Friederike Hoellen

Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients.

Ovarian carcinomas are associated with increased inflammation which is based upon an up-regulation of inducible cyclooxygenase-2 (COX-2). Moreover, based on our previous published data, the extra-renal vitamin D metabolism seems to be dysregulated in comparison to healthy tissue. In order to gain further insight into the prostaglandin (PG)- and vitamin D-metabolism in ovarian carcinomas, the study aimed to evaluate the expression of the PG metabolising enzymes COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) compared to the vitamin D receptor (VDR) in benign and malignant ovarian tissues. Additionally, we determined the 25-hydroxycholecalciferol (25(OH2)D3) serum levels. Expression of VDR, COX-2 and 15-PGDH was determined by Western blot analysis. Serum levels of 25(OH2)D3 and PGE2 were measured by chemiluminescence-based and colorimetric immunoassay. We detected significantly higher expressions of the PG metabolising enzymes 15-PGDH and COX-2 in malignant tissue and PGE2 serum levels were 2-fold higher in tumour patients. Furthermore, we found an inverse correlation to the VDR-expression which was 62.1% lower in malignant tissues compared to that in benign tissues. Surprisingly, we could not detect any differences between the 25(OH2)D3 serum levels in either group (n=20). These data suggest a correlation between PG- and vitamin D-metabolism in ovarian carcinomas.

Spontaneous uterine rupture at the 21st week of gestation caused by placenta percreta.

AbstractPurposeTo describe the management of a ruptured uterus caused by placenta percreta in the 21st week of gestation.Methods We present a case report of a 33-year-old patient with a ruptured uterus in the 21st week of gestation who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck. Therapeutic management was performed by laparoscopy, and consecutive laparotomy and hysterectomy.Results A 33-year-old patient presented with severe abdominal pain in the 21st week of gestation at the department of abdominal surgery. A laparoscopy was performed to exclude appendicitis. There was about one liter of blood in the peritoneal cavity and a small, bleeding lesion in the fundus uteri was found which was coagulated. The blood was evacuated and the patient returned to department of gynecology. One hour after the first operation, the patient developed signs of hypovolemic shock and ultrasound showed absent fetal heart beat. An immediate laparotomy was performed and a ruptured uterus was detected. The fetus was removed and a hysterectomy performed. Pathology results showed a placenta percreta. After a few days in hospital and transfusion of 4 liters of blood the patient was discharged in a healthy condition.Conclusions In a pregnant woman with severe abdominal pain even in the 21st week of gestation a placenta percreta has to be considered as a differential diagnosis. If there is no evidence of other causes, laparoscopy may help to confirm the diagnosis and hysterectomy is a life saving intervention.

Cancer in pregnancy. Part I: basic diagnostic and therapeutic principles and treatment of gynecological malignancies

PurposeCancer in pregnancy is a rare circumstance. However, the coincidence of pregnancy and malignancy is supposed to increase due to a general tendency of postponing childbearing to older age. To date, clinical guidelines are scarce and experience regarding therapeutic management is limited to case reports.MethodsThis review focuses on general diagnostic and therapeutic principles including systemic therapy for malignancies in pregnancy.ResultsIn part I, we report on diagnosis and therapy of gynecological tumors.ConclusionThe diagnosis of gestational cancer faces both oncologist and obstetrician to the dilemma of applying appropriate diagnostic techniques and adequate local and systemic therapy to an expectant mother without harming the fetus.

Primary metastasized extraskeletal Ewing sarcoma of the vulva: report of a case and review of the literature

PurposeEwing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET) are closely related malignant neoplasms, usually affecting the skeletal system. Extraosseous ES/PNETs are uncommon, with occasional reports of tumors affecting the genitourinary tract. Only few cases of primary vulvar Ewing’s sarcoma/PNET have previously been reported.MethodsWe present a patient with primary vulvar Ewings sarcoma with pulmonary metastasis who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck.ResultsThe present report is the third case of a primary vulvar Ewings sarcoma and the first constellation with pulmonary metastasis at diagnosis in the current literature. We present the diagnostic and therapeutic management including surgery, chemotherapy and radiation.ConclusionThe treatment of the Ewing’s sarcomas and PNETs requires a multidisciplinary systemic approach. Despite its rarity, the differential diagnosis of vulvar sarcoma must be considered in young women.

Cancer in pregnancy. Part II: treatment options of breast and other non-gynecological malignancies

PurposeIn case of non-gynecological solid tumors and hematological malignancies diagnosed during pregnancy, individual diagnostic and treatment options must be established by an interdisciplinary team.MethodsIn part II of the present review we report on diagnostic and therapeutic principles in distinct entities of solid and hematological malignancies.ResultsOn the basis of a review of the current literature, clinical guidelines and algorithms have been established for diagnosis and therapy of maternal cancer during pregnancy.ConclusionsThe prognosis of the malignancy and the patient’s informed consent must be taken into consideration when the well-being of the expectant mother is weighed against the well-being of the unborn child in case of maternal cancer during pregnancy.

Expression of cyclooxygenase-2 in cervical cancer is associated with lymphovascular invasion

Cyclooxygenase-2 (COX-2) is associated with carcinogenesis and tumor progression. The current study analyzed the effect of COX-2 expression in patients with invasive squamous cervical cancer. Tissue samples from 123 cervical cancer patients were collected for a retrospective analysis using immunohistochemistry (IHC) with an antibody against COX-2. The clinical and survival data of the patients were analyzed. Positive staining for COX-2 (defined as an immunoreactivity score of ≥4) was detected in 28 patients (23%), with significantly higher percentages of staining in tumor cells compared with peritumoral stroma cells (P<0.001). COX-2 expression was significantly associated with lymphovascular space invasion (LVSI; P=0.017). The association of COX-2 expression with LVSI suggests a possible effect of COX-2 on tumor progression in cervical cancer. Further studies including larger patient collectives are required in order to perform analyses of clinical subgroups and patient survival.

