Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series.

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.

Population study in the high natural background radiation area in Kerala, India.

A comprehensive survey of the population exposed to high-level natural radiation is presented. The population living in Karunagappally taluk in Kerala, India, presents a unique opportunity for studies on the health effects of chronic exposure to low-level radiation. The environmental radiation emanates largely from the thorium deposited mostly along coastal areas. In certain locations on the coast, it is as high as 70 mGy/year and on average is 7.5 times the level seen in interior areas. Using portable scintillometers, radiation levels in more than 66,306 houses were measured; outside levels were also measured in the same house compound. Of the total population of 400,000, 100,000 lived in areas with high natural radiation. Information on lifestyle, socio-demographic features, occupation, housing, residence history, and tobacco and alcohol use was obtained by house-to-house visits and enumeration of every resident individual. A population cancer registry system has been established to obtain cancer incidence rates. In this preliminary analysis, there is no evidence that cancer occurrence is consistently higher because of the levels of external gamma-radiation exposure in the area. Further dosimetry-level studies are needed along with biological studies. Studies of soil, thoron-in-breath, and the radon-thoron levels in houses are ongoing, and further case-control analyses are continuing.

Risk factors for cervical dysplasia in Kerala, India.

A study in Kerala, India, confirmed the importance of genital hygiene in the fight against infections that have a role in the development of cervical dysplasia and cancer. Many women cannot afford sanitary pads, while adequate facilities for washing after coitus are often unavailable. Health education, satisfactory living standards, and the empowerment of women are prerequisites for reducing the incidence of cervical dysplasia.

PIP: In India, cancer of the uterine cervix is the most often seen cancer in women. There are no organized community-based screening programs, mainly because of a lack of resources and a low level of awareness in the population. Findings are presented from a 2-year study in Kerala, India, of the role of genital hygiene and other sexual and reproductive risk factors in cervical dysplasia. 3450 female outpatients of mean age 39.5 years attending the Women and Children's Hospital, Thycaud, Trivandrum, were interviewed, of whom all but 15 were married. 68% of women under age 50 years had been sterilized postpartum, while 2.3%, 0.3%, and 1.8% of women used barrier contraception, oral contraception, and IUDs, respectively. The husbands of 2.3% of the women had undergone vasectomy and no contraception was used by 26% of the women. 33% of the women presented with vaginal discharge, the most common presenting symptom, and lower back pain was experienced by 16%. 70% reported always washing themselves after coitus, but only 8% reported using sanitary pads during menstruation. 93% of women who used sanitary pads had been educated in high schools or colleges. Inflammation was evident in 70% of smears overall; more than 80% of younger women and around 50% of older women. The age-specific prevalences of cytological abnormalities are shown, while regression analysis found increasing age, increasing parity, illiteracy, and poor sexual hygiene to be risk factors for cervical dysplasia. The low level of barrier contraception means that there is little chance of preventing STDs through the use of such methods, and genital tract infection was undoubtedly exacerbated by poor sexual hygiene.

'Metastatic invasive mole' causing paraplegia.

We report a rare case of 'metastatic invasive mole' to the spinal cord causing paraplegia in a 19-year-old woman. There are no such histologically proven reports in the literature since the use of the tumour marker, beta-subunit of human chorionic gonadotrophin (beta-HCG) and chemotherapy. We stress the importance of considering this rare possibility in young woman with compressive myelopathy.

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors.

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Terminology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Differences in type, structure, quality of health care systems and availability of resources influence reporting systems. In most countries, individual systems have a long history of usage that might preclude adoption of a uniform terminology worldwide. CONSENSUS POSITION: It is desirable but unrealistic at this time to aim for a unified terminology worldwide. It should be the stated objective of the International Academy of Cytology to serve as an umbrella organization for various terminologies and enhance mutual understanding and cooperation. Translation tables of equivalent terms have been created to allow increased communication. Consensus has been achieved in defining essential elements required of any terminology system: (1) the report must be text based: numerical Papanicolaou class designations alone are inadequate; (2) an assessment of the adequacy of the sample should be included; and (3) the diagnosis must address the primary purpose of cervical cytology: to indicate the presence or absence of epithelial abnormalities. Incorporating additional elements within a terminology system may be more or less appropriate, depending on the setting in which the system is used. ONGOING ISSUES: Despite the cited problems in adopting a uniform terminology worldwide, a single system would have many advantages in terms of communication and research and may be a long-term goal worth pursuing. Countries are invited to present their individual national terminology systems and participate in an ongoing dialogue, critically evaluating the advantages and disadvantages of all systems.

