Carcinoma In High-risk Populations Research Articles

Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis

ObjectiveThe incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening. MethodsWe searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted. ResultsWe included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56–0.96]; I2 = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13–2.61]; I2 = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78–4.58]; I2 = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37–5.54]; I2 = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77–4.06]; I2 = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%–23.67%) and most harms were of a mild to moderate severity. ConclusionThe existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.

Colorectal Carcinoma, Cyclooxygenases, and COX Inhibitors.

Colorectal carcinoma (CRC) is the most common of gastrointestinal cancers, the majority presenting with sporadic occurrence compared to the less frequently inherited syndromes. The increasing incidence, decreasing gender and age disparities, and the prevalent risk factors are concerning. The malignancy arising from benign precursor polyps transforms slowly over time. The adenoma variant polyps reported a marked upregulation of cyclooxygenases (COX), significantly COX-2 isoform, influenced by various determinants such as genetics, pathology, histology, and site of the carcinoma. These COX enzymes are responsible for prostaglandin synthesis and the consequent cascade of cell inflammation and proliferation. Therefore, COX inhibition by non-steroidal anti-inflammatory drugs (NSAIDs) targeted against both the isoforms COX-1 and COX-2 have been studied for decades in anticipation of preventing the occurrence of colorectal carcinoma in high-risk populations. This article has collated and highlighted the overexpression of COX enzymes by the adenomatous polyps and provides corroborating evidence from multiple studies in favor of COX inhibition by NSAIDs. Aspirin and Sulindac were two drugs to be initially proven to halt the progression and cause regression of the polyps. Celecoxib, a selective COX-2 inhibitor besides NSAIDs, was also used in experimental studies.

Does the Two-Tier System Accurately Predict Progression of Endometrial Hyperplasia to Endometrial Carcinoma in High-Risk Populations? A Retrospective Study in a Safety-Net Hospital

Abstract Introduction/Objective In 2014, the WHO simplified the classification of endometrial hyperplasia (EH) into a two-tier system: endometrial hyperplasia without atypia/benign endometrial hyperplasia (BEH) and atypical endometrial hyperplasia (AEH)/endometrioid intraepithelial neoplasia (EIN), as opposed to the 1994 WHO 4-tier scheme. We conducted this study to assess the diagnostic validity of the two-tier scheme in predicting upgrade to endometrioid adenocarcinoma (EA) in our high-risk patient population. Methods Retrospective review from Aug 2009 to August 2019 revealed 144 cases of EH diagnosed on biopsy. The cases were reclassified using the 2014 two-tier scheme to 81 BEH and 63 AEH. The excisional diagnoses, if available, were compared with the initial biopsy results. Results At hysterectomy, 22 AEH (50%) were diagnosed as benign, with no residual AEH, 15 cases were upgraded to EA (34.1%), and 7 had residual AEH (15.9%). Endometrial polyp was identified in 29 cases out of 63 AEH, 24 of which had a follow-up excision. Among those, 6 were upgrade to EA (25%), significantly lower than the upgrade rate of AEH without polyp (45%) (p=0.0344). Conclusion In our high-risk patient population, the likelihood of upgrade to EA at excision of a biopsy-diagnosed AEH is significantly higher than BEH and is in line with what was reported in the literature for other populations. Patients with endometrial polyps were less likely to progress to EA. Our study demonstrated the diagnostic validity of the two- tiered classification in high-risk population and supports the emphasis on cytological atypia.

