Loss of p16 INK4 expression in invasive squamous cell carcinoma of the uterine cervix is an adverse prognostic marker.
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Biomarkers, Tumor↗
Biomedical subjects
L C Horn
Publications and source records attributed to L C Horn.
Occult tumor cells in pelvic lymph nodes and parametrial tissue of small-sized FIGO IB1 squamous cell carcinomas of the uterine cervix--results of a pilot study.
Micrometastases (MM) and occult tumor cell deposits (OTCD) in pelvic tissue may cause recurrences, and immunohistochemistry may improve their detection. We used cytokeratine-immunohistochemistry to investigate 263 pelvic lymph nodes and parametrial tissue for MM and OTCD obtained from eight squamous cell carcinomas (maximum tumor size: 2.5 cm). These patients were treated with radical abdominal hysterectomy (Piver type III) with complete tumor resection without receiving any adjuvant therapy. The mean count of resected pelvic lymph nodes was 32.9 (range 24-47). All lymph nodes were completely embedded, and three step sections were performed for routine histopathologic evaluation. Three patients developed pelvic side wall and five central tumor recurrences within a median time of 25.9 (range 8-55) months. On immunohistochemistry, only one case (12.5%) showed OTCD in a venule in the parametrial tissue. In patients with small cervical carcinomas (< 2.5 cm in largest dimension), OTCD can only rarely be detected by immunohistochemistry after careful handling of resected lymph nodes using step sectioning for routine histologic examination and complete processing of parametrial pelvic tissue. Therefore, tumor recurrence in those patients appears to be due to occult residual tumor cells that were not resected during the classical Wertheim-Meigs-procedure or that were disseminated during the surgical procedure and persisted in situ.
Adult↗
Another case of autosomal dominant exstrophy of the bladder.
OBJECTIVE: Exstrophy of the bladder is a rare malformation due to an anterior midline defect. Most cases of this condition with variable expression occur sporadically, but there are some cases indicative of a strong genetic component apart from environmental factors. This is a report about another rare mother-child pair with bladder exstrophy. METHODS: We present the clinical data of a familial case of bladder exstrophy with an affected mother and her equally affected male fetus. RESULTS: Prenatal diagnosis of bladder exstrophy in the fetus was assessed by ultrasound at the 19th gestational week and was confirmed after termination of pregnancy at the 21st gestational week. CONCLUSION: The present case may be additional evidence for an autosomal dominant inherited variant of this malformation complex with implication for counselling of affected patients.
Abortion, Induced↗
[MR-guided preoperative localization and percutaneous core biopsy of suspected breast lesions. Possibilities and experience on the vertically open 0.5-T-system].
PURPOSE: To evaluate the feasibility of performing breast interventions in a vertically open 0.5 T MR system (SIGNA SP/i, GE Medical Systems). To develop fitted equipment and to establish preoperative wire localization and percutaneous breast core biopsy as clinical routine procedures. PATIENTS AND METHODS: Initially, we applied a localization method with the patient placed in a sitting position in 31 cases using a single loop coil and a self-developed fixation device. Subsequently, 46 wire localizations and 28 percutaneous core biopsies were carried out in prone patient position using an open breast coil with an integrated biopsy device. The used instruments were either MR-compatible (18 G biopsy needle and localization wire, 14 G coaxial needle, prototype of a 16 G double-shoot gun) or MR-safe (double-shoot gun with 16 G needle). RESULTS: After biopsy we found the needle tip (18 G for a wire localization and 14 G for a percutaneous core biopsy, respectively) placed either within or close to the lesions (< 10 mm distance) for all patients. Out of a total of 66 benign lesions and 39 malignant tumors we missed the lesion (12 mm mean diameter, 4-25 mm range) during open biopsy in two cases and obtained a false negative result for one percutaneous biopsy of a 5 mm lesion. CONCLUSION: Preoperative wire localization and percutaneous core biopsy of suspicious breast lesions demonstrated by MRI can be carried out a vertically open 0.5 T MR scanner. The degree of accuracy is comparable with that of X-ray or ultrasound-guided procedures. A follow-up has to be performed in cases with a negative biopsy.
Adult↗
[Recommendations for the oncologic pathology report and morphologic factors associated with prognosis in endometrial carcinoma].
