Management of cervical neoplasia with colposcopy

During a 44-month period the introduction of colposcopy to a metropolitan dysplasia clinic resulted in 1, 144 colposcopic examinations on 442 patients. Agreement between colposcopically directed biopsy and final diagnosis was found in 84%, and directed biopsy revealed the most advanced lesion in 42.5%. Satisfactory colposcopy was performed on 93% of patients, and some degree of histologic abnormality was obtained in 86% of patients with colposcopic abnormalities. Undetected invasive cervical cancer occurred in both cervical conization and colposcopic examinations with equal frequency. Endocervical curettage detected two cases of occult invasive cancer, and increased use of this procedure is recommended. Guidelines for management of cervical neoplasia are suggested.     

Lack of effect of coumarin on unscheduled DNA synthesis in precision-cut human liver slices

OBJECTIVE: To evaluate the accuracy of cytologic screening in pregnancy through routine colposcopy and to confirm the safety of conservative management of cervical intraepithelial neoplasia (CIN) in pregnancy. STUDY DESIGN: In total, 3,658 pregnant women, screened for cervical cancer with either cytology or colposcopy, were prospectively evaluated. Patients with abnormal findings underwent colposcopically directed biopsy and, in case of CIN, repeat cytology and colposcopy. Biopsy was repeated in case of suspected progression of the lesion. Suspected microinvasion was the only reason for diagnostic conization during pregnancy. After delivery, excisional treatment provided a final specimen from all patients. Diagnostic methods were compared. RESULTS: Comparison between cytology and colposcopy showed 97.1% concordance with a few false positives (2.5%) and false negatives (0.2%). Abnormal cytology and colposcopy, as compared with histology, showed similar concordances, but the risk of underestimation by cytology was significantly higher (P < .05). Initial and final histology of the 63 cases of CIN and microinvasive carcinoma showed 88.9% concordance. Progression of the lesion was not observed. CONCLUSION: These data do not justify combined use of cytology and colposcopy to improve screening for cervical cancer in pregnancy. Delayed treatment of CIN after delivery is safe.     

The "unsatisfactory" colposcopic examination

One hundred nine of 735 patients (14.8%) referred for colposcopic evaluation had "unsatisfactory" examinations. Of 108 women 40 years of age or over, 81 had unsatisfactory examinations (45%) as compared with 28 of 555 women under 40 (5%) (p less than 0.001). Thirty-five of the 109 patients with unsatisfactory examinations (32%) had had prior cautery or conization as compared with 141 of 626 in the "satisfactory" group (22.5%) (p less than 0.04). Seventy-three of the 99 patients on whom follow-up information was obtained had cervical conization biopsies for final diagnoses. Correlation with previously performed endocervical curettage and colposcopically directed biopsies was poor. Careful correlation of cytology, colposcopy and histopathology is necessary to achieve optimal results in the management of patients with unsatisfactory examinations. Diagnostic conization continues to play an important role in the management of patients with abnormal cervical cytology.     

Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes

One hundred and sixty-eight cases of cervical conization were performed for cervical intraepithelial neoplasia (CIN) in a 32-month study. The indications for conization were unsatisfactory colposcopic finding, abnormal epithelium that extended into the endocervical canal, a microinvasive cervical cancer, and significant discrepancy among cytology, colposcopy, and/or punch biopsy histology. In the early period of the study, conization was done by the cold-knife method (N = 107), whereas loop diathermy was used in the latter part of the study (N = 61). Both groups were similar in terms of age, indications for conization, and size of cervical cone specimens. Loop diathermy conization was done in a significantly shorter time (5.7 +/- 1.8 minute vs 15.2 +/- 6.1 minute)(P < 0.05) than cold-knife conization. However, the difference in the postoperative complications between loop diathermy(3.0%) and cold-knife conization(4.7%) was not significant. The incidence rate of residual CIN III lesions in the subsequent hysterectomy specimens, found by histological documentation on these specimens was 25.0 and 26.1 percent after loop diathermy and cold-knife conization respectively. These results suggest that loop diathermy is much easier to perform and a more time-conserving treatment modality than cold-knife conization in the management of patients with cervical intraepithelial neoplasia.     

Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.     

Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population

The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.     