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever. CONSENSUS POSITION: At our conference, the basic definitions of QA/C posed little difficulty. Presentation of the range of methods in use today and of those based on new technologies where use is proposed or has just begun also was achieved with little or no dispute. However, there was lack of consensus on exactly how QA/C methods are to be assessed. Indeed, there was little consistency in the use of different outcome measures with which we can judge success or failure of specific QA/C options. In addition, the tension between pressure to adopt sometimes uncertain or expensive method enhancements and pressure to maintain affordability and the widest possible access for populations that most need cervical cytology screening is greater than ever. ONGOING ISSUES: More data are required that would enable assessment of QA/C options with the clearest possible understanding of cost/benefits and current or new assumptions of risk. Other task forces, such as medicolegal, cost/benefit and those devoted to new technologies, are our essential partners in meeting the challenges described above.

Evaluation of visual inspection as a screening test for cervical cancer.

Visual inspection of the uterine cervix by paramedical personnel has been proposed for the early detection of cervical cancer, as an alternative to routine cytology screening in developing countries. We evaluated the performance of this procedure in detecting precursor lesions and cancer in a study involving 2843 married women in Kerala, India. Two thresholds were used to define a positive test. In the lower one, any abnormality was considered as positive. The cut-off point for the high threshold was one or more of the high-risk findings: bleeding on touch, suspicious growth/ulcer and hard, irregular, oedematous cervix. A Pap smear was performed on all subjects, and a biopsy was done for those with moderate dysplasia and above. A combination of cytology and histology findings was used as the 'gold standard'. Using the low threshold, 1279 (45%) women were positive on visual inspection, and with the higher threshold 179 (6.3%) were positive. There were six moderate dysplasias, nine severe dysplasias, ten carcinomas in situ and 13 invasive carcinomas. With the lower threshold, sensitivity and specificity to detect moderate dysplasia and above were 65.8% and 55.3% respectively; the values for severe dysplasia and above were 71.9% and 55.3% respectively and for invasive cancer were 92.3% and 55.2% respectively. With the higher threshold, the sensitivity decreased considerably (28.9% to detect moderate dysplasia lesions, 31.3% for severe dysplasia and 53.8% for clinical cancer) and the specificity increased to approximately 94%. At a lower threshold, the sensitivity was not satisfactory, and the test was highly non-specific; at a higher threshold sensitivity was even lower. Thus, the test characteristics of visual inspection are not very promising either as a preselection procedure for cytology or as a low-technology measure for cervical cancer screening in developing countries.

Significance of AgNOR count in differentiating malignant cells from reactive mesothelial cells in serous effusions.

OBJECTIVE: To distinguish reactive mesothelial cells from malignant cells in serous effusions using silver staining of nucleolar organizer regions (AgNOR) applied to ethanol-fixed cytologic preparations. STUDY DESIGN: One hundred aspirated samples of benign and malignant effusions were studied using the one-step silver staining method. Eight cytologically atypical samples were also included in the study. RESULTS: In malignant cells the mean AgNOR count was 4.72 +/- 0.76 (+/- SD), and the AgNORs were irregular in shape, while in benign mesothelial cells AgNORs were comparatively larger, single dots with a mean count of 1.92 +/- 0.23. Of the cytologically atypical samples, five were in the malignant range. The others were within benign limits. Repeat cytology of the second aspirate confirmed that finding. CONCLUSION: AgNOR study appears to be clinically useful as an additional diagnostic tool for use in ascitic and pleural fluid samples when the cytologic diagnosis is difficult.

Differential expression of jackfruit-lectin-specific glycoconjugates in metastatic adenocarcinoma and reactive mesothelial cells-a diagnostic aid in effusion cytology.

Distinguishing reactive mesothelial cells from adenocarcinoma cells in serous effusions on the basis of morphological criteria alone is often difficult. Interest has therefore been focused on identifying reliable methods to supplement the conventional cytological techniques. Plant lectins have been reported as diagnostic markers for malignant cells. We studied 51 aspirated samples of benign and malignant effusions using horseradish-peroxidase-conjugated jackfruit lectin. No significant difference was observed between the cells of pleural and peritoneal fluids. The reactively proliferated mesothelial cells of benign effusions showed a predominance of mild staining while moderate and intense staining was predominant in malignant effusions. Intense and irregular lectin binding was observed in macrophages irrespective of the cause of effusion. The lectin staining method therefore appears to have some clinical significance as an additional diagnostic aid for use in effusion cytology.