Summary. The endometrial carcinoma (EC) is the fourth common malignant tumor in women with a reported incidence for Germany of 24.5. The prognostic evaluation shows an overall five-year survival of more than 76 %. The histopathologic report should include the tumor type in detail with special consideration of serous-papillary, clear cell and endometrioid type. Stage T2 a and T2 b should only be diagnosed with clear-cut invasion of endocervical glands or the cervical stroma. In most cases of positive endocervical curetting, endmotrial carcinoma has been dislocated during fractional curetting and represents no indication for advanced surgery (Wertheim-Meigs-procedure). Special reference should be made on isthmic carcinoma, because there is a combination of lymphatic drainage of the cervix and corpus uteri. Well established prognostic factors are surgical tumor stage (pTNM-system), pelvic lymph node metastases and tumor grading. Molecular biologic and cellkinetic parameters should be used for research purpose only.
Endometrial Neoplasms↗
[Endometrial carcinoma - molecular pathogenesis meets histomorphology and treatment].
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Cell Transformation, Neoplastic↗
[Precancerous lesion of the endometrium and endometrial morphology in patients with tamoxifen therapy].
The endometrioid type of endometrial adenocarcinoma,(type 1-carcinoma) is estrogen-dependent and frequently associated with endometrial hyperplasia. The nomenclature of these hyperplasias is currently under discussion. The highest risk for metachronous carcinoma is associated with atypical hyperplasia of the endometrium as detected in fractional curettings. In postmenopausal patients treatment should consist of abdominal hysterectomy. The so-called type 2-carcinomas, serous-papillary and clear-cell type, do not demonstrate a similar association with precursor lesions. Pathological findings in patients treated with Tamoxifen include endometrial atrophy and fibro-cystic endometrial polyps, sometimes with cellular metaplasias. Patients with breast cancer and tamoxifen treatment have an increased risk of endometrial carcinoma. In some of these patients it could be argued whether the carcinoma has developed in a proceeding endometrial hyperplasia.
Cell Transformation, Neoplastic↗
Clinical relevance of urokinase-type plasminogen activator and its inhibitor type 1 (PAI-1) in squamous cell carcinoma of the uterine cervix.
OBJECTIVE: The expression of uPA and PAI-1 as parameters of tumour-associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. METHODS: Quantitative levels for uPA (n = 114) and PAI-1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA-technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni- and multivariate analysis. RESULTS: Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI-1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut-off level of 2.4 ng/mg protein, patients with elevated PAI-1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI-1. CONCLUSIONS: The results indicate, that PAI-1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence-free survival.
Adult↗
Current awareness in prenatal diagnosis.
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Adult↗
CD44 mediates constitutive type I receptor signaling in cervical carcinoma cells.
OBJECTIVE: The CD44 transmembrane glycoprotein family has been implicated in the growth and metastasis of numerous human cancers. CD44 may function in some cells through interactions with type I receptor tyrosine kinases, including erbB2. Here, we tested whether CD44 interacts with erbB2 and another type I receptor, the epidermal growth factor receptor (EGFR), in human cervical carcinoma tissues and cell lines and whether these interactions influence erbB2 signaling. METHODS: CD44, EGFR, and erbB2 colocalization were examined in 36 pT1b-pT2b cervical cancer cases and in the CaSki and SiHa cervical carcinoma cell lines by immunohistochemistry and laser scanning confocal microscopy. The role of CD44-EGFR-erbB2 interactions in erbB2 signaling was examined by immunoprecipitation and using antisense CD44 oligonucleotides. RESULTS: CD44, erbB2, and EGFR coexpression and colocalization were observed in 42% (15/36) of cervical carcinoma cases and in both cervical carcinoma cell lines. Colocalization occurred to an equivalent extent in all tumor grades examined. CD44 coimmunoprecipitated with erbB2 and EGFR in cervical carcinoma cell lysates, indicating that these proteins interact with each other. Reduction of CD44 expression inhibited constitutive erbB2 activity. High CD44 expression was linked to EGFR activity using dominant negative EGFR, suggesting that type I receptors may autoregulate their activity in these cells. CONCLUSIONS: Our data indicate that CD44 can mediate type I receptor function in cervical carcinoma cells that overexpress both CD44 and either erbB2 or EGFR and suggest a novel mechanism by which these proteins may contribute to cervical carcinoma tumor growth and metastasis.
