Biomedical subjects
Publications and source records attributed to R Kimmig.
MRI has proved beneficial in characterizing ovarian masses that are indeterminate by sonographic criteria. MRI can distinguish between benign and malignant ovarian tumors with high sensitivity and specificity and is capable of characterizing many adnexal masses. MRI should be therefore included in the preoperative diagnostic of adnexal masses.
The treatment of breast cancer is changing continually. Thus, sentinel lymph node dissection is considered today as standard in the therapy of small unifocal breast carcinoma with clinically negative axillary lymph nodes. Concerning adjuvant therapy, the 9th Early Adjuvant Breast Cancer Meeting, along with a consensus conference, took place in Saint Gall on January 26-29, 2005. The publication of the corresponding congress report is expected for early summer of 2005.
The continuing increase in teenage pregnancies and abortions calls for more effective sex education on the one hand, including a detailed explication of the (perfectly normal) changes an adolescent body is undergoing, but we also need to understand the way teenagers actually do use contraceptives. Modern contraception for teenagers should not cause any side effects and its efficacy must not be linked to compliance. Gynaecologists must acquaint themselves with the laws covering the prescription of contraceptives to adolescents. Whether hormonal contraceptives for men are also suitable for teenage boys remains to be seen. Advising mentally or physically handicapped teen-agers or those with chronic diseases on their contraceptive options is particularly challenging. Adolescents are more prone to contract HPV infections and thus need to be screened, counselled and told about the association between HPV and cervical dysplasia.
PURPOSE: To determine the value of magnetic resonance imaging (MRI) of the pelvis in the preoperative diagnosis of endometriosis. MATERIALS AND METHODS: Over a period of 8 months, preoperative MRI of the pelvis were obtained in 13 patients with suspected endometriosis (mean patient age 34.6 years; range 25 - 47 years). RESULTS: In 9 of 13 patients (69 %), the diagnosis of endometriosis was made by MRI and confirmed by laparoscopy in 8 cases. In 2 of 13 patients, endometriotic lesions were detectable by laparoscopy only. In the remaining 2 patients, no endometriosis was visible on MRI or by laparoscopy. MRI was able to visualize a total of 19 endometriotic lesions, with 14 (74 %) confirmed by histopathologic examination following laparoscopy. Five of these 19 lesions (26 %) visible on MRI were not seen by laparoscopy. Using laparoscopy and subsequent histopathologic examination, 27 endometriotic lesions were diagnosed, with 13 (48 %) not seen on the preoperative MRI. CONCLUSION: MRI and laparoscopy are complementary diagnostic tools that will best document the full extent of endometriosis when combined. MRI can visualize additional lesions inaccessible to laparoscopy. Thus, MRI of the pelvis should used preoperatively for surgical treatment planning.
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The occurrence of malignancies during pregnancy has increased over the last decades. They complicate approximately 1 per 1000 pregnancies. The most common malignancies associated with pregnancy include malignant melanoma, malignant lymphomas and leukemia, and cancer of the cervix, breast, ovary, colon and thyroid. Since it is impossible for prospective randomized clinical trials to be conducted in this field, relevant data have been generated from case reports and matched historical cohort studies in order to evaluate the treatment outcomes and the issues complicating the management of malignancy in the pregnant patient. There is almost always a conflict between optimal maternal therapy and fetal well-being. The maternal interest is for an immediate treatment of the recently diagnosed tumor. However, the optimal therapy, be it chemotherapy, radiotherapy or surgery, may impose great risks on the fetus. Consequently, either maternal or fetal health, or both, will be compromised. Therefore, both the pregnant patient and her physician are often in a dilemma as to the optimal course. On the basis of the medical facts, we discuss the issues raising potential ethical conflicts and present a practical ethical approach which may help to increase clarity in maternal-fetal conflicts. We review the available data informing the incidence and impact of the most common malignancies during pregnancy and their treatment on both the pregnant woman and her fetus. The optimal therapy for the tragic diagnosis of cancer in pregnancy requires a collaborative and interdisciplinary approach between gynecologists, oncologists, obstetricians, surgeons, neonatologists, psychologists, nursing staff and other disciplines. The purpose of this article is not to answer specific questions or to construct management schemes for specific tumors but to provide a framework for approaching some of these complex issues.
