern for EMT markers comparing the tumor center with the front of invasion was analysed in each tumor., Results: There was no difference in the expression of EMT markers between node negative and node positive tumors. Staining for vimentin and cyclin D1 was seen within tumor cells at the front of invasion in 100 and 84.4% of the tumors, respectively. The majority of cases (68.7%) showed negative or reduced staining for e-cadherin in this micro-anatomical localization. Tumor cells within the lymph node metastases showed positive staining for e-cadherin in 75% and for cyclin D1 in 49% of the cells but were negative for vimentin in 13 out of 16 cases (81.3%). Tumors with aberrant p53 staining represented a non-significant higher vimentin but significantly higher cyclin D1 expression at the front of invasion than those with p53 wild-type pattern., Conclusion: The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining., (© 2021. The Author(s).)

The 2020 WHO Classification defines the spindle cell, epithelioid, and myxoid variants as subtypes of uterine leiomyosarcomas (LMS). Presence of cellular atypia (size variation of polymorphic nuclei > 2-3:1), tumor cell necroses, and mitotic count (usually ≥ 10 MF/10 HPF) are still the key features for diagnostic separation from uterine leiomyomas. Preanalytic variables, staining quality, as well as intralesional geographic distribution may affect the mitotic count. Smooth muscle tumors of uncertain malignant potential (STUMP) still exist as a not yet well-characterized diagnostic entity. Immunohistochemical stains against p16, p53, Ki-67, and WT‑1 may aid differential diagnosis in selected cases. Diagnostic molecular pathology is not yet relevant for diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The 2020 WHO classification is focused on the distinction between HPV-associated and HPV-independent squamous cell carcinoma of the lower female genital organs. Differentiating according to HPV association does not replace the process of grading; however, the WHO classification does not recommend any specific grading system. VIN are also differentiated according to whether they are HPV(p16)-associated. HPV-independent adenocarcinoma (AC) of the cervix uteri has an unfavorable prognosis. Immunohistochemical p16 expression is considered to be a surrogate marker for HPV association. HPV-associated AC of the cervix uteri is determined using the prognostically relevant Silva pattern., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The new WHO classification of tumors of the female genitalia entails some changes, especially those of prognostic and therapeutic relevance: there is a return to the term borderline tumor. Implants are again subdivided into noninvasive implants of the epithelial or desmoplastic type as before. Invasive extraovarian implants are classified as low-grade serous carcinoma (LGSC). Former seromucinous carcinomas are now classified as endometrioid carcinomas (seromucinous subtype). New entities of ovarian carcinomas are mesonephric-like adenocarcinoma, undifferentiated and dedifferentiated carcinoma, and mixed carcinoma. The classification of neuroendocrine neoplasms is analogous to that of pulmonary and gastrointestinal neuroendocrine neoplasms, regardless of their location. Endometrioid endometrial carcinoma can be classified into four molecular subtypes, which have significant prognostic significance. New subtypes include mucinous carcinoma of the intestinal type and mesonephric-like adenocarcinoma. Stromasarcomas of the endometrium are further subclassified based on specific molecular alterations. Adenocarcinomas (ACs) and squamous cell carcinomas (PECs) of the lower female genital tract are distinguished from HPV-associated and HPV-independent carcinomas. Block-like staining for p16 is the accepted surrogate immunohistochemical marker. Grading has not been reported for PEC. For HPV-associated AC of the cervix uteri, prognostic assessment is based on the pattern of invasion (so-called Silva pattern). Serous carcinomas in the cervix uteri are endometrial carcinomas with cervical infiltration.

