Squamous cell carcinoma markers in neoplasms of the uterine cervix

In an extremely well-controlled study, Cohen et al. (1998) add to prior knowledge of stress-illness relationships by showing that self-reports of stress occurrence and duration of 1 month or more, rather than estimates of stressor severity, predict susceptibility to experimentally induced colds (i.e., viral replication and cold symptoms). Although ruling out obvious behavioral and personality factors as causes of the association of stressors to colds, they were unable to identify mediational immune factors, a deficit attributable to the difficulty of assessing the multi-layered, dynamic physiological processes within the bidirectional connections of the nervous (stress) and immune systems. The findings provide an interesting complement to data, showing that people use stressor duration in evaluating the illness implications of somatic symptoms (Cameron et al., 1995), and suggest caution with regard to overestimating the prevalence of stress-induced colds in natural settings.     

Small cell carcinoma of the uterine cervix: a clinicopathological review

Small cell carcinoma of the cervix is rare, with an aggressive natural history. We report on a series of 11 patients treated at the Christie Hospital, Manchester and examine their treatment and survival. Eleven patients with small cell carcinoma of the cervix were identified retrospectively from patient case notes. Treatment was individualised and included a variety of combinations of surgery radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108 months (crude disease-free survival 36%). They presented with earlier disease and were older than the average for the group. They were all initially treated with radical radiotherapy. 7 patients died between 7 and 25 months. Despite combination chemotherapy, survival with advanced disease was poor. Published studies are small and fail to provide definitive answers on the best management of small cell carcinoma of the cervix. Drawing on the experience of small cell carcinoma of the lung however, combination therapy with radiotherapy, chemotherapy and possibly surgery requires careful assessment by an oncologist.     

Papillary squamous cell carcinoma of the uterine cervix: diagnostic pitfalls

BACKGROUND: In 1989, a Boeing 737-400 aircraft crashed at Kegworth, near Nottingham, England. The survivors suffered a large number of pelvic and lower limb injuries, and approximately one-third of the passengers died. Subsequent research has suggested that the "brace-for-impact" position that passengers are advised to adopt prior to a crash landing might be modified in order to reduce the incidence of such injuries. The aim of this research was to evaluate biomechanically such a modified crash brace position. HYPOTHESIS: A modified brace position would help to prevent injuries to some passengers in the event of an impact aircraft accident. METHODS: Impact testing on forward-facing seats was performed at the Royal Air Force Institute of Aviation Medicine, Farnborough, England. Aircraft seats, mounted on a sled, were propelled down a track to impact at -16 Gx. A test dummy was used as the experimental model. Four dummy positions were investigated: a) upper torso braced forward and lower legs inclined slightly rearward of the vertical; b) upper torso braced forward and lower legs inclined forward; c) upper torso upright and lower legs inclined slightly rearward of the vertical; and d) upper torso upright and lower legs inclined forward. The impact pulses used were based on Federal Aviation Administration guidelines. Transducers located in the head, spine, and lower limbs of the dummy recorded the forces to which each body segment was exposed during the impact. These forces were compared for each brace position. RESULTS: Impact testing revealed that the risk of a head injury as defined by the head injury criterion was greater in the upright position than in the braced forward position. The risk of injury to the lower limbs was dependent in part on the flailing behavior of the limbs. Flailing did not occur when the dummy was placed in a braced, legs-back position. CONCLUSIONS: A modified brace position would involve passengers sitting with the upper torso inclined forward so that the passenger's head rested against the structure in front, if possible. The legs would be positioned with the feet resting on the floor in a position slightly behind the knee. The position differs from those previously recommended in that the feet are positioned behind the knee. This study suggests that such a position would reduce the potential for head and lower limb injury in some passengers, given that only a single seat type and single size of occupant have been evaluated. Standardization to such a position would improve passenger understanding and compliance. Such a recommendation should not obscure the fact that an occupant seated in a forward-facing aircraft seat, restrained only by a lap belt, is exposed to considerable forces during an impact accident. Such forces are capable of producing injuries in the femur, pelvis, and lumbar spine.     