Although ovarian cancer treatment has advanced in the last 20 years, long-term survival remains stable. The purpose of this study was to determine whether survival has improved in line with treatment advances in a population-based prospective cohort of ovarian cancer patients (1978-1997, with a follow-up through to 2000). The 10-year overall survival rate for cancer patients was similar before and after 1988: 32.2% (n=1661) and 34.4% (n=2089). For patients after 1988, a 12-month prolongation of median survival was observed. In terms of stage according to the International Federation of Gynecology and Obstetrics (FIGO), only FIGO I and FIGO II patients showed, in addition to a prolongation in survival, an absolute improvement of 12.9 and 12.6% after 5 years and of 13.2 and 8.6% after 10 years. This hardly affected the survival of the total sample. For the most frequent stage FIGO III patients and for FIGO IV patients, a prolongation in survival time, but no improvement in survival rate, was seen after five or 10 years. The progress in FIGO I and II patients may be due to more accurate staging. More effective chemotherapy may also explain some of the improvement. The prolongation in FIGO-stages III-IV may be due to more radical surgery. Patient selection criteria, not only the treatment modalities, may be responsible for the superior results reported in clinical trials. Cancer registries are important for evaluating the quality of healthcare delivery.
OBJECTIVE: To report a prospective phase II study of patients with disseminated peritoneal carcinomatosis and symptomatic disease, in whom the peritoneal metastases were resected. PATIENTS AND METHODS: From 1995 to 1999, 32 patients (20 men and 12 women, median age 56 years, range 32-75) with peritoneal carcinomatosis were enrolled in the trial. Pain and ascites were determined according to the National Cancer Institute score/criteria, and performance scored according to the World Health Organisation criteria. RESULTS: All patients had intraperitoneal disseminated malignancies with clinically evident ascites, and presented with abdominal pain. The median (range) operative duration was 2.9 (1-5.5) h and the hospital stay 25 (10-44) days, with no deaths at 30 days. The ascites was completely cured in 25 of the 32 patients, pain relieved in 28 and the performance score improved in 25. The median survival time was 1 year; the 1- and 2-year survival rates were 45% and 38%, respectively. Patients with residual metastases after incomplete resection had a significantly worse prognosis, but the prognosis was significantly better in those with a low tumour burden. CONCLUSIONS: Peritoneal carcinomatosis is treatable; radical peritonectomy improves the performance score in selected patients with cancer-related ascites and/or pain, and is now the standard approach in the authors' Cancer Centre.
BACKGROUND: Despite the progress that has been achieved in the last years, recurrence rates in ovarian cancer patients are still considerably high and the majority of patients ultimately become candidates for second-line treatment. Carboplatin reinduction is a broadly adopted regimen in patients with recurrences occurring six months or later after first-line treatment. Gemcitabine is among the candidates as combination partner in second-line regimens. PATIENTS AND METHODS: We performed a study with escalating doses of gemcitabine combined with carboplatin in 26 platinum-pretreated patients with recurrent ovarian cancer and a treatment-free interval of 6+ months. Dose-limiting toxicity (DLT) and a maximum tolerable dose (MTD) recommendable for further trials was evaluated. RESULTS: The DLT was myelosuppression, mainly thrombocytopenia. No dose limiting non-hematological toxicities were observed. The MTD of gemcitabine was 1,000 mg/m2 given on days 1 + 8 of a three-week schedule combined with carboplatin AUC 4 given on day 1. The majority of evaluable patients showed an objective response (62.5%), and median progression-free and overall survival were 10 and 18+ months, respectively. CONCLUSION: Gemcitabine-carboplatin given according to the MTD is well tolerated and active against recurrent platinum-sensitive disease. A randomized trial comparing carboplatin with or without gemcitabine in platinum-sensitive ovarian cancer has already been initiated.