Colposcopic evaluation of patients with abnormal cervical cytology

A total of 1580 new patients underwent colposcopic evalution in the Dysplasia Clinic at Nassau County Medical Center. Of these patients, 186 had abnormal Papanicolaou smears associated with pregnancy, 150 were referred because of in utero exposure to diethylstilbestrol, and 1244 were referred because of abnormal cervical cytologic smear or suspicious cervical or vaginal lesion. Further analysis of this latter group revealed that 1184 (95%) patients had satisfactory colposcopic evaluation, and directed biopsy showed the following: 10 cases of invasive cervical carcinoma, 9 of carcinoma in situ with microinvasion, 118 of cervical carcinoma in situ, 110 of severe dysplasia, and 424 cases of mild to moderate cervical dysplasia. All of these patients subsequently were treated accordingly. Evaluation of final histologic specimen revealed a very high correlation with colposcopically guided biopsies. In 54 patients, where colposcopic evaluation was unsatisfactory, diagnostic cold knife conization was performed. Final histologic diagnosis disclosed a more advanced lesion in 30 patients (or 56%) of this group. The result of this study shows that satisfactory colposcopic evaluation is a highly accurate method of evaluation of abnormal cervical and vaginal cytologic smear.     

Osteochondritis dissecans of the humeral head

ISSUES: The colposcope was developed in 1925 and is well established in clinical gynecologic practice for defining and delineating cytologically detected lesions mainly of the cervix but also the vagina and vulva. Additionally, various endoscopic procedures in gastroenterology, pulmonary and urologic lesions enhance the cytologic detection and histologic verification of precancerous and cancerous lesions. The cost-effectiveness of all these devices and their applicability, particularly in countries with a limited health budget, is a major issue. This task force considered aspects of the present state of the art and the challenges in the 21st century. CONSENSUS POSITION: Automated cytology can interface with colposcopic examination in a number of significant ways. Automated cytologic analysis of conventional cervical smears can potentially direct colposcopic examination by predicting the nature of a lesion, assist in determining which patients should receive colposcopy and, in some settings, thereby reduce the number of colposcopies. Potentially, various combinations of automated cytology and colposcopy may be used to generate screening protocols that might result in more effective and inexpensive screening. The role of cervicography, or high-resolution cervical photography, as a screening device remains to be defined. Sensitivity for high grade lesions is generally no greater than that in cytology, and specificity appears lower. The interpretation of cervical photographs in triage of mildly abnormal cytology may prove to be useful in countries with established cytology programs. In areas of the world where cytology screening programs are not in place, the interpretation of cervical photographs may have its most dramatic effect. Cost-effectiveness analyses are needed. There are, at present, insufficient data for the evaluation of speculoscopy, a procedure using chemiluminescent illumination of the cervix for visualization of acetowhite areas. Basic training in colposcopy should be integrated into the residency programs of obstetrics and gynecology. Criteria for the adequate training of colposcopists should be developed. Continuing education programs in colposcopy should be developed when they are not already in existence. The cost-effectiveness of integrating colposcopy as a primary screening technique should be evaluated. Following a high-grade squamous intraepithelial lesion (HSIL) cytology result, colposcopically directed punch biopsy should be taken with or without endocervical curettage. This generally should precede the loop electrosurgical excision procedure (LEEP); however, in certain circumstances direct LEEP may be indicated. LEEP under colposcopic vision is an efficient way to treat an HSIL lesion of the cervix because the histologic extent and margins can be determined, unlike with laser surgery or cryosurgery. It is also more cost-effective than cold knife conization because general anesthesia and an operating room are unnecessary. Following LEEP, the endocervical canal should be examined colposcopically for any evidence of involvement. Lesions in the endocervix can then be removed with a different-shaped loop. Further research into Raman spectroscopy as a diagnostic aid in cervical pathology is needed, as is the use of micrococolpohysteroscopy for in vivo cytologic analyses, especially of the endocervical canal and transformation zone. Hysteroscopy is the most direct method for the diagnosis and treatment of intrauterine diseases. Hysteroscopic endometrial biopsy is more accurate than conventional biopsy methods. Cervical invasion of endometrial cancer can be detected by hysteroscopy. The depth of invasion, however, is more accurately determined by magnetic resonance imaging or computed tomography. ONGOING ISSUES: Many topics for ongoing research and/or implementation are mentioned under "Consensus Position," above. (ABSTRACT TRUNCATED)     

Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear

OBJECTIVE: To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear. DESIGN AND SETTING: Prospectively collected cervical samples were split for independent screening at a large specialised private gynaecological pathology practice in Sydney. MAIN OUTCOME MEASURES: Detection of additional significant abnormalities (cervical intraepithelial neoplasia 1, or more severe); changed management recommendations from "repeat smear in 12 months" or "...six months" to "colposcopy", a reduction in unsatisfactory reports. RESULTS: 35,560 paired (split-sample) conventional and ThinPrep slides were prepared. Significant abnormalities were detected in 724 conventional smears (2%). Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review, representing a 12% increase in the detection of significant abnormalities. As a result of the addition of ThinPrep, management recommendations were changed from "repeat smear in 12 months" or "...six months" to "colposcopy" for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus. There were 1258 conventional smears (3.5%) that were unsatisfactory compared with 235 ThinPrep slides (0.7%); for only 74 samples (0.2%) were both slides unsatisfactory. CONCLUSIONS: The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities, and reduces the number of unsatisfactory samples which would otherwise require repeat tests.     

What is the appropriate management of early stage cervical cancer (International Federation of Gynecology and Obstetrics stages I and IIA), surgical assessment of lymph nodes, and role of therapeutic resection of lymph nodes involved with cancer?

It is well recognized that lesion size, tumor volume, depth of stromal invasion, and lymphatic space permeation are all important predictors of lymph node involvement in early stage cervical cancer. Pelvic lymph node involvement is the most important (negative) predictor of survival for these patients with early stage cervical cancer. The number of involved nodes and the size of involved and unresected nodes may also be prognostically significant. It is uncertain whether lesion size, tumor volume, depth of stromal invasion, or lymphatic space permeation are independent negative predictors of survival when correcting for lymph node positivity. Lymphadenectomy has traditionally been considered a diagnostic procedure. There is accumulating evidence to suggest that lymphadenectomy may have therapeutic benefit for patients with cervical cancer metastatic to lymph nodes. This hypothesis awaits further evidence.     

Radical hysterectomy with pelvic lymphadenectomy in patients with carcinoma of the uterine cervix--3 years' experience

INTRODUCTION: Almost all patients with invasive cervical carcinoma can be treated with either primary irradiation therapy or primary surgery. Some patients are appropriately treated with the combination of irradiation and surgery. Chemotherapy is not effective as primary treatment of invasive cervical cancer but may be used as additional therapy and when the disease is recurrent or persistent. There are some important advantages of primary extensive surgery over irradiation. The findings at operation and that from the careful pathologic examination of surgical specimens can be very helpful in selection of patients for supplementary postoperation irradiation therapy or chemotherapy, or both [1-6]. AIM OF THE STUDY: The aim of the study was to compare pretreatment clinical evaluations with surgical and postsurgical pathohistological findings. METHODS: Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. The patients were treated at the Department of Obstetrics and Gynaecology of the Clinical Centre of Serbia in Belgrade, between 1993 and 1995. Cervical cancer was detected by clinical examination, colposcopic and cytologic (Pap smear) findings, colposcopically directed biopsy or conisation and pathological findings, sonography, chest radiography, blood and urine analyses. In some cases we had to make other examinations (cystography, cystoscopy, intravenous pyelography, sygmoidoscopy, rectoscopy, CT scanning and magnetic resonance). The surgical treatment of invasive carcinoma of the cervix was limited to those patients in whom the disease was confined to the cervix or vaginal fornix (stage Ia, stage Ib or stage IIa), and who were in high surgical risk. RESULTS: Over a three year period (1993-1995) there were 251 patients with invasive cervical cancer, treated by primary surgery (radical hysterectomy and bilateral pelvic lymphadenectomy sec. Werthein-Meigs), average age 42 years. Most of the patients demonstrated invasive cervical cancer, clinically classified in Ib st. (81.67%). Some characteristics of pathologic findings, such as parametric width, number of removed lymph nodes, percentage of lymph nodes metastases and correlation with clinical stage of invasive cervical cancer, histologic grade of cervical cancer with lymph node metastasis, pathologic findings after surgical treatment, correlation between clinical and surgical staging, were already presented in tables. DISCUSSION: In the last decades the incidence of invasive cervical cancer and death rate have been decreased. Progress in reducing mortality is primarily attributed to the introduction of cervical cancer screening as part of regular gynaecologic examinations. Regular testing with Papanicolaou (Pap) smear and colposcopy have an important role in this problem [1]. Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. We found that the clinical diagnosis of disease extent was correct in 67.7% of patients who underwent extensive surgery for early invasive cervical cancer. Sensitivity of clinical findings was 75.8% and positive predictive value was 86.2%. Lymph node metastasis was detected in 17% patients. Brodman at al. [14] found that clinical examinations, including CT scanning and magnetic resonance, were correct in only 62.5% of cases. It is very difficult to detect parametric involvement and lymph node metastasis by clinical examinations. Irradiation therapy was used in the postoperative period as additional treatment of extensive hysterectomy and bilateral pelvic lymphadenectomy in 89.7% of patients. CONCLUSION: The findings at operation and that from the careful pathologic examination of surgical specimens are absolutely irreplaceable and important in grading invasive cervical cancer and selection of patients for supplementary postoperate irradiation therapy.     

