Anxiety in caregiving partners of breast cancer patients.

PURPOSE: The aim of the present study was to determine the levels of anxiety of partners of breast cancer patients and to evaluate the differences of anxiety levels between patients and partners according to the stage of treatment, age and education level. METHODS: 57 spouses or domestic partners of breast cancer patients and 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based on stress-triggering procedures during breast cancer diagnosis and therapy. RESULTS: State anxiety levels of partners were highest in partners who accompanied their patients when presenting for examinations and operations and tumorboard decisions (Mean State-Scores 52, 45 and 46.5). Anxiety scores were lowest at the stage of ongoing chemotherapy or follow-up. The 25% quartile of partners with the highest state anxiety levels had a significantly higher educational level (p = 0.023). Young men aged 18-35 years showed the highest levels of both trait and state anxiety. Partners showed significantly higher levels of anxiety than the patients for anesthetic complications (p < 0.001), e.g., fear of not waking up from general anesthetic and postoperative pain (p < 0.001). Patients showed significantly higher levels of anxiety for hairloss (p < 0.001), weight gain during chemotherapy (p < 0.001) and postoperative scars (p = 0.027). CONCLUSION: Breast cancer patients are much more concerned about body image issues than their male partners. As these body image-associated concerns often arise from the fear of loosing attraction to their partner, these fears might be reduced by speaking about them openly. Partners are mostly concerned about surgery and anesthetic-related complications. Therefore, preoperative medical information to the partner is mandatory. Partners of breast cancer patients should be included in psycho-oncological support and medical briefings. Probably high anxiety levels of both partners and patients should be taken into account (due to younger age, lower educational level and procedures causing distress). These partners and patients should receive extra careful (clarification) counselling and (treatment support such as a psycho-oncologist) involvement of a psyco-oncologist.

Treatment anxiety in breast cancer patients.

INTRODUCTION: The aim of the present study was to determine and evaluate the levels of anxiety of breast cancer patients according to the state of treatment, age and education level, as well as the anxiety potential of certain procedures during breast cancer treatment. METHOD: 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based to stress triggering procedures during breast cancer therapy. The testing was accomplished with the Mann-Whitney U test, the significance level was set to 0.05. RESULTS: Patients who appeared for tumor board decision showed the highest state-anxiety levels (55.79 SD ± 18.73) followed by patients undergoing surgery (50.24 SD ± 13.84). Patients already undergoing chemotherapy had lower state-anxiety levels than the group of all other patients (p = 0.012). Women undergoing chemotherapy showed lower anxiety levels relating to many procedures of breast cancer treatment. The 25% quartile of patients with the highest levels in the trait score showed a significant poorer education level (p = 0.009). Age showed no statistical influence on the anxiety level of breast cancer patients.  CONCLUSION: Patients with probably high anxiety levels (younger age, low education level, and those appearing for frightening procedures) should receive extra careful clarification and treatment support such as a psycho-oncologist.

Fetal cephaloceles: prenatal diagnosis and course of pregnancy in 65 consecutive cases.

PURPOSE: To scrutinize the characteristics of all cases with antenatally established diagnosis of cephalocele in two tertiary referral centers. METHODS: We retrospectively reviewed 65 cases diagnosed with cephaloceles and tabulated sonographic findings and autopsy recordings as well as medical charts of all survivors in terms of clinical outcome. RESULTS: The case notes of 65 fetuses were available for final analysis. Gestational age (GA) at diagnosis ranged from 10.4 to 38.1 weeks. Of our cohort, 53/65 cases (80%) had occipital protrusions, 10 (15%) were found to have frontal lesions, and another two had parietal cephaloceles. A total of 52 pregnancies were terminated or resulted in intrauterine fetal demise (78%). In 18 cases (11%), the cephalocele was part of underlying syndromic disorders (e.g., Meckel-Gruber syndrome). Thirteen pregnancies were continued until term, out of which all affected individuals were live-born. Neurosurgical intervention was prompted within the first 7 months postnatally. CONCLUSIONS: In general, the outcome of fetuses with cephaloceles is rather poor as four out of five pregnancies were terminated. Postnatal outcome of all survivors in our cohort was rather determined by localization of the cele and more important by the presence and severity of concomitant malformations than the extent of the lesion.