The predictive value of Liver Imaging Reporting and Data System with contrast-enhanced ultrasound (v2017) in the risk of hepatocellular carcinoma in high-risk population

Objective To explore the clinical value of Liver Imaging Reporting and Data System (LI-RADS) version 2017 with contrast-enhanced ultrasound (CEUS) for the risk prediction of hepatocellular carcinoma (HCC). Methods Five hundred and seventy-one patients with HCC risk factors had received CEUS examination in Tianjin Third Central Hospital, 270 patients with 295 nodules were enrolled in this study according to the inclusion criteria. The final diagnostic reference standard was decided by surgical pathology or ultrasound-guided biopsy pathology. Each nodule was classified according to CEUS LI-RADS v2017. The diagnostic accuracy of CEUS LI-RADS v2017 for the prediction of HCC was analyzed retrospectively. Results Of all 295 nodules, 95 nodules were diagnosed by surgical pathology and 200 nodules by ultrasoud-guided biopsy pathology, among which with 245 HCC, 13 intrahepatic cholangiocarcinoma (ICC), 8 combined hepatocellular cholangiocarcinoma(CHC), 2 metastatic neoplasm of other cellular origin and 27 benign nodules.The numbers of LR-3, LR-4, LR-5 and LR-M categories were 16(5.4%), 28(9.5%), 183(62.0%), 68(23.1%) and the positive predictive value (PPV) of LR-3, LR-4 and LR-5 were 43.8%, 60.7%, 98.4% for HCC, respectively. The sensitivity, specificity and positive predictive value of LR-5 category for HCC were 73.5%, 94.0%, 98.4%, respectively. 60.3%(41/68) LR-M category nodules were pathologically confirmed to be HCC. Conclusions CEUS LI-RADS v2017 classification standard has reliable risk prediction value for patients with high risk factors of HCC, of which the LR-5 category has higher PPV for HCC. However, the differential diagnosis between HCC and other non-HCC malignancies still remains to be further studied for LR-M observations. Key words: Contrast-enhanced ultrasound; Hepatocellular carcinoma; Liver Imaging Reporting and Data System

Eosinophilic Gastroenteritis and Colitis: Not Yet Ready for the Big Leagues.

Eosinophilic Gastroenteritis and Colitis: Not Yet Ready for the Big Leagues.

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations

ObjectiveLittle evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan. MethodsUsing representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20–84 years with newly diagnosed hepatocellular carcinoma in 2000–2011 as the cases and 102,182 randomly selected subjects aged 20–84 years without hepatocellular carcinoma as the matched controls. ResultsIn subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8). ConclusionThere is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids.

LI-RADS-CEUS – proposal for a contrast-enhanced ultrasound algorithm for the diagnosis of hepatocellular carcinoma in high-risk populations

Purpose: To develop a contrast-enhanced ultrasound algorithm (LI-RADS-CEUS = Liver Imaging Reporting and Data System with contrast-enhanced ultrasound) for the diagnosis of hepatocellular carcinoma (HCC) in patients at risk.

Screening for hepatocellular carcinoma in high-risk populations

Screening for hepatocellular carcinoma (HCC) should be implemented in the high-risk population. High-risk population includes patients with cirrhosis of any etiology, patients with chronic hepatitis B virus with or without cirrhosis, and patients with chronic hepatitis C virus with cirrhosis. A randomized controlled trial of over 18,000 high-risk individuals demonstrated that biannual screening reduced HCC-related mortality by 37%. The screening test of choice is ultrasound imaging with an interval of 6months.

Developing Genetic Epidemiological Models to Predict Risk for Nasopharyngeal Carcinoma in High-Risk Population of China

To date, the only established model for assessing risk for nasopharyngeal carcinoma (NPC) relies on the sero-status of the Epstein-Barr virus (EBV). By contrast, the risk assessment models proposed here include environmental risk factors, family history of NPC, and information on genetic variants. The models were developed using epidemiological and genetic data from a large case-control study, which included 1,387 subjects with NPC and 1,459 controls of Cantonese origin. The predictive accuracy of the models were then assessed by calculating the area under the receiver-operating characteristic curves (AUC). To compare the discriminatory improvement of models with and without genetic information, we estimated the net reclassification improvement (NRI) and integrated discrimination index (IDI). Well-established environmental risk factors for NPC include consumption of salted fish and preserved vegetables and cigarette smoking (in pack years). The environmental model alone shows modest discriminatory ability (AUC = 0.68; 95% CI: 0.66, 0.70), which is only slightly increased by the addition of data on family history of NPC (AUC = 0.70; 95% CI: 0.68, 0.72). With the addition of data on genetic variants, however, our model’s discriminatory ability rises to 0.74 (95% CI: 0.72, 0.76). The improvements in NRI and IDI also suggest the potential usefulness of considering genetic variants when screening for NPC in endemic areas. If these findings are confirmed in larger cohort and population-based case-control studies, use of the new models to analyse data from NPC-endemic areas could well lead to earlier detection of NPC.