Natural history of false-negative papanicolaou smears: a prospective study using screening colposcopy in addition to cytology

The regular Papanicolaou (Pap) smear is cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high rate of false-negative results; therefore, serial examinations are necessary for optimal sensitivity. The sensitivity of the routine pelvic examination is further increased with the addition of colposcopy to cytologic screening. Patients identified as having disease by colposcopy and biopsy but not by Pap smear (false-negative), are followed up, and the progression of their disease is documented until the Pap smear reflects the known change. A total of 276 patients whose Pap tests showed "no abnormal cells" and mild dysplasia (CIN-1 [cervical intraepithelial neoplasia]) by colposcopy and biopsy, who opted not to be treated, were followed up as a function of time. The results of the Pap test on the 276 patients progressed to a low-grade squamous intraepithelial lesion (LGSIL) or higher within 42 months. In this study, false-negative Pap tests that were identified by simultaneously performed colposcopy became positive within 42 months; therefore, careful repetitive screening is necessary. The author argues that a definitive, prospective study on the addition of colposcopy or similar adjunct procedure to the routine pelvic examination, in selected cases, is needed.     

Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection

Many studies have shown a strong correlation between CIN and HPV infection. Molecular biology has allowed identification of types of HPV which seem to be connected, more frequently than others, to dysplastic lesions. Physical state of HPV-genome seems to play an important role in the development of cervical cancer. In this study the HPV-genome has been searched in tissue specimens obtained from 34 women affected by CIN II and III. All patients underwent laser conization. Immediately before treatment, colposcopically directed biopsies of the cervical lesion and of the areas with no colposcopically apparent disease were taken and on these samples, HPV-DNA has been searched, isolated and analysed for HPV types and physical state. Histologic examination on cones showed 6 cases of CIN II (3 with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3 with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the other 3 cases of CIN III showed both integrated and episomal HPV-genome. Integrated form has been noticed only for HPV 16 type. In no case of colposcopically normal tissue has HPV-DNA been found. These data seem to confirm the strong correlation between HPV 16 type, which often has integrated form, and CIN III strengthening the hypothesis of its potential oncogenic action.     

Clinical Significance of a cervical cytologic diagnosis of atypical squamous cells of undetermined significance. Favoring a reactive process or low grade squamous intraepithelial lesion

OBJECTIVE: To define the clinical significance of qualifying the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) as favoring either a reactive process or a low grade squamous intraepithelial lesion (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of 118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring either a reactive process or LSIL were evaluated in our colposcopy clinic by repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic diagnosis of ASCUS favoring a reactive process had a repeat smear that was normal. None was found to have CIN. Of the 60 patients who had a cervical diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity of a repeat smear, in this limited series, after an initial smear of ASCUS favoring a reactive process is 100%, while it was 66% after an initial smear of ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is associated with a very low risk that the patient is haboring CIN. In the patient whose initial smear shows ASCUS favoring a reactive process, a repeat smear that is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL probably requires further evaluation even in the presence of a normal repeat smear.     

