Evaluating the value of a 3D printed model for hands-on training of gynecological pelvic examination.

BACKGROUND: Simulation in the field of gynecological pelvic examination with educational purposes holds great potential. In the current manuscript we evaluate a 3D printed model of the female pelvis, which improves practical teaching of the gynecological pelvic examination for medical staff. METHODS: We evaluated the benefit of a 3D printed model of the female pelvis (Pelvisio®) as part of a seminar ("skills training") for teaching gynecological examination to medical students. Each student was randomly assigned to Group A or B by picking a ticket from a box. Group A underwent the skills training without the 3D printed model. Group B experienced the same seminar with integration of the model. Both groups evaluated the seminar by answering five questions on Likert scales (1-10, 1 = "very little" or "very poor", 10 equals "very much" or "very good"). Additionally, both groups answered three multiple-choice questions concerning pelvic anatomy (Question 6 to 8). Finally, Group B evaluated the 3D printed model with ten questions (Question 9 to 18, Likert scales, 1-10). RESULTS: Two of five questions concerning the students' satisfaction with the seminar and their gained knowledge showed statistically significant better ratings in Group B (6.7 vs. 8.2 points and 8.1 vs. 8.9 points (p < 0.001 and p < 0.009). The other three questions showed no statistically significant differences between the traditional teaching setting vs. the 3D printed model (p < 0.411, p < 0.344 and p < 0.215, respectively). The overall mean score of Question 1 to 5 showed 8.4 points for Group B and 7.8 points for Group A (p < 0.001). All three multiple-choice questions, asking about female pelvic anatomy, were answered more often correctly by Group B (p < 0.001, p < 0.008 and p < 0.001, respectively). The mean score from the answers to Questions 9 to 18, only answered by Group B, showed a mean of 8.6 points, indicating, that the students approved of the model. CONCLUSION: The presented 3D printed model Pelvisio® improves the education of female pelvic anatomy and examination for medical students. Hence, training this pivotal examination can be supported by a custom designed anatomical model tailored for interactive and explorative learning.

Evaluating a novel 3D printed model for simulating Large Loop Excision of the Transformation Zone (LLETZ).

BACKGROUND: Electrosurgical excisions are common procedures for treating cervical dysplasia and are often seen as minor surgeries. Yet, thorough training of this intervention is required, as there are considerable consequences of inadequate resections, e.g. preterm birth, the risk of recurrence, injuries and many more. Unfortunately, there is a lack of sufficiently validated possibilities of simulating electrosurgeries, which focus on high fidelity and patient safety. METHODS: A novel 3D printed simulator for examination and electrosurgical treatment of dysplastic areas of the cervix was compared with a conventional simulator. Sixty medical students experienced a seminar about cervical dysplasia. Group A underwent the seminar with the conventional and Group B with the novel simulator. After a theoretical introduction, the students were randomly assigned by picking a ticket from a box and went on to perform the hands-on training with their respective simulator. Each student first obtained colposcopic examination training. Then he or she performed five electrosurgical excisions (each). This was assessed with a validated score, to visualize their learning curve. Furthermore, adequate and inadequate resections and contacts between electrosurgical loop and vagina or speculum were counted. Both groups also assessed the seminar and their simulator with 18 questions (Likert-scales, 1-10, 1 = strongly agree / very good, 10 = strongly disagree / very bad). Group B additionally assessed the novel simulator with four questions (similar Likert-scales, 1-10). RESULTS: Nine of 18 questions showed statistically significant differences favoring Group B (p < 0.05). Group B also achieved more adequate R0-resections and less contacts between electrosurgical loop and vagina or speculum. The learning curves of the performed resections favored the novel simulator of Group B without statistically significant differences. The four questions focusing on certain aspects of the novel simulator indicate high appreciation of the students with a mean score of 1.6 points. CONCLUSION: The presented novel simulator shows several advantages compared to the existing model. Thus, novice gynecologists can be supported with a higher quality of simulation to improve their training and thereby patient safety.

A 3D printed model of the female pelvis for practical education of gynecological pelvic examination.