The handling and reporting of resected lymph nodes in gynecologic cancer follows the recommendations of the German national guidelines and the recommendations of the International Collaboration of Cancer Reporting (ICCR) and the International Society of Gynecologic Pathologists (ISGyP). The definitions of micrometastases and isolated tumor cells are in accordance with the definition of the UICC (Union Internationale Contre le Cancer) and TNM system. Both findings must be reported as part of the pathology report and final tumor classification. It is mandatory to examine all excised lymph nodes with complete processing of all nodes up to 0.3 cm and slicing of all larger nodes in 0.2-cm wide intervals with complete processing of all lamellae. The amount of the resected lymph nodes in correlation to positive nodes, the metric dimension of the largest lymph node metastasis per lymph node region, and the presence of extracapsular extension of the lymph node deposits must be part of the pathology report. The handling and cutting of sentinel lymph nodes are similar to nonsentinel nodes. Within frozen section analyses and final processing from paraffin-embedded sentinel nodes, all nodes should be examined by three-step sections with an interval of about 200 µm. In cases of negative sentinel nodes on H&E staining, immunohistochemical ultrastaging should be performed.

Purpose: Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube., Methods: Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes., Results: The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology., Conclusion: The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

Objectives: (A) To introduce a new technique for vaginal fluid sampling (biocompatible synthetic fiber sponge) and (B) evaluate the collected vaginal fluid interleukine-6 (IL-6 vag )-concentration as a new diagnostic tool for daily monitoring of intrauterine inflammation after preterm premature rupture of membranes (PPROM). Secondary objectives were to compare the potential to predict an intrauterine inflammation with established inflammation parameters (e.g., maternal white blood cell count)., Methods: This prospective clinical case-control diagnostic accuracy multicenter study was performed with women after PPROM (gestational age 24.0/7 - 34.0/7 weeks). Sampling of vaginal fluid was performed once daily. IL-6 vag was determined by electrochemiluminescence-immunoassay-kit. Neonatal outcome and placental histology results were used to retrospectively allocate the cohort into two subgroups: 1) inflammation and 2) no inflammation (controls)., Results: A total of 37 cases were included in the final analysis. (A): Measurement of IL-6 was successful in 86% of 172 vaginal fluid samples. (B): Median concentration of IL-6 vag in the last vaginal fluid sample before delivery was significantly higher within the inflammation group (17,085 pg/mL) compared to the controls (1,888 pg/mL; p=0.01). By Youden's index an optimal cut-off for prediction an intrauterine inflammation was: 6,417 pg/mL. Two days before delivery, in contrast to all other parameters IL-6 vag remained the only parameter with a sufficient AUC of 0.877, p<0.001, 95%CI [0.670-1.000]., Conclusions: This study established a new technique for vaginal fluid sampling, which permits assessment of IL-6 vag concentration noninvasively in clinical daily routine monitoring., (© 2021 Gregor Seliger et al., published by De Gruyter, Berlin/Boston.)