Hybrid approach of retractor-based and conventional laparoscopy enabling minimally invasive hysterectomy in a morbidly obese patient: case report and review of the literature.

Minimally invasive hysterectomy in obese patients may be limited by laparoscopic sight on the one hand and by intraoperative complications related to reduced ventilation due to pneumoperitoneum on the other. Retractor-based laparoscopy offers an operative technique reducing anesthesia risks. We report the case of laparoscopic hysterectomy in an obese patient of short stature. Laparoscopic supracervical hysterectomy was performed by a hybrid approach of a retractor system exerting its effects on lifting the abdominal wall through gravity and conventional laparoscopy, thus bypassing the adverse effects of pneumoperitoneum on ventilation.

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

PURPOSE: Ewing'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. METHODS: We present a patient with primary vulvar Ewing's sarcoma with pulmonary metastasis who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck. RESULTS: The present report is the third case of a primary vulvar Ewing's 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. CONCLUSION: The 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 I: basic diagnostic and therapeutic principles and treatment of gynecological malignancies.

PURPOSE: Cancer 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. METHODS: This review focuses on general diagnostic and therapeutic principles including systemic therapy for malignancies in pregnancy. RESULTS: In part I, we report on diagnosis and therapy of gynecological tumors. CONCLUSION: The 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.

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

PURPOSE: To 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.

Does acetic acid influence the non-dysplastic Pap smear?

OBJECTIVE: Acetic 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. METHODS: Patients 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. RESULTS: In 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. CONCLUSIONS: The 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.

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

PURPOSE: In case of non-gynecological solid tumors and hematological malignancies diagnosed during pregnancy, individual diagnostic and treatment options must be established by an interdisciplinary team. METHODS: In part II of the present review we report on diagnostic and therapeutic principles in distinct entities of solid and hematological malignancies. RESULTS: On 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. CONCLUSIONS: The 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.

Arthrogryposis multiplex congenita and Pena-Shokeir phenotype: challenge of prenatal diagnosis--report of 21 cases, antenatal findings and review.

OBJECTIVE: To elaborate the antenatal sonographic findings of fetuses with the suspicion of fetal akinesia, thereby focusing on the accuracy of prenatal differentiation between subtypes of fetal akinesia, namely Pena-Shokeir phenotype (PSP) and arthrogryposis multiplex congenita (AMC). METHODS: We herein present our experience of 21 patients with PSP and AMC diagnosed antenatally at a tertiary prenatal referral center. During the study period 30,485 consecutive high- and low-risk pregnancies were examined. The prenatal sonograms, pediatric charts and autopsy data of affected individuals were reviewed. Our findings were analyzed together with findings retrieved from the literature. RESULTS: The diagnosis of AMC has been established between 12+0 and 30+1 gestational weeks, whereas cases found to have PSP were all diagnosed in advanced pregnancy. In accordance to previous findings, our data suggest that pulmonary hypoplasia is obligatory in PSP and cannot be found in AMC. Therefore, all pregnancies (9/9) affected by PSP were terminated on parental request. Of those fetuses with AMC, 3/12 were liveborn, 2 of which have neuromotoric disabilities. CONCLUSIONS: Establishing the correct prenatal diagnosis of PSP and AMC at an early stage and its diligent prognostic evaluation play a crucial role in order to provide adequate advice to the afflicted parents and to enable appropriate intervention at an early stage.

PSMD9 expression correlates with recurrence after radiotherapy in patients with cervical cancer.