Predictive value of early postoperative esophagoscopy for occurrence of benign stenosis after cervical esophagogastrostomy

BACKGROUND AND STUDY AIMS: Benign anastomotic stenosis (BAS) represents a frequent complication following esophagectomy and cervical esophagogastrostomy for cancer. This study was undertaken to evaluate through early postoperative esophagoscopy the morphologic change of the anastomosis which could be related to BAS development. PATIENTS AND METHODS: Thirty-nine patients who underwent subtotal esophagectomy and cervical esophagogastrostomy were prospectively evaluated. The analyzed factors were: age; sex; the anastomotic size; the presence and number of endoscopically visible stitches; the presence and percentage of mucosal ulcerations involving the anastomotic suture line; the presence of anastomotic leak or dehiscence; the vascularization of the gastric tube; the patency of pylorus. RESULTS: No complications related to the early esophagoscopy were observed. Twelve patients (30.7 %) developed a stenosis postoperatively. The univariate analysis demonstrated anastomotic leak (p < 0.006), more than one endoscopically visible stitch (p < 0.0003), and mucosal ulceration involving more than 50% of the anastomosis (p<0.00009) as factors significantly correlated with BAS development. However stepwise logistic regression extracted the presence of ulcerations involving more than 50% of the anastomosis as the most important independent factor in predicting BAS development (Odds Ratio = 9.03+/-5.5, p = 0.009). All patients who developed a BAS were treated with early pneumatic dilatations, with an 83.3% success rate after a mean of 3.6 sessions. CONCLUSIONS: Early postoperative esophagoscopy seems a safe and effective tool for the monitoring of the anastomosis healing after cervical esophagogastrostomy. The presence of extended mucosal ulcerations appeared as the most important factor in predicting BAS formation.     

Interstitial muscle insulin and glucose levels in normal and insulin-resistant Zucker rats

Tumour angiogenesis (antifactor VIII-related antigen antibody), p53 overexpression (DO-1) and proliferative activity (MIB-1) were immunohistochemically analysed for the prediction of long-term survival in 113 patients with squamous cervical carcinoma. The median follow-up time was 82 months (range 72-99). In early stages (IB-IIA), neovascularisation was significantly related to tumour size. Significantly more patients in stage IIA had high tumour vascularity compared to stage IB (P < 0.01) but no significant difference was found between early and advanced stages (IIB-IVB) of cervical carcinoma. p53 overexpression was correlated to the stage of disease (P < 0.01). No relationship was found between tumour angiogenesis, p53 overexpression or MIB-1 and pelvic lymph node metastases, histological subtype or differentiation. Tumours with more than 50% p53 overexpression was significantly correlated with survival in the univariate analysis, but no independent predictive value was found. It is concluded that immunohistochemically detectable p53 overexpression as measured by DO-1 and proliferative activity as measured by MIB-1 seems of no clinical value for the prediction of long-term survival in squamous cervical carcinoma. The predictive value of tumour angiogenesis for survival outcome has still to be determined in squamous cervical carcinoma.     

Cervical tissue and plasma concentrations of alpha-carotene and beta-carotene in women are correlated

Results from epidemiologic studies suggest that a carotenoid-rich diet may reduce risk for cervical cancer, possibly by inhibiting the progression of cervical intraepithelial neoplasia, a preneoplastic lesion of the cervical tissue. Laboratory studies suggest that the mechanism may be linked to the metabolism of carotenoids to retinoic acid or retinoic acid-like compounds, which has been hypothesized to occur in the cervical tissue. The purpose of this study was to demonstrate the presence of provitamin A carotenoids in biopsied samples of this peripheral tissue in human subjects and to examine the relationship between baseline concentrations of these carotenoids in plasma and normal cervical tissue in subjects who were being evaluated for possible participation in a diet intervention trial. Subjects were 13 women aged 19-41 y. With the use of HPLC methodology, plasma concentrations of alpha-carotene, beta-carotene and beta-cryptoxanthin were determined with UV/visible light detection for plasma and electrochemical detection for cervical tissue. Relationships between plasma and cervical tissue were evaluated with Pearson correlation analysis. Adjusted for plasma cholesterol concentration, plasma alpha-carotene and beta-carotene were correlated with cervical tissue concentrations (r = 0.91, P < 0.001; r = 0.90, P < 0.001; respectively). Adjusted for plasma cholesterol concentration, plasma beta-cryptoxanthin tended to be correlated with cervical tissue concentrations (r = 0.62, P = 0.058). These findings suggest that plasma concentrations of alpha-carotene and beta-carotene are good predictors of cervical tissue concentrations of these compounds in human subjects and describe a first step toward demonstrating a biological link between provitamin A carotenoids and cervical cancer in vivo.     