BACKGROUND: Pelvic palpation is a core component of every Gynecologic examination. It requires vigorous training, which is difficult due to its intimate nature, leading to a need of simulation. Up until now, there are mainly models available for mere palpation which do not offer adequate visualization of the concerning anatomical structures. In this study we present a 3D printed model of the female pelvis. It can improve both the practical teaching of gynecological pelvic examination for health care professionals and the spatial understanding of the relevant anatomy. METHODS: We developed a virtual, simplified model showing selected parts of the female pelvis. 3D printing was used to create a physical model. RESULTS: The life-size 3D printed model has the ability of being physically assembled step by step by its users. Consequently, it improves teaching especially when combining it with commercial phantoms, which are built solely for palpation training. This is achieved by correlating haptic and visual sensations with the resulting feedback received. CONCLUSION: The presented 3D printed model of the female pelvis can be of aid for visualizing and teaching pelvic anatomy and examination to medical staff. 3D printing provides the possibility of creating, multiplying, adapting and sharing such data worldwide with little investment of resources. Thus, an important contribution to the international medical community can be made for training this challenging examination.

Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer.

Ovarian cancer is the second most common gynecological malignancy in women. More than 70% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer.

Introducing a novel model for simulating large loop excision of the transformation zone (LLETZ) using 3D printing technique.

PURPOSE: Electrosurgery is the gold-standard procedure for the treatment of cervical dysplasia. The quality of the outcome depends on the accuracy of performance, which underlines the role of adequate training of surgeons, especially, as this procedure is often performed by novice surgeons. According to our knowledge, medical simulation has up until now lacked a model, which focuses on realistically simulating the treatment of cervical dysplasia with the concerning anatomy. METHODS AND RESULT: In our work, we present a model created using 3D printing for holistically simulating diagnostic, as well as surgical interventions of the cervix, as realistically as possible. CONCLUSION: This novel simulator is compared to an existing model and both are evaluated. By doing so, we aim to provide novice gynecologists with standardized and high-quality simulation models for practicing to improve their proficiency.

Total Mesometrial Resection With (Neo)Adjuvant Chemotherapy in Locally Advanced Cervical Cancer: A Tumor Response Score.

BACKGROUND/AIM: There is a lack of data concerning the surgical treatment of locally advanced squamous cell carcinoma of the uterine cervix (LACC) with neoadjuvant and adjuvant chemotherapy (NACT, ACT) as well as total mesometrial resection (TMMR). The aim of the study was to present a novel approach for treating LACC using a tumor response score for NACT. PATIENTS AND METHODS: A total of 12 patients with LACC were treated with NACT [cisplatin, ifosfamide, paclitaxel (TIP)], TMMR and ACT containing TIP. To measure the response during NACT, we scored i) the maximum tumor diameter (maxTD) in gynecological examination, ii) the MRI for radiologic maxTD, iii) the tumor volume and iv) the squamous cell carcinoma antigen before and after two applications of TIP. RESULTS: TIP reduced all score-parameters in 10 of 12 patients (p<0.005). We found a possible reduction of lymph node metastasis in 72.7%. The proposed score detected sufficient and insufficient tumor response. CONCLUSION: TIP followed by TMMR with ACT could be a possibility for patients denying radiochemotherapy. The tumor response score can detect patients with inadequate benefit from NACT.

Implementation of robotic gynecological surgery in a German University Hospital: patient safety after 110 procedures.

PURPOSE: Robotic surgery represents the latest development in the field of minimally invasive surgery and offers many technical advantages. Despite the higher costs, this novel approach has been applied increasingly in gynecological surgery. Regarding the implementation of a new operative method; however, the most important factor to be aware of is patient safety. In this study, we describe our experience in implementing robotic surgery in a German University Hospital focusing on patient safety after 110 procedures. METHODS: We performed a retrospective analysis of 110 consecutive robotic procedures performed in the University Hospital of Würzburg between June 2017 and September 2019. During this time, 37 patients were treated for benign general gynecological conditions, 27 patients for gynecological malignancies, and 46 patients for urogynecological conditions. We evaluated patient safety through standardized assessment of intra- and postoperative complications, which were categorized according to the Clavien-Dindo classification. RESULTS: No complications were recorded in 90 (81.8%) operations. We observed Clavien-Dindo grade I complications in 8 (7.3%) cases, grade II complications in 5 (4.5%) cases, grade IIIa complications in 1 case (0.9%), and grade IIIb complications in 6 (5.5%) cases. No conversion to laparotomy or blood transfusion was needed. CONCLUSION: Robotic surgery could be implemented for complex gynecological operations without relevant problems and was accompanied by low complication rates.