Evaluation of chemoprevention of oral cancer with Spirulina fusiformis.

The blue-green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p < 0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol or beta-carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

Argyrophilic nucleolar organizer regions in the evaluation of tumour progression in the oral mucosa: correlation with tissue pathology.

The present study has analysed the numbers of argyrophilic nucleolar organizer regions (AgNOR) in normal tissues and in premalignant and malignant lesions of the oral mucosa in order to assess their potential as a biological marker for tumour progression. On comparison of AgNOR numbers in different lesions, carcinomas showed the highest number (4.65 +/- 0.98) compared to leukoplakias (2.38 +/- 0.47) and normal tissues (1.53 +/- 0.39). Spindle cell carcinomas and poorly differentiated squamous cell carcinomas had higher AgNOR counts than well-differentiated carcinomas. In various clinically different types of oral leukoplakia, the lowest AgNOR counts were observed in homogenous leukoplakia and the highest in speckled leukoplakia. No significant difference in AgNOR number was observed between non-dysplastic and dysplastic leukoplakia, although a significant difference was evident between dysplastic leukoplakia and normal oral mucosa. Correlating the AgNOR count and tumour progression, a significantly high positive correlation coefficient (r = 0.7969, P = 0.0000) was observed.

Overall survival from breast cancer in Kerala, India, in relation to menstrual, reproductive, and clinical factors.

BACKGROUND: Breast cancer accounts for one-fourth of cancer cases seen in female patients in Kerala, India. Results of a retrospective analysis of breast cancer in Kerala are presented in this article. METHODS: Case records of 449 patients with breast carcinoma treated during 1983-1984 were reviewed. Survival analysis was done by the Kaplan-Meier product limit method. The survival curves were compared by the log-rank test. A forward stepwise procedure with the Cox proportional hazards regression analysis was performed to identify factors influencing survival. RESULTS: The overall 5-year survival rate was 40%. The 5-year survival rates were 85% for patients with T1, 63% for T2, 32% for T3, and 21% for T4 lesions. Those with N0 disease had a 68% 5-year survival rate. The survival rates were 90% for patients with Stage I, 65% for Stage II, 33% for Stage III, and 6% for Stage IV disease. On multivariate analysis, the following factors were found to significantly influence survival: response to treatment (P < 0.001), stage (P < 0.01), and regional nodal involvement (P < 0.05). CONCLUSIONS: Two-thirds of patients with advanced-stage disease on presentation seem to account for the poor overall survival. Early detection of breast cancer by breast self-examination and physician breast examination should be encouraged in developing countries to improve treatment results in breast cancer.

Role of sputum cytology in the diagnosis of mediastinal germ cell tumor.

A rare case of germ cell tumor of the mediastinum infiltrating the lung and metastasizing to the supraclavicular lymph node in a 25-year-old male is presented. The patient presented with a history of superior vena cava syndrome and chest roentgenograms revealed an abnormal mediastinum. Primary positive diagnosis was made cytologically on sputum specimens. The peculiar cell type found in the Papanicolaou stained sputum smears were correlated with fine needle aspiration cytology of lung and lymph node, and confirmed the histologic pattern of the tumor metastasizing to the lymph node. To our knowledge, the present case is the first report of a primary mediastinal seminoma (germinoma) infiltrating the lung and diagnosed by sputum cytology. These results suggest the usefulness of sputum examination as an adjunctive diagnostic procedure in the detection of patients with possible lung infiltrated germinal neoplasms.

Jack fruit lectin binding pattern in the exfoliative cytology of bronchopulmonary neoplasia.

N-acetyl D- galactosamine specific jack fruit lectin conjugate was used for the cyto-chemical study of benign and neoplastic lesions of the respiratory tract using diaminobenzidine as substrate on exfoliated cells and tissue sections. Sputum samples from patients with benign respiratory tract lesions (40), squamous cell Carcinoma (20), adenocarcinoma (16), small cell anaplastic carcinoma (12) and large cell anaplastic carcinoma (5) were used for the study. The lectin binding was strong in squamous cell carcinoma, large cell anaplastic carcinoma and adenocarcinoma, but variations in the binding pattern were observed in different carcinoma. Squamous metaplastic cells manifested slightly increased binding to lectin as compared to bronchial and native squamous epithelial cells. The nature of binding was eventually similar in cytology and histology. The ready availability and ease of preparation in purified from makes the jack fruit lectin a potential cytochemical reagent for sputum cytology.