In the current retrospective cohort study, the expression of the Proteasome 26S non-ATPase Subunit 9 (PSMD9) was investigated in 102 patients with cervical cancer. The rat homologue of PSMD9, Bridge-1, was identified as a binding protein of the transcription factors PDX-1 and E-12 via its PDZ-domain. The aim of the current study was to evaluate the prognostic or predictive value of PSMD9 expression as a biomarker for patients with cervical cancer. Tissue microarrays were constructed from formalin-fixed paraffin-embedded tissue specimens of cervical cancer and peritumoral stroma after hysterectomy and a Bridge-1 antibody was used to perform immunohistochemistry. The immunoreactions were analyzed using an immunoreactive score, which evaluated the number of positive cells as well as their intensity of PSMD9 expression. A misinterpretation of statistically significant results after multiple testing was controlled by the false discovery rate correction using the algorithm of Benjamini and Hochberg. All tumor tissues and almost all peritumoral stroma tissues expressed PSMD9. The PSMD9 expression in tumor tissues was significantly higher compared with the peritumoral stroma. PSMD9 expression correlated significantly with the expression of the proliferation marker MIB-1. Patients with stronger PSMD9 expression tended to exhibit a higher odds ratio for the recurrence of the disease in all patients (n=102) as well as in the subgroup of 47 patients having received a combined chemoradiotherapy following hysterectomy. In the group of 62 patients having that received radiotherapy following hysterectomy, which included the chemoradiotherapy patients, a higher PSMD9 expression significantly increased the odds for a recurrence to 1.983-fold even after FDR correction (P=0.0304). In conclusion, PSMD9 was indicated to be overexpressed in tumor tissues and associated with tumor cell proliferation. Therefore, PSMD9 may be useful as a tumor marker. Furthermore, increased PSMD9 overexpression may be used to predict resistance against radiation.

Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes.

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagen-like tail subunit gene (COLQ) cause synaptic basal-lamina associated CMS with end-plate AChE deficiency. Here we present the clinical and molecular genetic findings of 22 COLQ-mutant CMS patients, carrying a total of 20 different COLQ mutations, 11 of them had not previously been reported. Typically, patients with esterase deficiency suffer from a severe, progressive weakness with onset at birth or in early infancy. In addition, patients with a late onset showing a mild course of disease are described. AChE inhibitor therapy, beneficial for other forms of CMS, is of no effect in cases of esterase deficiency. The large cohort of COLQ patients studied here enabled us to define additional clinical presentations associated with COLQ mutations that differ from the 'classical' phenotypes: several patients with disease onset at birth or in early infancy presented an unexpected, mild disease course without significant progression of weakness. Moreover, many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness. There was no long-term objective benefit from esterase inhibitors treatment in COLQ patients. Surprisingly, a short-term beneficial effect was observed in four patients and a Tensilon test was positive in two. Treatment with ephedrine was efficient in all five cases where it was administered. The variability of phenotypes caused by COLQ mutations, the divergence from the previously published classical clinical features and an initial positive response to esterase inhibitors in some patients may obscure AChE deficiency as the molecular cause of the disease and delay the start of appropriate therapy. Moreover, overlap with other CMS subtypes and potentially absence of a repetitive compound muscle action potential should be considered in the diagnosis of COLQ-mutated patients.

Elaborations on Corallopyronin A as a Novel Treatment Strategy Against Genital Chlamydial Infections.