Chemoradiotherapy in cancers of the uterine cervix

In order to determine the possible role of the cystic fibrosis transmembrane regulator (CFTR) gene in pulmonary diseases not due to cystic fibrosis, a complete screening of the CFTR gene was performed in 120 Italian patients with disseminated bronchiectasis of unknown cause (DBE), chronic bronchitis (CB), pulmonary emphysema (E), lung cancer (LC), sarcoidosis (S) and other forms of pulmonary disease. The 27 exons of the CFTR gene and their intronic flanking regions were analyzed by denaturing gradient gel electrophoresis and automatic sequencing. Mutations were detected in 11/23 DBE (P = 0.009), 7/25 E, 5/27 CB, 5/26 LC, 5/8 S (P = 0.013), 1/4 tuberculosis, and 1/5 pneumonia patients, and in 5/33 controls. Moreover, the IVS8-5T allele was detected in 6/25 E patients (P = 0.038). Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. These results confirm the involvement of the CFTR gene in disseminated bronchiectasis of unknown origin, and suggest a possible role for CFTR gene mutations in sarcoidosis, and for the 5T allele in pulmonary emphysema.     

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.     

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.     

Sonographic evaluation of the uterine cervix

Ultrasonographic evaluation of the uterine cervix has been shown to help predict patients who may be at an increased risk for preterm delivery. The use of ultrasound in at-risk patients may improve the selection of those needing obstetric intervention, which therefore, may improve outcome and lower overall health care costs. Cervical competence, once thought to be a categorical variable, should now be thought of as a continuous variable, as the shortest cervical lengths are found in those women with a history of very early preterm delivery (> 24 weeks). Adjunctive tests, such as fetal fibronectin Bishop scoring and bacterial vaginosis may help to improve the accuracy of prediction of preterm birth; therefore a multifaceted risk approach to preterm birth is suggested in this article.     

Alveolar rhabdomyosarcoma of the uterine cervix

Porphyria cutanea tarda is characterized by severe connective tissue damage in sun-exposed skin. The regulated synthesis and degradation of the extracellular matrix by various matrix metalloproteinases (MMPs) determine its amount and composition within the skin. In this study, we therefore asked whether long-wave ultraviolet irradiation (340-450 nm) in conjunction with uroporphyrin I could modulate the synthesis of MMPs with substrate specificities for dermal (collagens I, III, V; proteoglycans) and basement membrane components (collagens IV, VII; fibronectin; laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases is also affected. After irradiation of uroporphyrin-pretreated fibroblasts, specific mRNAs of MMP-1 and MMP-3 increased concomitantly up to 2.7-fold compared with ultraviolet-irradiated cells and up to 10-fold compared with mock-irradiated or uroporphyrin I-treated controls. In contrast, mRNA levels of tissue inhibitor of metalloproteinases remained unaltered. Similar results were obtained by immunoprecipitation. Gelatin and casein zymography revealed increased proteolytic activity of MMP-2 and MMP-3 in blister fluids of patients with porphyria cutanea tarda, indicating that similar events may occur in vivo. Using deuterium oxide as enhancer and sodium azide as quencher of singlet oxygen, we could increase or reduce MMP synthesis, suggesting that singlet oxygen is the major intermediate in the upregulation of MMPs after irradiation of uroporphyrin-pretreated fibroblasts. Taken together, our results show that ultraviolet irradiation alone, and to a greater extent in conjunction with uroporphyrin I, results in an unbalanced synthesis of MMPs that may contribute to the destruction of the dermis and basement membrane, leading to blistering and accelerated photoaging in porphyria cutanea tarda patients.     