Role of Renin-Angiotensin-System in Human Breast Cancer Cells: Is There a Difference in Regulation of Angiogenesis between Hormone-Receptor Positive and Negative Breast Cancer Cells?

Objective This study examined the role of the RAS in human breast cancer cells to question if there are differences between HR-positive and HR-negative cells with regard to regulation of VEGF. Methods Expression of different RAS components in hormone receptor (HR)-positive and HR-negative breast cancer cells was investigated using RT-PCR. Different stimulation protocols with different RAS inhibitors were used to investigate the effect on VEGF expression. Angiotensin II-dependent expression of VEGF was quantified by real time PCR. In addition, the effect of intrinsic RAS was studied performing siRNA knockdown of angiotensinogen (AGT). Statistical analysis were calculated using IBM SPSS Statistics Version 21. Results Expression of AT 1 R, AT 2 R, AGT and ACE was shown in HR-positive and HR-negative breast cancer cell lines. Extrinsic stimulation with angiotensin II increased VEGF significantly. After treatment with captopril or AT 1 R-inhibitor candesartan, VEGF-expression decreased significantly in HR-positive and HR-negative cell lines. However, inhibition of AT 2 R using PD 123,319 did not show any significant changes of VEGF. After prevention of intrinsic angiotensin II, extrinsic angiotensin II as well as the combination with inhibitors of the receptors caused a significant reduction of VEGF. Surprisingly, the overall effect of the RAS after knockdown of AGT revealed a significant increase of VEGF in HR-positive cells at any time while a significant decrease was observed in HR-negative cells after 144 hours incubation. Conclusion The RAS-dependent regulation of VEGF between HR-positive and HR-negative breast cancer cells seems do be different. These findings provide evidence for a possible future therapeutic strategy.

Nectin-2 in ovarian cancer: How is it expressed and what might be its functional role?

Nectin-2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin-2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin-2 and CD31 using immunohistochemistry. Gene expression of Nectin-2 was quantified by real-time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin-2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin-2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin-2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin-2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin-2 which was reversed by VEGF-inhibition. In addition, Nectin-2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin-2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF-induced Nectin-2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production.

Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?

BACKGROUND: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. METHODS: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. RESULTS: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. CONCLUSIONS: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.

Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome.

In a developing human corpus luteum, a closely regulated cellular communication system exists between the luteal steroidogenic cells and endothelial cells. This system guaranties the vascularization process during luteal formation. The process is combined with rapid release of large amounts of progesterone into the bloodstream. The regulation of endothelial proliferation and permeability by LH and human chorionic gonadotropin (hCG) is integral to this process. On the cellular level, endothelial permeability is regulated by intercellular junctions, such as adherens junctions (AJ) and tight junctions (TJ), which act as zipper-like structures between interacting endothelial cells. Several cell junctional proteins are localized to the corpus luteum, including Occludin, Nectin 2, Claudin 1, and Claudin 5, as well as, vascular endothelial (VE)-Cadherin. It has been assumed that regulation of AJ- and TJ-proteins is of particular importance for permeability, and accordingly, for the functionality of the corpus luteum in early pregnancy, because treatment with hCG induces downregulation of juntional proteins in the luteal vessels. The effect of hCG on the adhesive molecules is mediated by VE growth factor (VEGF). On a functional level, the hCG-dependent and VEGF-mediated decrease in junctional proteins causes a decrease in the density of cell-cell closure and, accordingly, an increase in endothelial permeability. In doing so, the different junctional proteins are not only directly influenced by VEGF but also interact among themselves and influence each other reciprocally. Disturbances in this strictly, regulated interactions may explain the development of pathologies with increased vascular permeability, such as the ovarian hyperstimulation syndrome.