Ascending Chlamydia trachomatis infection causes functional damage to the fallopian tubes, which may lead to ectopic pregnancy and infertility in women. Treatment failures using the standard regimens of doxycycline and azithromycin have been observed. We tested the polyketide-derived α-pyrone antibiotic Corallopyronin A (CorA) that inhibits the bacterial DNA dependent RNA polymerase and has strong activity against various extracellular and some intracellular bacteria. Extensive testing in cell culture infection models and in an ex vivo human fallopian tube model under different oxygen concentrations was performed to assess the anti-chlamydial efficacy of CorA at physiological conditions. CorA showed high efficacy against C. trachomatis (MICN/H: 0.5 µg/mL for serovar D and L2), C. muridarum (MICN/H: 0.5 µg/mL), and C. pneumoniae (MICN/H: 1 µg/mL) under normoxic (N) and hypoxic (H) conditions. Recoverable inclusion forming units were significantly lower already at 0.25 µg/mL for all tested chlamydiae. CorA at a concentration of 1 µg/mL was also effective against already established C. trachomatis and C. pneumoniae infections (up to 24 h.p.i.) in epithelial cells, while efficacy against C. muridarum was limited to earlier time points. A preliminary study using a C. muridarum genital infection model revealed corresponding limitations in the efficacy. Importantly, in an ex vivo human fallopian tube model, the growth of C. trachomatis was significantly inhibited by CorA at concentrations of 1-2 µg/mL under normoxic and hypoxic conditions. The overall high efficacies of CorA against C. trachomatis in cell culture and an ex vivo human fallopian tube model under physiological oxygen concentrations qualifies this drug as a candidate that should be further investigated.

Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer Cell Lines.

BACKGROUND: Vitamin D is known for its anticancer potential. Prostaglandin E2 (PGE2) is a proliferative and inflammation-activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE2 metabolism was shown recently. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.

Microbiota-based analysis reveals specific bacterial traits and a novel strategy for the diagnosis of infectious infertility.

Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life.

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.

Management of Very Early-onset Fetal Growth Restriction: Results from 92 Consecutive Cases.

AIM: To evaluate management of early-onset intrauterine growth restriction (IUGR) and to define outcome according to obstetric setting. PATIENTS AND METHODS: During an 11-year period (2000-2011), data of patients presenting with IUGR and preterm delivery of less than 30 weeks of gestation at a tertiary perinatal center were retrospectively reviewed. RESULTS: A total of 92 pregnancies were investigated. Delivery was indicated for fetal reasons in 38 out of 92 patients. Sixteen children of our cohort died within one year post partum, out of which eight had suffered from severe early-onset IUGR causing iatrogenic preterm delivery. Concerning the fetal outcome, gestational age at delivery and antenatal exposure to corticosteroids were found to be crucial. CONCLUSION: In some cases, respiratory distress syndrome prophylaxis and a "wait and see" approach to management in favor of a prolongation of the pregnancy might be favorable. Randomized prospective trials in early-onset IUGR with threatened preterm deliveries are needed in order to define guidelines for an individually tailored management of early-onset preterm infants.

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.

Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on clinicopathological parameters.

The role of trefoil factor 3 (intestinal) (TFF3) has been analyzed in numerous cancers, such as breast and gastrointestinal cancer, and has been associated with poor prognosis. However, the role of TFF3 in ovarian cancers is not clear. Expression analysis of TFF3 in 91 ovarian cancer patients was performed by immunohistochemistry of primary paraffin-embedded tumor samples. The results were scored according to staining intensity and percentage of positive tumor cells resulting in an immune-reactive score (IRS) of 0-12. These results were correlated with clinicopathological characteristics and survival. TFF3 expression in our patient cohort exhibited a tendency towards improved overall and progression-free survival (PFS). In TFF3-positive serous and high-grade serous ovarian cancers, the median PFS was 27.6 months [95% confidence interval (CI): 0-55.7] vs. 15.2 months in TFF3-negative tumors (95% CI: 13.8-16.6) (P=0.183). The median overall survival was 53.9 months in TFF3-positive tumors (95% CI: Non-applicable) vs. 44.4 months in TFF3-negative cases (95% CI: 30.5-58.3) (P=0.36). TFF3 negativity was significantly associated with higher tumor grade (P=0.05). Based on our results, further studies are required in order to elucidate whether survival and chemosensitivity are affected by TFF3 expression in ovarian cancer.