Diagnostic conization of the uterine cervix. II. Comparison of histological diagnoses with cytological and colposcopic tentative diagnoses

This report presents colposcopic and cytologic misinterpretations in cases with a cervical intraepithelial neoplasia or early invasive carcinoma and benign cervical lesions and the accuracy of these two methods of screening for cervical cancer. The accuracy of the cytology and of the colposcopic impression in predicting the degree of cervical intraepithelial neoplasia and early invasive carcinoma was over 93 per cent. In patients showing benign cervical lesions the cytology is more accurate in predicting the correct histologic change with 94,2 per cent than the colposcopic impression with 63,1 per cent. The suspicious smears (Papanicolaou III) are discussed.     

The problem of replacement and differentiation of the intestinal epithelium: its relation to squamous metaplasia in the uterine cervix

This study investigates the professional characteristics of care staff working in group homes for the mentally ill in a north London region. Opportunities for training and staff attitudes with respect to training and career prospects are examined. The majority of care staff are unqualified and in many cases the training needs of staff are not being met. Staff viewed their career prospects as limited. Training that is on offer to staff in principle is often not accessed, possibly owing to budget restrictions. The need for more stringent guidelines on staff training to maintain standards across agencies is highlighted.     

A case of small cell carcinoma of the uterine cervix presenting Cushing''s syndrome

GABAA agonists do not respond to the same degree to allosteric modulators of the GABAA receptor complex such as benzodiazepines. We report there the effects of two steroids (alfaxalone and pregnenolone sulfate) on the inhibition induced by two GABAA agonists, 3-amino propane sulphonic acid (3-APS) and muscimol, on the extracellular evoked potentials obtained in CA1 of mice hippocampi. Alfaxalone (1 microM) potentiates the effects of both agonists, although incubation times longer than 15 minutes are required to potentiate the inhibitory effect of muscimol. Lower doses of pregnenolone sulfate at shorter incubation periods are able to inhibit the effects produced by single doses of 3-APS as compared to muscimol (15 microM during 5 min vs 30 microM during 5 min). Our results confirm the possibility that there might be differences in the interaction between GABAA agonists and modulatory steroids.     

Clear cell adenocarcinoma of the uterine cervix: a histological and histochemical study

A case of Mullerian clear cell adenocarcinoma of the uterine cervix occurring in a young women is presented. A detailed histological and histochemical study of this type of tumour is important so as to separate it from the clear cell tumour of mesoenphric origin. The association of Mullerian clear cell adenocarcinoma and other abnormalities of the vagina and cervix with the administration of maternal nonsteroidal oestrogens has been recently stressed in the literature. However, our patient is illustrative of the 30-50% of cases reported to date which have few if any of the associated abnormalities of the genital tract and have no known exposure to non-steroidal oestrogens.     

Neuroendocrine differentiated carcinoma of the uterine cervix

Cervical neuroendocrine carcinomas (CNC) are rare tumors. The term includes the cervical carcinoid, the small cell (oat-cell) carcinoma and the primitive neuroectodermal tumor (PNET). Between 1979 and 1993 eight CNC out of 788 cervical carcinomas were identified by conventional light microscopy and immunohistochemistry. Three tumors were small cell carcinomas with positive staining for NSE (6/8 tumors) and chromogranin A (2/8). In one case a PNET was diagnosed by identifying rosette like structures and negative immunohistochemistry for neuroendocrine markers. Two patients (including PNET) died of disease 3.1 (1.3 to 4.8) years after diagnosis. The others showed no evidence of disease after a mean follow up to 4.4 years. Three of them got pelvic radiation postoperatively. Four tumors showed foci of squamous cell carcinoma [3] and adenocarcinoma [2]. There is no evidence, that these foci influence the prognosis on CNC. Therefore, it is important to recognize the neuroendocrine component, as this type of carcinoma requires special therapeutic considerations. The authors favour the metaplastic origin of CNC from a multipotent (endocervical) stem cell.     

Differential transforming growth factor-beta secretion in adenocarcinoma and squamous cell carcinoma of the uterine cervix

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.