Use of ultrasound as the initial screening exam for hepatocellular carcinoma in high risk populations

Background: Detection of hepatocellular carcinoma (HCC) in high risk populations has traditionally involved the use of ultrasound (US), followed by computed tomography (CT) or magnetic resonance imaging (MRI) for confirmation of suspected lesions. The aim of our study was to determine, retrospecttively, in an unselected population of patients with cirrhosis, if an initial US could be as accurate as a subsequent CT or MRI in detecting HCC. Methods: 1600 consecutive cases from 2004-2007 in which US was performed for HCC screening were evaluated. 160 were identified which had an initial US followed by CT or MRI within 6 months. This group included 34 cases of HCC and 126 controls without HCC. Results: 26 cases of HCC were correctly identified by US, representing a sensitivity of 76.5%; the mean alpha-fetoprotein (AFP) level was 440.4 ng/dL. The other 8 cases had a false negative US; the mean AFP was 212.4 ng/dL. In 125 controls the mean AFP was 17.14 ng/dL. This group had only 12 patients, or 9.6%, with an AFP greater than 20 ng/dL, and only 1 who had an AFP greater than 400 ng/mL. In this study, the positive predictive value of US for detecting HCC was 96.3%, while the negative predictive value was 94.0%. Combining US with the AFP level, and using a cutoff of 20 ng/dL, the sensitivity was increased to 87.5%. In this series of 160 patients, only 2 patients with HCC had a negative US and normal serum AFP. Conclusion: In combination with regular monitoring of AFP levels, US can eliminate more expensive imaging studies until further investigation by CT or MRI of questionable US results or elevated AFP is necessary, thus reducing the overall cost of monitoring these populations.

S1278 Use of Ultrasound as the Initial Imaging Exam for Hepatocellular Carcinoma in High Risk Populations

S1278 Use of Ultrasound as the Initial Imaging Exam for Hepatocellular Carcinoma in High Risk Populations

Antibodies to gp350/220 Enhance the Ability of Epstein-Barr Virus To Infect Epithelial Cells

Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma. We report here that antibodies to gp350/220, which inhibit EBV infection of B cells, enhance infection of epithelial cells. The effect is not mediated by Fc receptor binding but is further enhanced by antibody cross-linking, which may patch gp350/220 in the virus envelope. Saliva from EBV-seropositive individuals has similar effects that can be reversed by depletion of antibody. The results are consistent with a model in which gp350/220 interferes with the access of other important players to the epithelial cell surface. The results may have implications for the development of nasopharyngeal carcinoma in high-risk populations in which elevated titers of antibody to EBV lytic cycle proteins are prognostic.

Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies

Objective. To study the pattern of protein expression associated with a predisposition to develop ovarian cancer. Methods. Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE). Results. Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction. Conclusions. Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk.