Cell Division↗
Missed abortion complicated by Candida infection in a woman with rested IUD.
Although Candida species are frequent saprophytes of the female genital tract, chorioamnionitis or intrauterine fetal infections are rarely caused by these fungi. The present report describes a 34-year-old woman G2, P2, presenting with vaginal bleeding in the 11.6 weeks of gestation. Clinical and sonographic examination revealed a missed abortion and rested IUD. Histopathologically, a fungal chorioamnionitis due to Candida spp. was found at the curetting material, confirmed by detection of C. albicans infection on mycological culture. Foreign intrauterine bodies, like IUD's and cerclage sutures predispose to fungal chorioamnitis or fetal infections. This conditions urge repetetive search for Candida spp. to establish early anti-fungal therapy which may be therapeutic for this hithero rare intrauterine infection.
Abortion, Missed↗
Histopathology in rabbit Achilles tendon after operative tenolysis (longitudinal fiber incisions).
The surgical treatment (tenolysis) of chronic Achilles tendinopathy is often successful. However, little is known about the postoperative intratendinous changes after this procedure. The study group consisted of 21 rabbits. Operative tenolysis was done in each case on one Achilles tendon (AT). The ATs of both legs were studied histologically and immunohistochemically using antibodies against collagen types I and III 2, 4 and 6 weeks postoperatively. Nine rabbits without operation served as controls. A significant uniform hypervascularization was noted in the entire operated tendon postoperatively, and this concurred with the contralateral nonoperated AT, but neither side showed changes in collagen fiber structure as judged by immunohistochemistry. We conclude that the tenolysis procedure triggers neoangiogenesis at the AT followed by increased blood flow and improved nutrition in the same. These changes could, at least partly, explain the often seen clinical success in surgically treated tendinopathy.
Achilles Tendon↗
Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis.
A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.
Aged↗
[18F-FDG positron-emission-tomography in cervical carcinoma: preliminary findings].
18F-Fluorodesoxyglucose-Positron-Emission-Tomography (18F-FDG-PET) is a novel imaging modality for malignancies. This study was initiated to define the efficiency of PET in detecting and characterizing metabolically the primaries and in preoperatively assessing of lymphonodal metastases of cervical cancer. 15 patients with histologically proven cervical carcinoma were studied with 18F-FDG-PET regarding 18F-FDG-uptake of primary tumor and evidence as well as extent of lymphonodal metastases. 18F-FDG-PET and histopathological results were compared after radical hysterectomy with pelvic and supplementary in 7 cases paraaortal lymphadenectomy. All primary tumours showed 18F-FDG accumulation and had a mean maximal standardized uptake value (SUV) of 8.0 +/- 5.3. 3/6 lymph node metastases were obtained with 18F-FDG-PET. Micrometastases (size of metastasis < or = 0.2 cm) were present in 2 patients with false negative PET results. Regarding the subgroup with paraaortal lymph node dissection, PET detected one patient with metastases, the other one had micrometastasis, while metastasis was not observed by PET. The accuracy of PET is 73% for assessment of pelvic lymph nodes and 86% for assessment of paraaortal lymph nodes. In conclusion 18F-FDG accumulates reliably in primaries of cervical cancer. Regarding assessment of lymph node metastases PET seems to be of potential use, offering metabolic information independent of the size of metastatic lymph nodes. An improvement of accuracy can be expected if combined evaluation of morphologic and metabolic images is performed.
Adult↗
[Epidemiology and pathogenesis of cervical cancer].