Zervixkarzinom in der Schwangerschaft

ZusammenfassungDas Zervixkarzinom ist das zweithäufigste in der Schwangerschaft diagnostizierte Karzinom. Während das invasive Zervixkarzinom in graviditate selten ist, sind auffällige PAP-Abstriche und Krebsvorstufen in der Schwangerschaft in der Praxis ein häufiges Problem. Der vorliegende Beitrag erläutert die praktische Vorgehensweise bei suspekter Zervixzytologie in der Schwangerschaft. Darüber hinaus werden Stadien- und Gestationsalter-abhängige Therapieoptionen beim invasiven Zervixkarzinom in der Schwangerschaft unter Rücksichtnahme auf den Erhalt der Schwangerschaft aufgezeigt.AbstractCarcinoma of the cervix uteri is the second most diagnosed cancer during pregnancy. Although gestational cervical cancer is rare abnormal PAP smears and preinvasive lesions are frequently found during pregnancy. The present article depicts a practical approach to preinvasive cervical lesions during pregnancy. Furthermore, therapeutic options in cases of invasive cervical carcinoma diagnosed during pregnancy are presented according to the gestational stage and cancer stage, taking into account pregnancy preservation.

Does acetic acid influence the non-dysplastic Pap smear?

ObjectiveAcetic acid tests are commonly performed for colposcopic evaluation of the cervix. However, it is unclear whether the acetic acid influences normal Papanicolaou (Pap) smear results.MethodsPatients were routinely seen in our outpatient department between April and May 2009. Two Pap smears were performed in 50 patients. One smear was done before, the other after the acetic acid test. The smears were evaluated by an experienced cytologist. He did not know whether the smear was done with or without acetic acid.ResultsIn a normal smear, there was no influence of acetic acid on the cytologic result. In two patients, a smear of Pap III [Bethesda, atypical squamous cells of undetermined significance (ASCUS)] was seen before acetic acid test. This changed to Pap IIID [Bethesda, low-grade squamous epithelial lesions (LSIL)] after acetic acid test.ConclusionsThe acetic acid test does not seem to alter the result of the non-dysplastic smear. In contrast to this, a dysplastic smear seems to be influenced by the acetic acid. This should be evaluated in a further investigation.

Claudin‑1 expression in cervical cancer

Claudin-1 is a tight junction protein that has been demonstrated to be involved in tumorigenesis and tumor progression in various types of solid tumors. In the present study, the protein expression of claudin-1 in squamous cervical cancer tissues obtained from 106 patients was analyzed by immunohistochemistry. In addition, the grade of claudin-1 expression was analyzed for associations with certain clinicopathological parameters. A significant overexpression of claudin-1 was detected in the tumor cells, when compared with that in the peritumoral stroma. There was no significant association between claudin-1 expression and FIGO stage, tumor size, grading or the appearance of distant metastases. Cervical cancer patients scoring positive for claudin-1 protein expression tended to exhibit more lymph node metastasis (28.3%), compared with claudin-1-negative patients (7.1%). Regarding overall survival, the results of the present study suggest a better prognosis for claudin-1-negative patients. In order to elucidate whether claudin-1 overexpression has a significant prognostic impact on squamous cervical cancer, further studies are required.

Der Resektionsrand und seine Beurteilung

ZusammenfassungIn den letzten Jahren wurde eine intensive Diskussion um die Definition des freien Resektionsrandes geführt. Trotz der Wirkung von Strahlen- und Systemtherapie ist ein positiver Resektionsrand bei der brusterhaltenden und der ablativen Operation des Mammakarzinoms nach wie vor mit einer erhöhten Lokalrezidivrate assoziiert. Ein durch den Pathologen bestätigter positiver Resektionsrand führt daher zu Folgeoperationen, die für die Patientin in vielerlei Hinsicht belastend sind und die nachfolgende adjuvante Therapie verzögern können. Das Gebiet der intraoperativen Resektionsrandmessung wird intensiv beforscht, zahlreiche Methoden und Technologien wurden entwickelt, um den Brustoperateur zu unterstützen. Manche, wie Schnellschnittdiagnostik, Imprintzytologie, Ultraschall und Radiofrequenzspektroskopie, sind bereits in der klinischen Routine etabliert. Andere, wie Nahinfrarotbildgebung, Röntgendiffraktion, Hochfrequenzultraschall und Mikro-Computertomographie sind noch experimentell. In diesem Beitrag wird der aktuelle Stand der Definition eines freien Resektionsrandes behandelt und versucht, einen Überblick über die Techniken zur intraoperativen Resektionsrandbeurteilung zu geben.AbstractIn recent years there has been an intensive discussion about how to define a negative surgical resection margin. Despite the impact of radiation and systemic therapy a positive margin in breast surgery is associated with an increased risk of local recurrence. Thus, a positive margin confirmed by the pathologist results in further surgery that is troublesome for the patient in several ways and can also delay the initiation of adjuvant treatment. Therefore, the field of intraoperative margin assessment was intensively investigated and methods and technologies have been developed to support the breast surgeon in the operating theater. Some of these developments, such as frozen sections, touch imprint cytology, intraoperative ultrasound and radiofrequency spectroscopy are now established in the clinical routine. Others, such as near-infrared optical imaging, X-ray diffraction, high-frequency ultrasound and micro-computed tomography (CT) are still in the experimental stage. This article illustrates the current status of defining a negative surgical margin and gives an overview of the various and innovative technologies for intraoperative margin assessment.