Radiation therapy results for patients undergoing inappropriate surgery in the presence of invasive cervical carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinoma in situ (36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P = 0.0000) and preoperative diagnosis (P = 0.0021). Tumor histology was marginally significant factor (P = 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P = 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

The potential of serum levels of soluble tumour necrosis factor receptor I as a biochemical marker in cervical cancer

OBJECTIVES: To investigate the significance of serum levels of soluble tumour necrosis factor receptor I (sTNF-RI) as a potential biochemical marker in women with cervical cancer. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-one women with cervical cancer and 33 women with myoma were enrolled in this study. METHODS: Pre-operative serum levels of sTNF-RI were measured with a standard enzyme-linked immunosorbent assay utilising murine monoclonal antibody against sTNF-RI. MAIN OUTCOME MEASURES: All data in both groups were evaluated and correlated with the pre-operative serum levels of sTNF-RI. Data analysis was carried out using ANOVA with multiple comparison and linear regression. RESULTS: The mean serum level of sTNF-RI in the cervical cancer group was significantly lower than that in the myoma group (P < 0.001). The sTNF-RI levels decreased sequentially with disease progression from Stage Ia to IIb in women with cervical cancer. The mean serum level of sTNF-RI was also significantly lower in women with positive lymph node (P < 0.05) or recurrent cancer (P < 0.001). A negative correlation was observed between serum levels of sTNF-RI and tumour size (r = -0.622, P < 0.0001). CONCLUSIONS: Decreased pre-operative serum levels of sTNF-RI are observed in women with cervical cancer. The results do not support that the use of sTNF-RI as a biochemical marker for cervical cancer.     

Expression of carbohydrate antigen sialyl Le(a): a new functional prognostic factor in gastric cancer

PURPOSE: The prognostic value of the altered expression of carbohydrate antigens sialyl Le(a) (sLe(a)) and sialyl Le(x) (sLe(x)), which have been implicated as functional ligands in heterotypic-cell-adhesion systems in the multistep process of tumor metastasis, were evaluated. PATIENTS AND METHODS: The level of expression of sLe(a) and sLe(x) antigens was examined immunohistochemically in paraffin-embedded tumor samples from 137 patients who underwent resection for gastric cancer. Correlation between the antigens' expression, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. RESULTS: Tumors that were positive for the sLe(a) antigen were significantly more likely to be large (P = .035), to be localized at the proximal third of the stomach (P = .018), to have an infiltrate appearance (P = .013), to have an invasive mode both in depth of invasion (P = .028) and in lymphatic invasion (P = .002), and to be classified as late stage (P = .011) than those that were negative for sLe(a), whereas the sLe(x) antigen status was not correlated with any clinicopathologic factors. The overall survival of patients with an sLe(a)-antigen-positive tumor was significantly poorer than that of those with an sLe(a)-antigen-negative tumor (P = .0001). Survival within each pathologic stage differed also (stage I, P = .030; stage II, P = .046; stage III, P = .026, respectively). A Cox regression analysis with multiple covariates showed that positive sLe(a) antigen status was an independent prognostic factor for a worse outcome in patients with gastric cancer. According to the mode of recurrence, increased sLe(a) antigen expression significantly affected both peritoneal dissemination and liver metastasis. CONCLUSION: Increased expression of the sLe(a) antigen may serve as a potent prognostic indicator for recurrence in patients with gastric cancer. Careful follow-up and intensive therapy are required for patients with an sLe(a)-antigen-positive gastric cancer.