Detection and localization of early lung cancer by fluorescence bronchoscopy

BACKGROUND Curative therapy is available for patients with Stage 0 lung carcinoma, with a >90% 5-year survival rate. Promising chemopreventive agents also are under investigation currently to reduce the risk of lung carcinoma in high risk populations. However, preinvasive bronchial lesions (moderate to severe dysplasia and carcinoma in situ) are very small and thin. They are difficult to localize by conventional white-light bronchoscopy. Fluorescence bronchoscopy is a new diagnostic tool for the detection of these preinvasive lesions. METHODS The data on the use of fluorescence bronchoscopy to detect and localize preinvasive lesions in current heavy smokers and in former smokers at the British Columbia Cancer Agency as well as the worldwide experience cited in MEDLINE, Index Medicus, and Deutsches Institut fur Medizinische Dokumentation und Information (Cologne, Germany) comparing white-light and fluorescence bronchoscopy using the lung imaging fluorescence endoscope (LIFE)-Lung device (Xillix Technologies Corp., Richmond, British Columbia, Canada) were reviewed. RESULTS Among current heavy smokers and former smokers with sputum atypia, the prevalence of carcinoma in situ was 1.6%. Moderate or severe dysplasia was found in another 19%. The preinvasive lesions were found to be small: 55% measured ≤1.5 mm in greatest dimension. Over 1000 cases have been reported in the literature between 1994 and 1999. Overall, 40% of the preinvasive lesions were detected by white-light bronchoscopy alone. The addition of fluorescence bronchoscopy increased the detection rate to an average of 80%. CONCLUSIONS Preinvasive lesions, especially dysplastic lesions, are small. They are difficult to detect and localize by white-light bronchoscopy. Fluorescence bronchoscopy improves the detection rate. It is an important part of the armamentarium in the overall management of early lung cancer. Cancer 2000;89:2468–73. © 2000 American Cancer Society.

Lung cancer screening results in the National Cancer Institute New York Study

BACKGROUND Anecdotal reports of radiologically occult early stage lung carcinomas detected by sputum cytology suggested that screening by cytology might lead to earlier diagnosis, more effective surgical therapy, and lower death rates from lung carcinoma. Thus, a randomized study was undertaken to evaluate sputum cytology as a lung carcinoma screening technique supplementing the chest X-ray. METHODS Three major medical centers participated in the study, recruiting approximately 10,000 cigarette smoking men older than 45 years of age at each center: Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, NY, Johns Hopkins Hospital in Baltimore, MD, and The Mayo Clinic in Rochester, MN. At MSKCC, the men were divided randomly into two groups: a dual screen group received four monthly sputum cytology examinations in addition to annual posteroanterior and lateral chest X-rays and an X-ray only group received annual chest X-rays but no sputum examinations. The men suspected of lung carcinoma because of radiologic or sputum cytology findings were referred immediately for evaluation, and those with operable lung carcinoma were recommended for surgery and treated with intent to cure. RESULTS The men who entered into the study remained in the screening program for 5–8 years, depending on their date of enrollment, and were followed for 2 years after screening. Follow-up was completed on more than 99%. There were 53 of the 10,040 men in the study who were found to have lung carcinoma on initial examination (prevalence): 23 were in the X-ray only group; of 30 found in the dual screen group, 9 (all with squamous cell carcinoma) were detected by cytology alone. During the entire study and the 2-year follow-up period, 354 of the 10,040 men developed lung carcinoma, equally divided between the dual screen and X-ray only groups. Nearly two-thirds (190 men) had lesions that were detected by screening, and over 50% (100 men) were in Stage I. Excluding oat cell carcinoma, during the screening period 175 of 250 carcinomas (70%) were detected by screening. In contrast, during the 2-year post-screening period, 61 lung carcinomas were diagnosed of which only 12 (20%) were Stage I. Chest X-ray was most effective in detecting peripheral adenocarcinomas of the lung, which were the most common cell type. Cytology was most effective in detecting early epidermoid carcinomas of major bronchi. The epidermoid carcinomas grew slowly, metastasized late, and after becoming visible by X-ray could be treated equally effectively as in the earlier occult stage. Forty percent of all the lung carcinomas were detected in Stage I, and at least two-thirds of the patients with Stage I lung carcinoma treated by complete resection did not die of their disease. Overall 5-year survival of all patients with lung carcinoma who had enrolled in the detection program was 35%, compared with 13% for the United States as a whole during this same time period. CONCLUSIONS Sputum cytology and the chest X-ray complemented each other as lung carcinoma detection techniques. The chest X-ray best detected peripheral adenocarcinomas of the lung, which are the most common type of lung carcinoma. Sputum cytology detected epidermoid carcinomas arising in major bronchi, but these are slow growing tumors that can be resected and cured after becoming visible by chest X-ray. Thus, for subjects at risk of lung carcinoma who could be followed by annual chest X-rays, sputum cytology did not improve survival, but for high risk subjects who had only a single screening examination, sputum cytology increased the number of early lung carcinomas detected. The design of the current study did not permit evaluation of chest X-ray screening versus nonscreening for prevention of death from lung carcinoma. However, the large proportion of Stage I lung carcinomas and the high survival rate of patients in this study compared with Surveillance, Epidemiology, and End Results program data strongly suggested that screening for lung carcinoma in high risk populations is a valuable public health measure. Cancer 2000;89:2356–62. © 2000 American Cancer Society.