Temperature-dependence of yadBC phenotypes in Yersinia pestis.

YadB and YadC are putative trimeric autotransporters present only in the plague bacterium Yersinia pestis and its evolutionary predecessor, Yersinia pseudotuberculosis. Previously, yadBC was found to promote invasion of epithelioid cells by Y. pestis grown at 37 °C. In this study, we found that yadBC also promotes uptake of 37 °C-grown Y. pestis by mouse monocyte/macrophage cells. We tested whether yadBC might be required for lethality of the systemic stage of plague in which the bacteria would be pre-adapted to mammalian body temperature before colonizing internal organs and found no requirement for early colonization or growth over 3 days. We tested the hypothesis that YadB and YadC function on ambient temperature-grown Y. pestis in the flea vector or soon after infection of the dermis in bubonic plague. We found that yadBC did not promote uptake by monocyte/macrophage cells if the bacteria were grown at 28 °C, nor was there a role of yadBC in colonization of fleas by Y. pestis grown at 21 °C. However, the presence of yadBC did promote recoverability of the bacteria from infected skin for 28 °C-grown Y. pestis. Furthermore, the gene for the proinflammatory chemokine CXCL1 was upregulated in expression if the infecting Y. pestis lacked yadBC but not if yadBC was present. Also, yadBC was not required for recoverability if the bacteria were grown at 37 °C. These findings imply that thermally induced virulence properties dominate over effects of yadBC during plague but that yadBC has a unique function early after transmission of Y. pestis to skin.

Local Renin-Angiotensin system in the reproductive system.

The renin-angiotensin system (RAS) is well known as regulator of electrolytes and blood pressure. Besides this function, there are numerous studies supporting the idea of a local tissue RAS. This system controls the local activity of the different RAS family members, especially of the functional proteins Angiotensin II and Angiotensin (1-7). Those antagonistically acting proteins have been described to be expressed in different organ systems including the human reproductive tract. Therefore, this local RAS has been suspected to be involved in the control and regulation of physiological and pathological conditions in the female reproduction tract. This review of the available literature summarizes the physiological influence of the RAS on the follicular development, ovarian angiogenesis, and placental- and uterine function. In addition, in the second part the role of the RAS concerning ovarian- and endometrial cancer becomes elucidated. This section includes possible novel therapeutic strategies via inhibition of RAS-mediated tumor growth and angiogenesis. Looking at a very complex system of agonistic and antagonistic tissue factors, it may be supposed that the RAS in the female reproduction tract will be of rising scientific interest in the upcoming years.

Human chorionic gonadotropin controls luteal vascular permeability via vascular endothelial growth factor by down-regulation of a cascade of adhesion proteins.

OBJECTIVE: To study the functional interactions of junctional proteins acting as regulators of vascular permeability in the human corpus luteum. We investigated the role of vascular endothelial (VE)-cadherin, nectin 2, and claudin 5 as controllers of vascular endothelial cell permeability. DESIGN: Performing immunohistochemical dual staining, we colocalized the above-mentioned proteins in the human corpus luteum. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Using a granulosa-endothelial coculture system, we revealed that hCG-treatment down-regulates VE-cadherin, nectin 2, and claudin 5 in endothelial cells via vascular endothelial growth factor (VEGFA). RESULT(S): Furthermore, the interaction of VE-cadherin, nectin 2, and claudin 5 was investigated by silencing these proteins that perform siRNA knockdown. Interestingly, knockdown of VE-cadherin and claudin 5 induced a decrease of the respective other protein. This down-regulation was associated with changed rates of vascular permeability: hCG induced a VEGFA-dependent down-regulation of VE-cadherin, nectin 2, and claudin 5, which increased the endothelial permeability in the coculture system. Furthermore, knockdown of VE-cadherin, nectin-2, and claudin 5 also resulted in a consecutive increase of endothelial permeability for each different protein. CONCLUSION(S): These results demonstrate for the first time that VE-cadherin, nectin 2, and claudin 5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum.

VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5.

OBJECTIVE: To evaluate the role of VEGF-dependent Claudin 5 production for the development of ascites via influencing endothelial permeability in peritoneal tissue of ovarian cancer patients. METHODS: This study investigates the mechanisms of formation of ascites in ovarian cancer patients, performing RT-PCR, VEGF-ELISA and immunohistochemical dual staining for CD31 and Claudin 5. In addition, in order to analyze the connectivity of VEGF, Claudin 5, and endothelial permeability, an endothelial cell/ovarian cancer cell-co-culture-system was established and evaluated performing Western blot analysis and a permeability assay. RESULTS: Firstly, VEGF-gene expression was demonstrated for all ovarian cancer and peritoneal biopsies. In addition, quantification of VEGF in the serum and ascites of ovarian cancer patients revealed significantly increased values. We subsequently demonstrated Claudin 5 production in the peritoneal vessels, which was weaker than in the vessels of the controls. Evaluation of endothelial permeability finally showed a VEGF-dependent regulation via Claudin 5 suggesting a mechanism for the development of ascites in ovarian cancer patients. CONCLUSION: VEGF induces ascites in ovarian cancer patients. This instance happens due to increased peritoneal permeability, caused by downregulation of the tight junction protein Claudin 5 in the peritoneal endothelium.

Is there a role of the local tissue RAS in the regulation of physiologic and pathophysiologic conditions in the reproductive tract?

The renin-angiotensin system is well known as a systemic endocrine pathway that regulates blood pressure and salt-water metabolism. In addition to the systemic renin-angiotensin system there is evidence in different species for the presence of a local tissue renin-angiotensin system, which allows local production of the bioactive peptides angiotensin II and angiotensin (1-7). The local renin-angiotensin system has been found in a variety of tissues including tissue of the human reproductive tract. Thus, it was suspected that it may have important functions in the local hormonal microenvironment. Here, a systematic literature search was undertaken to review whether there is evidence for regulatory functions of the local tissue renin-angiotensin system in the human reproductive tract under physiological and pathological conditions.

Exacerbation of a maternal hiatus hernia in early pregnancy presenting with symptoms of hyperemesis gravidarum: case report and review of the literature.

CASE REPORT: We report on a 30-year old woman presenting with symptoms of hyperemesis gravidarum and subsequent vomiting at the end of the first trimester (12 + 0 weeks of gestation). The patient was initially presented with nausea and vomiting, without any signs or symptoms of intra-abdominal disorders. On the 2nd day, symptoms became worse and she complained right sided upper abdominal pain, therefore abdominal ultrasound was performed, showing no remarkable findings, explaining the disorder. Clinical symptoms increased and the patient complained suddenly severe dyspnoea and intractable cough. Therefore, immediately an X-ray examination of the thorax was performed showing a severe left sided diaphragmatic hiatus hernia with consecutive displaced stomach into the thoracic cavity, making immediate surgical intervention necessary. DISCUSSION: Diaphragmatic hernias complicating pregnancy are a rare event, they normally occur in later periods of pregnancy due to the rising intra-abdominal pressure mainly caused by the enlargement of the uterus. Also maternal diaphragmatic hernias during pregnancy are usually associated with minor complains. However, they can be life-threatening, due to mediastinal shift and cardio-respiratory failure. The majority of maternal diaphragmatic hernias complicating pregnancies occur in antenatal period, most of them in the third trimester. More than 90% of maternal diaphragmatic hernias complicating pregnancy are localized on the left side of the maternal diaphragma. We present a case of an early onset life-threatening maternal diaphragmatic hernia. Usually, maternal diaphragmatic hernias become clinically obvious in advanced stage of pregnancy, in contrast hyperemesis gravidarum is normally occurring in the first trimester and is usually self-limiting. Guiding symptoms for hyperemesis gravidarum are nausea and vomiting, but these clinical findings can also be unspecific symptoms of a maternal diaphragmatic hernia. Therefore, especially mild variants of maternal diaphragmatic hernias in early pregnancy can be misdiagnosed as hyperemesis gravidarum. Nevertheless, the rising intra-abdominal pressure while vomiting obviously can trigger exacerbation of a pre-existing maternal diaphragmatic hernia. We therefore speculate that there could be an association between physiological changes in early pregnancy, for example in gastric motility, and the exacerbation of the pre-existing maternal hiatus hernia. CONCLUSION: Hence a diaphragmatic hernia should always be excluded, if symptoms of nausea and vomiting are intractable, mediastinal shift with dyspnoea occurs, failure of conservative treatment especially after 20th week of gestation and in late onset of assumed hyperemesis gravidarum.