Endometrial carcinoma is the most common gynecologic malignancy in perimenopausal and postmenopausal women. A role of mismatch repair genes, like hMLH1 and hMSH2 in their pathogenesis, has been suggested. Loss of their function leads to the accumulation of replication errors (mutator phenotype), which are responsible for further mutations in genes with microsatellite sequences in their coding region, such as Bax. We analyzed the expression of hMLH1, hMSH2, and Bax genes in 89 formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were scored with regard to percentage of positive tumor cells (0%, <10%, 10 to 50%, >50%), and relative staining intensity (1+, 2+, 3+). The staining results were correlated with clinicopathologic features and survival. Loss of hMSH2 expression (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was seen in 12.4% (11/89) of the cases, particularly in endometrioid tumors with mucinous differentation (5/11; 45%; P =.03). No significant association was found between the immunoscores and grade, stage criteria of the International Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11 tumors with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11; 36.4%; P =.017). In multivariate analysis (Cox model), significantly longer survival was found for patients with tumors in FIGO Stage I-II (P <.0001), endometrioid type (P =.001), low grade (P =.001), and absence of hMLH1 expression (P =.027). Our results suggest that loss of function of hMLH1 and Bax occur in a subgroup of endometrial carcinoma. In addition to the classical prognostic factors, absence of hMLH1 expression is associated with better outcome of patients.
Paravaginal abscess in pregnancy. We report the diagnosis and treatment of an infected Gartner's duct cyst during pregnancy. The patient presented with lower abdominal pain, fever (38.5 degrees C) and an elevated C-reactive Protein level. Pelvic examination revealed a painful paravaginal mass. Sonography was not able to detect the cranial border of the tumor. Magnetic resonance imaging (MRI) revealed fluid accumulation laterodorsal to the vagina without evidence of a connection with the retroperitoneal space. An infected Gartner's duct cyst with consecutive abscess formation along the mesonephric duct system, was diagnosed. Following transvaginal drainage, the remainder of the pregnancy was uneventful and the patient was delivered vaginally at 40 + 5 weeks without complications. - The rare clinical finding of a paravaginal abscess in pregnancy was treated without termination of the pregnancy. Preoperative planning of the surgical approach using MRI can be easier for pelvic processes extending out of the pelvis than using ultrasound and is less painful for the patient.
Deregulation of proliferation and apoptosis is known to contribute to neoplastic transformation and growth. Using specific antibodies for the cellular apoptosis susceptibility (CAS) gene, caspase-3, Bcl-2, and Bax, we examined the protein expression in 89 endometrial carcinomas and in 56 samples of nonneoplastic adjacent endometrium for comparison. Immunostaining results were scored with regard to approximate percentage of positive tumor cells (< 10%, 10% to 50%, > 50%) and relative immunostaining intensity (1+, 2+, 3+). In nonneoplastic endometrium, CAS protein was expressed in 70.6%, Bax in 64%, caspase-3 in 52%, and Bcl-2 in 87%. In neoplastic tissue, CAS was present in 93% of the tumors, Bax in 88%, caspase-3 in 77%, and Bcl-2 in 51%. Bcl-2:Bax ratio was > 1 in 9 cases (10%). In cases of atrophy (n = 24) and simple (n = 10) and complex (n = 22) hyperplasia in the adjacent endometrium, lower levels of expression compared with carcinoma were observed for CAS (p = 0.003), caspase-3 (p = 0.034), and Bax (p = 0.04) and higher levels for Bcl-2, although for this protein the results were not statistically significant (p = 0.32). There was no association between immunoscores and FIGO stage. High caspase-3 levels were seen in endometrioid tumor type (p = 0.017). CAS expression was higher in grade 3 tumors (p = 0.002) and older patients (p = 0.013). All tumors of younger patients (< 50 years) were Bcl-2 negative (p = 0.037). Caspase-3 correlated positively with CAS (p = 0.008), Bax (p = 0.04), and low Bcl-2:Bax ratio (p = 0.043), and inversely (as a trend) with Bcl-2 (p = 0.056). Survival analysis (Kaplan-Meier and Cox regression) established a strong association between prognosis and stage, grade, and histologic type (all p < or = 0.0036). In addition, shorter survival was observed for patients whose tumors contained > 50% of positive cells for caspase-3 (p = 0.024) or for CAS (p = 0.04). Age, Bcl-2, Bax, and Bcl-2:Bax ratio did not provide prognostic information. Our results suggest a role of CAS, Bcl-2, Bax, and caspase-3, which are apparently involved in the progressive deregulation of proliferation and apoptosis leading from simple and complex hyperplasia to carcinoma. In addition, CAS and caspase-3 protein levels may be useful markers in predicting the outcome of the patients.