Detection and localization of early lung cancer by fluorescence bronchoscopy.

Curative therapy is available for patients with Stage 0 lung carcinoma, with a >90% 5-year survival rate. Promising chemopreventive agents also are under investigation currently to reduce the risk of lung carcinoma in high risk populations. However, preinvasive bronchial lesions (moderate to severe dysplasia and carcinoma in situ) are very small and thin. They are difficult to localize by conventional white-light bronchoscopy. Fluorescence bronchoscopy is a new diagnostic tool for the detection of these preinvasive lesions. The data on the use of fluorescence bronchoscopy to detect and localize preinvasive lesions in current heavy smokers and in former smokers at the British Columbia Cancer Agency as well as the worldwide experience cited in MEDLINE, Index Medicus, and Deutsches Institut fur Medizinische Dokumentation und Information (Cologne, Germany) comparing white-light and fluorescence bronchoscopy using the lung imaging fluorescence endoscope (LIFE)-Lung device (Xillix Technologies Corp., Richmond, British Columbia, Canada) were reviewed. Among current heavy smokers and former smokers with sputum atypia, the prevalence of carcinoma in situ was 1.6%. Moderate or severe dysplasia was found in another 19%. The preinvasive lesions were found to be small: 55% measured < or = 1.5 mm in greatest dimension. Over 1000 cases have been reported in the literature between 1994 and 1999. Overall, 40% of the preinvasive lesions were detected by white-light bronchoscopy alone. The addition of fluorescence bronchoscopy increased the detection rate to an average of 80%. Preinvasive lesions, especially dysplastic lesions, are small. They are difficult to detect and localize by white-light bronchoscopy. Fluorescence bronchoscopy improves the detection rate. It is an important part of the armamentarium in the overall management of early lung cancer.

Diagnosis of early oral and oropharyngeal squamous carcinoma: obstacles and their amelioration.