Impact of guideline conformity on breast cancer therapy: results of a 13-year retrospective cohort study.

BACKGROUND: To date, few studies have investigated whether the implementation of national breast cancer guidelines fulfills the goal to optimize the national standard of care. Therefore, we aimed to evaluate retrospectively the guideline-related 13-year data on breast cancer patients treated at our institution. PATIENTS AND METHODS: In a retrospective cohort study, the records of a total of 2,231 patients with primary breast cancer treated during the period of 1992-2005 at the Department of Obstetrics and Gynecology, University of Ulm, Germany, were analyzed. Based on the German national Step 3 (S3) guideline, a model was created to classify groups according to therapy 'conforming' and 'non-conforming' to guideline recommendations. RESULTS: In 2005, 70.2% of all patients included received both surgical and systemic adjuvant therapies conforming to the guideline. Guideline-conforming treatment was accompanied with significant advantages in terms of recurrence-free survival (RFS) and overall survival (OAS) rates. CONCLUSIONS: It has to be demanded that breast cancer patients are treated in conformity with the S3 guidelines. The reasons for a treatment not conforming to the guidelines should be analyzed for the detection of barrier factors, in order to optimize adherence to the guidelines and therefore to prolong RFS and OAS.

Regulated expression of the renin-angiotensin-system in human granulosa lutein cells: angiotensin II increases VEGF expression but its synthesis is reduced by hCG.

INTRODUCTION: The Renin-Angiotensin-System (RAS) has been suspected not only to control vascular tone but also to regulate angiogenesis. Angiotensin II has been shown to influence angiogenic factors such as vascular endothelial growth factor (VEGF). The Corpus luteum undergoes intense VEGF-dependent angiogenesis, regulated by luteinising hormone (LH) and human chorionic gonadotrophin (hCG). We therefore hypothesised, that locally produced Angiotensin II could act as a physiological co-regulator with hCG in luteal VEGF expression. MATERIALS AND METHODS: We investigated the expression of RAS components and their regulation by hCG in human granulosa lutein cells using RT-PCR, immunocytochemistry and Western blotting. In addition, we studied the effect of Angiotensin II on basal and hCG-stimulated VEGF expression using TaqMan-analysis, ELISA, and Western blot analysis. RESULTS: Human granulosa lutein cells express angiotensinogen and angiotensin converting enzyme (ACE) and synthesise Angiotensin. In addition, they express both Angiotensin receptors. Angiotensin II stimulated VEGF mRNA (p < 0.05) and protein expression (p < 0.05). However, hCG decreased angiotensinogen (p < 0.05) and Angiotensin II (p < 0.05). Both, the addition of Angiotensin II and its inhibition using Candesartan did not change the magnitude of hCG-increased VEGF expression. CONCLUSION: These findings suggest a role for locally synthesised Angiotensin II in the regulation of luteal VEGF expression. However, Angiotensin II does not appear to have a major contribution in the presence of hCG when the RAS pathway is down-regulated.

Ovarian metastasis of a lymphoma presenting as primary ovarian cancer.

BACKGROUND: Ovarian metastases are being found in a variety of different malignant diseases. CASE REPORT: A clinical case of a woman with a pelvic tumor and elevated CA125 levels, and suspected primary ovarian carcinoma is presented. Surgery revealed a metastasis of a B-cell non-Hodgkin's lymphoma. CONCLUSIONS: Literature research shows that elevated CA125 levels are often found in lymphomas.