Flow cytometric assessment of DNA-ploidy and S-phase fraction in malignant tumors is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g., tumor, stromal and inflammatory cells. To evaluate the effect on quality of DNA cell cycle analysis and determination of DNA ploidy, cytokeratin labeling of epithelial cells was used for tumor cell enrichment in breast, ovarian, cervical and endometrial cancer prior to DNA analysis. In a prospective study, tumor cell subpopulations of 620 malignant tumors were labeled by a FITC-conjugated cytokeratin antibody (CK 5, 6, CK18 and CK 5, 6, 8 and CK 17, respectively) prior to flow cytometric cell cycle analysis. Compared to total cell analysis, detection rate of DNA-aneuploid tumors following cytokeratin labeling was increased from 62% to 76.5% in breast cancer, from 68% to 77% in ovarian cancer, from 60% to 80% in cervical cancer and from 30% to 53% in endometrial cancer. Predominantly in DNA-diploid tumors, a significantly improved detection of S-phase fraction of the tumor cells was shown due to the elimination of contaminating nonproliferating "normal cells". S-phase fraction following tumor cell enrichment was increased by 10% (mean) following cytokeratin staining in ovarian and endometrial cancer, by 30% in breast cancer and even by 70% in cervical cancer compared to total cell analysis. Thus, diagnostic accuracy of DNA-analysis was enhanced by cytokeratin labeling of tumor cells for all tumor entities investigated.
PURPOSE: Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, have been shown to be related to poor prognosis in a variety of malignant solid tumors. Studies on the prognostic relevance of uPA and PAI-1 in ovarian cancer, however, have been inconclusive. The current study tests the hypothesis that elevated expression of uPA and PAI-1 is associated with prognosis and disease progression. EXPERIMENTAL DESIGN: uPA and PAI-1 were prospectively measured by quantitative ELISA in tumor samples from 103 ovarian cancer patients (82 primary invasive epithelial carcinomas, 9 low malignant potential tumors, and 12 recurrent ovarian carcinomas). RESULTS: uPA but not PAI-1 levels were consistently associated with malignant progression, with levels increased from low malignant potential tumors to primary tumors (uPA, P = 0.04; PAI-1, P = 0.019), from early to advanced disease stages (uPA, P = 0.014; PAI-1, P = 0.23), and from primary to intra-abdominal metastatic tumors (uPA, P = 0.001; PAI-1, P = 0.16). High uPA and PAI-1 levels were associated with residual tumor volumes of >1 cm (P = 0.001 and P = 0.016, respectively). Among invasive International Federation of Gynecologists and Obstetrician stages I-IV tumors, elevated levels of uPA (>5.5 ng/mg) and PAI-I (>18.8 ng/ml) were associated with a shortened progression-free survival (uPA, P = 0.003; PAI-1, P = 0.039) and overall survival (uPA, P = 0.0002; PAI-1, P = 0.007). In multivariate analysis, uPA retained prognostic independence for progression-free survival (P = 0.037) and overall survival (P = 0.006). CONCLUSIONS: These data suggest that the uPA/PAI-1 axis may play an important role in the intra-abdominal spread and reimplantation of ovarian cancer cells. The prognostic relevance of uPA and PAI-1 supports their possible role in the malignant progression of ovarian cancer.