The majority of the estimated incidence of 471,000 new cases for invasive cervical cancer (CX) and 215,000 cancer deaths occurs in the developing countries. For Germany the CX accounts at 8th position of all cancers in women in 1997 with 5,800 newly diagnosed cases. But, every fourth woman between 25th- and 35th-year of life has been affected by CX. This counts at the upper third of the incidence in the European Union (EU). The estimated loss of live-years for women affected by CX is about nine years. The lethality for all stages of invasive cervical cancer is about 30%. For the last two decades stagnation of the reduction of mortality by CX has been reported for EU and the USA, especially affecting woman up to 35th-year of life. The percentage of this age group of all primary operative treated CX at the Leipzig University Hospital between 1979 and 1999 was 26.2%, with a mean age of 43.4 +/- 11.1 years. Improved screening for CX in the western countries and a change in environmental factors have been caused an increase of cervical precancerous (CIN-) lesions. The frequency of CIN-lesions has been estimated to be 100-times higher than the incidence of invasive cancer (21.1) in Germany. The pathogenesis of CX is multistage and CIN I and II represent highly regressive lesions, whereas CIN III requires therapeutic intervention, caused by high progression rate. The Bethesda-classification of low und high grade squamous intraepithelial lesions (SIL) cannot be recommended for biopsies or conisation specimens. Dsyplastic lesions of endocervical columnar epithelium should not be graded, the only general accepted lesion represents the adenocarcinoma in situ (ACIS). Both, CIN and ACIS represents proliferative active lesions, caused by infection with HPV. But the detection of morphologic alterations, associated with HPV, like koilocytes, are inverse correlated with the grade of the CIN-lesion.
Adult↗
[State of art and future prospects in cervical cancer].
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Female↗
[Significance of family anamnesis in cervix carcinoma].
OBJECTIVE: Except for certain types of familiar cancer, the impact and contribution of familial factors to the development of sporadic cancer is thought to be relatively minor. Some earlier case reports had been suspected genetic background in cervical cancer (CX). MATERIAL AND METHODS: The literature was screened and cervical cancer patients from the Department of Obstetrics and Gynecology of the University Hospital of Leipzig were searched for familiar history of malignant tumors at any sites to establish familial risk for CX. RESULTS: Analysis showed, that 15 to 20% of cervical cancer represented at least one first-degree relative with malignant disease any site. The familial relative risk for in situ or invasive CX was reported to range between 1.8 to 2.0 and the heretability was between 0.11 and 0.15 for in situ and 0.22 and 0.33 for the invasive form. In some families a clustering, i.e. two or more female first-degree sibs were affected by CX, was observed, the frequency ranged between 1.7 and 7%. Analyses of risk by age of onset are rarely done and the results are controversy. Two large studies reported an aggregation of tobacco-related and HPV-associated malignancies, like oro-pharyngeal, lung and anorectal sites, in cervical cancer families. Moreover, it has been shown, that both mothers and daughters, who had invasive CX as the first primary cancer, had an excess of lung cancer as a second tumor site. CONCLUSIONS: The correlation of HPV-associated neoplasms in affected families suggest a role of mild or moderate hereditary immunosuppression in explaining a part of familial predisposition to cervical cancer are biologically founded. Consequently, this would not imply germ line mutations in oncogenes or tumor suppressor genes but in genes modulating immune response and perhaps causing susceptibility to a variety of viral infections.
Adolescent↗
[Pathologic-anatomic description and basic morphological information for management of dysplasias and carcinomas of the cervix uteri].
Histopathology is the bedrock and cornerstone in the management of malignant tumors. Careful macroscopic description with selection of representative tissue for histologic examination is required for quality assurance and quality improvement and for assessing prognostic factors in cervical cancer specimens. The pathology report in cervical cancer (CX) should include three-dimensional tumor measurement, the exact measurement of depth of infiltration of the cervical wall, tumor grading, the presence of lymphatic space as well as blood vessel involvement. The statement for resection margins should include the vaginal, parametrane, rectal and vesical direction. All resected lymph node should be counted, measured and processed completely in step sections. If lymph node metastases are diagnosed, the report should include the size and count of metastatic nodes in relation to resected nodes. Pelvic and para-aortal nodes should be reported separately. Lymph nodes in the parametrane tissue represent regional nodes; and metastatic involvement should be stated as pN1 and not as pT2b. The tumor typing and staging should be conform with WHO-classification of malignant tumors and the TNM-classification system. The last one should be used in all cases which were surgically treated. Konizations and LOOP-excision specimens should be processed completely in step sections. The pathology report must include the severity of CIN-lesion, changes caused by HPV-infection, according to colposcopic localisation.
Cervix Uteri↗