Background: Obesity is a major public health problem with an increasing prevalence reaching pandemic levels. The incidence and mortality for colorectal cancer is augmented in overweight and obese individuals. Previous studies demonstrated an impaired number, phenotype and functionality of natural killer (NK) cells under obese conditions. So far, the influence of obesity on NK cells in colorectal cancer tissue remained unclear. Therefore, the aim of the study was to investigate the occurrence and localization of NK cells in colorectal tumors of normal weight and diet-induced obese rats., Methods: Wistar rats were fed a normal-fat diet (control) or a high-fat diet (HFD) to induce obesity. In half of the experimental groups azoxymethane (AOM) was injected to induce colorectal cancer. Tumors in colon and rectum were histopathologically classified in adenomas and adenocarcinomas and immunohistologically stained with the rat NK cell marker CD161. Occurrence and localization of NK cells were analyzed and quantified in the tunica mucosa and tunica submucosa of colorectal adenomas and the tunica submucosa of colorectal adenocarcinomas., Results: NK cells are localized in the tunica mucosa and the tunica submucosa of colorectal tumors with NK cell accumulations as follicle-like aggregates especially in regions of the lamina muscularis mucosae and the lamina propria mucosae of the tunica mucosa as well as in regions of the tunica submucosa adjacent to the lamina muscularis mucosae. Although not statistically significant, the CD161 staining was clearly reduced in the tunica mucosa of colorectal tumors of rats fed a HFD compared to rats fed a control diet. Moreover, the CD161 staining in the tunica mucosa was positively correlated with the final body weight of AOM-treated rats independent of the supplied diet., Discussion: For the first time, these results provide information about the localization and quantity of NK cells in colorectal tumor tissue of rats fed a control diet or high-fat diet. The slight reduction of NK cell number in colorectal tissue of rats fed a high-fat diet may contribute to an impaired tumor defense and the increased colorectal tumor outcome in diet-induced obese rats., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Purpose To evaluate whether intraoperative ultrasound-guided detection and resection of the uterine scar during repeat/second cesarean can reduce the number of scars and improve uterine scar architecture. Materials and methods A prospective controlled clinical intervention trial was performed with the following groups: control group 1 (CS1-G): first cesarean; control group 2 (CS2-G): second cesarean utilizing the usual procedure and intervention group (Int-G): repeat/second cesarean with intervention. Transvaginal ultrasound scans were performed 6-9 months after each cesarean. Both primary (double scarring rate) and secondary outcomes [deficiency ratio=d/(b+d)] were analyzed. The deficiency ratio describes the thinning of the remaining myometrium (d=residual myometrial thickness) over the "apparent" defect (b=scar depth). Results In total, 124 of the 156 recruited women were examined, eight were excluded from analysis. The double scarring rate decreased from 42.9% (12/28) in CS2-G to 7.1% (2/28) in the Int-G [difference: 35.8%; 95% confidence interval (CI) (13.2, 54.5); P=0.002]. Two-way analysis of variance (ANOVA) revealed a significant difference between CS2-G and the Int-G in the deficiency ratio adjusted for elective/primary cesareans, with thicker remaining myometrium over the scar defect in the Int-G [difference: -0.24; 95% CI (-0.34, -0.15); P<0.001]. Conclusion Ultrasound-guided resection of the uterine scar area during repeat cesareans reduces the scarring rate and improves thickness of the remaining myometrium as detected by ultrasonography 6-9 months postoperatively.

Objectives: The purpose of this study was to assess, if the biomechanical properties of the lower uterine segment (LUS) in women with a previous cesarean section (CS) can be determined by ultrasound (US) elastography. The first aim was to establish an ex-vivo LUS tensile-stress-strain-rupture(break point) analysis with the possibility of simultaneously using US elastography. The second aim was to investigate the relationship between measurement results of LUS stiffness using US elastography in-/ex-vivo with results of tensile-stress-strain-rupture analysis, and to compare different US elastography LUS-stiffness-measurement methods ex-vivo., Study Design: An explorative experimental, in-/ex-vivo US study of women with previous CS was conducted. LUS elasticity was measured by point Shear Wave Elastography (pSWE) and bidimensional Shear-Wave-Elastography (2D-SWE) first in-vivo during preoperative examination within 24 h before repeat CS (including resection of the thinnest part of the LUS = uterine scar area during CS), second within 1 h after operation during the ex-vivo experiment, followed by tensile-stress-strain-rupture analysis. Pearson's correlation coefficient and scatter plots, Bland-Altman plots and paired T-tests, were used., Results: Thirty three women were included in the study; elastography measurements n = 1412. The feasibility of ex-vivo assessment of LUS by quantitative US elastography using pSWE and 2D-SWE to detect stiffness of LUS was demonstrated. The strongest correlation with tensile-stress-strain analysis was found in the US elastography examination carried out with 2D-SWE (0.78, p < 0.001, 95%CI [0.48, 0.92]). The laboratory experiment illustrated that, the break point - as a surrogate marker for the risk of rupture of the LUS after CS - is linearly dependent on the thickness of the LUS in the scar area (Coefficient of correlation: 0.79, p < 0.001, 95%CI [0.55, 0.91]). Two extremely stiff LUS-specimens (outlier or extreme values) rupture even at less stroke/strain than would be expected by their thickness., Conclusion: This study confirms that US elastography can help in determining viscoelastic properties of the LUS in women with a previous CS. The data from our small series are promising. However whether individual extreme values of high stiffness and consecutive restricted biomechanical resilience can explain the phenomenon of rupture during TOLAC in cases of LUS with adequate thickness remains a question which prospective trials have to analyze before US elastography can be introduced into clinical practice., (Copyright © 2018 Elsevier B.V. All rights reserved.)