These comments and observations are based on 25 years of clinical practice in oncology, and prospective research studies of oropharyngeal squamous carcinoma in high-risk populations; the review of innumerable publications related to squamous carcinoma (most of which have usually been based on retrospective analysis of data or anecdotal information) and my observations, as a clinician and a patient, of the behavior, beliefs, and practice of dental and medical clinicians. Although the oral cavity and oropharynx are as easily accessible for visualization, as is skin, and the population at high risk (development of squamous cancers of these sites has been identi®ed in a multitude of studies in the USA and Western Europe), early diagnosis has not been forthcoming with the resultant lack of increase in 5-year survival rates when compared to cancers of other sites. It is with dismay I observe that over the last 20±30 years, early diagnosis and survival rates for cancers of the breast, colon, prostate and melanoma have increased considerably, due primarily to an increase in early detection. However, survival rates for cancers of the oral cavity and oropharynx have remained constant during this period at approximately 40±50% with a small decrease in the black population. Paradoxically, even though the mucosa of the colon is internal and requires endocscopic examination for evaluation, 36% of colon cancers (US) are localized when diagnosed, identical to the number of localized oral/ oropharyngeal (O/OP) cancers diagnosed. Most of the O/OP cancers at time of diagnosis are symptomatic late-stage disease with at least 50% revealing regional cervical metastases. Survival is poor. We have an overwhelming responsibility to ameliorate this situation. I believe there are two areas of concern that are greatly responsible for this de®ciency in diagnosis. The ®rst deals with the split professional responsibility attendant to this anatomical region. Dentists who are, supposedly, in the ®rst line of defense and are responsible for the early diagnosis of these cancers have a con icted position. Their training, education, and experience in dealing with cancer as a concept and in practical terms is somewhat limited. The emphasis in their education and practice is primarily related to restoration and amelioration of dental and hard tissue problems. Although at home in the oral cavity and much more capable of performing a soft tissue examination than their physician counterparts, they re exly respond to the restoration mode. My experience as a patient, clinician, teacher and casual observer con®rms that few generalists or specialists evaluate the high-risk sites of occurrence as part of the standard dental examination. Literature disseminated by major dental organizations, government, non-pro®t, dental schools, etc., list programs and lectures in a variety of dental spheres. Cancer infrequently is listed as a topic. The physician, on the other hand, although trained to be concerned with oncology, has minimal or no training in the oral cavity. Sections of O/OP cancer and examination of this anatomical region in medical texts are woefully inadequate. Related lectures for medical students and trainees are few. A physician using a tongue blade with a pen ashlight for illumination, requesting the patient to say ``ah'', cannot possibly highlight the minimal mucosal changes which signify early asymptomatic squamous cancer. Among medical practitioners

Two-site enzyme immunoassay for alpha-fetoprotein in dried-blood samples collected on filter paper.

This is a method for measuring alpha-fetoprotein (AFP) in eluates of dried-blood samples on filter paper by use of a simple, sensitive two-site enzyme immunoassay. The spot, 6 mm in diameter (equivalent to about 12 microL of whole blood), is incubated overnight with alkaline phosphatase conjugated to rabbit anti-AFP antibody in a tube containing a polystyrene bead coated with mouse monoclonal antibody to AFP. After the beads are washed the enzyme activities associated with them are determined colorimetrically, with p-nitrophenyl phosphate as substrate. The measurable range of AFP is from 9 to 900 micrograms per liter of plasma. AFP in the dried-blood spot as determined by this method correlated well with the AFP value for serum from the same blood sample as determined by radioimmunoassay (r = 0.957, p less than 0.001). Preliminary studies in which we used this method with 242 healthy blood donors and 60 patients with hepatocellular carcinoma indicate that it may be suitable for use in mass screening for hepatocellular carcinoma in high-risk populations.

Pathology of colorectal adenomas: a colonoscopic survey.

The size, histological type, and grade of dysplasia of a large series of colorectal adenomas removed by colonoscopic polypectomy were matched against other variables such as anatomical site, age, sex, and number of adenomas per patients. Special emphasis was placed on the criteria for grading dysplasia in adenomas and the possible significance of severe dysplasia as a selective marker for increased colorectal cancer risk. The results showed that small adenomas (mostly with mild dysplasia) were evenly distributed throughout the colorectum but that adenomas showing severe dysplasia (mostly the larger tumours, greater than 10 mm diameter) were concentrated in the left colon and rectum, particularly the sigmoid part which is also the segment with the highest risk of colorectal carcinoma in high risk populations. Severe dysplasia in adenomas appears to be a selective histopathological marker for increased colorectal cancer risk. It is closely linked with increasing age and numbers of adenomas per patient, with the large adenomas and particularly those with a villous component in their histology. Severe dysplasia and multiple adenomas could be valuable markers for selecting from the total adenoma population those most deserving of close surveillance in follow-up cancer prevention programmes. Conceptually it would appear advantageous to think in term of the dysplasia-carcinoma sequence in the colorectum rather than the polyp-cancer or adenoma-carcinoma sequence. The implications of these results in the study of the aetiology of colorectal cancer are discussed.