OBJECTIVE: This study was performed to evaluate the effectiveness and side effects of loop electrosurgical excision procedure (LEEP) in comparison to cold knife conization for the treatment of cervical intraepithelial neoplasia (CIN). MATERIAL AND METHODS: Between January 1996 and July 1998, 177 patients underwent conization. In a matched-pair setting, 50 cases with LEEP were compared with 100 classical conization cases. LEEP was performed with ectocervical and endocervical excision. RESULTS: Perioperative complications were less in the LEEP group (6% vs. 11%). The mean volume of LEEP specimens (1.6 cm3) was significantly smaller than the volume of cone specimens (2.6 cm3). Thermal artifacts were negligible. There were no significant differences in the proportion of margin involvement (20% vs. 19%) and residual/recurrent CIN. The endocervical excision contained dysplastic tissue in 38% of the cases; more important, a positive endocervical excision was found in 14/21 CIN 3 cases (67%). The success rate, was similar in both groups (96% vs. 97%). Hospitalization time was less for the LEEP group. CONCLUSIONS: LEEP conization is a safe and cost effective procedure with a lower complication rate providing a significantly smaller specimen compared to cold knife conization. Therefore, LEEP conization may substitute cold knife conization. However, we do recommend to perform LEEP conization with an endocervical excision to reduce residual CIN.
BACKGROUND: Reports of obstetric complications of mothers infected with hepatitis C virus (HCV) are limited and the risk of mother-to-infant transmission varies widely. We assessed the course of pregnancy in HCV-infected women and the rate of vertical transmission. METHODS: Between October 1992 and December 1996, 3712 pregnant patients of the university hospital Grosshadern Munich, Germany, were screened for anti-HCV and analyzed for HCV-RNA by polymerase chain reaction. Clinical and biochemical parameters were monitored. Children born to HCV-positive women were followed up at 6, 12 and 18 month intervals and screened for anti-HCV and HCV-RNA. RESULTS: Thirteen (42%) of 31 anti-HCV positive patients had a cesarean section which was twice the rate of that in the HCV-negative group (p=0.004). None of the cesarean deliveries was due to complications directly caused by HCV infection. Nine (29%) of 31 anti-HCV positive women had preterm delivery compared to 19% in the anti-HCV negative patients, the difference being statistically not significant. Fetal outcome parameters such as APGAR score, umbilical pH and birth weight of HCV infected pregnancies were not impaired. All 29 babies tested for anti-HCV were seropositive after birth. Between 12 and 18 months of age, 10% of the infants still were anti-HCV positive, whereas only one baby was HCV-RNA positive beyond 12 months yielding a vertical transmission rate of 5% among HCV-RNA positive mothers. CONCLUSION: Anti-HCV positive pregnancies have an increased risk of cesarean delivery, probably due to the high-risk collective of anti-HCV positive mothers. The mother-to-child transmission rate is low and linked to maternal HCV-RNA positivity.
We evaluated self-collected vaginal human papillomavirus tests for cervical cancer screening and compared it with the specimens taken directly from the cervix in 247 patients at high-risk for cervical disease. The sample taken by the patient showed human papillomavirus DNA in a higher percentage than the sample taken by a doctor. Sensitivity of high-risk human papillomavirus types for high-grade cervical precursors (CIN 2/3) and invasive cervical cancers were 93% for both methods.
Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.