Clinical evaluation of an autofluorescence diagnostic device for oral cancer detection: a prospective randomized diagnostic study

The prognosis for patients with oral squamous cell carcinoma remains poor despite advances in multimodal treatment concepts. Early diagnosis and treatment is the key to improved patient survival. A device (VELscope) that uses autofluorescence technology, allowing direct fluorescence visualization of the oral cavity, might be a useful tool for oral cancer detection or as an adjunct to standard clinical examination. A total of 289 patients with oral premalignant lesions were randomly divided into two groups for clinical examination of precancerous oral lesions. In group 1, 166 patients were examined conventionally with white light, and in group 2, 123 patients were examined with the autofluorescence visualization device (VELscope) in addition to the white light examination. Biopsies were obtained from all suspicious areas identified in both examination groups (n=52). In the first step, baseline characteristics of the two groups (only white light vs. white light and VELscope) were compared to exclude selection bias. In the second step, for the group examined with white light and VELscope (123 patients), the diagnostic strategies were compared with regard to sensitivity and specificity using biopsy as the gold standard. The results showed that using the VELscope leads to higher sensitivity (100% instead of 17%), but to lower specificity (74% instead of 97%). Thus, we can conclude that the VELscope is a useful new diagnostic device for detection of oral cancer diseases.     

The effectiveness of community-based visual screening and utility of adjunctive diagnostic aids in the early detection of oral cancer

A systematic review of community-based oral cancer screening programmes published between 1966 and March 2002 was undertaken. Data relating to study design, sampling and characteristics of the study group, interventions, and reported outcomes and diagnostic value of visual screening or adjunctive diagnostic aids were abstracted from 36 articles meeting inclusion and exclusion criteria. From these reports, there is insufficient evidence to demonstrate the effectiveness of community-based oral cancer visual screening in enhancing the early detection of oral cancer, due to small effect size. While the evidence is fair to support use of toluidine blue as an aid in diagnosis of oral cancer, there is insufficient evidence to determine whether the use of this or other adjunctive techniques will increase the detection of oral malignancies in community screening programmes. Targeted clinical examination of high-risk individuals may be more effective than mass screening in facilitating early detection of oral cancers.     

The value of diagnostic aids in detecting pancreas cancer

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a "correct" diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 76Selenomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonography gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangiopancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (greater than 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non-cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se-methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.     

Annual screening for oral cancer detection

Most oral cancer and oral mucosal screening programs initiated in the past 20 years have been limited to a single examination of the population under study. Age specific, annual oral mucosal screening examination as a part of general health screening has been in operation in Tokonama city, Japan, from 1986. From 1996 the same target population aged 40 years and older has been invited for screening. The program coverage extended to 26% of the city population. During 1995-1998, out of 9536 attendees who participated in a general health and oral mucosal screening program in Tokoname city 6340 subjects (66.5%) re-attended at least for one further screening examination. There was no difference in the attendance for two annual mucosal examinations between male (67.0%) and female (66.2%) subjects. Three thousand nine hundred thirty-five subjects attended oral screening all 3 years (1996-1999) and the overall show-up rate for three consecutive examinations was 61%. During September-October 1996, 42 volunteer dentists carried out 6705 mouth examinations among those aged 40 years and older at the Municipal Center. One oral cancer was detected in 1996, in a subject free of any mucosal disease in the previous year. Among the screen-negative cases in 1996, 78% re-attended for screening in 1997 and 79% re-attended in the subsequent year. In the cohort that re-attended screening (1996-1998), oral mucosal pathology detected in three consecutive screenings included 18 leukoplakias, 24 with oral lichen planus and 343 other benign mucosal lesions. The number of subjects who complied to return and who remained disease-free over the 3-year period amounted to 3860, 59% of the disease-free subjects seen in 1996. A regular smoker was less likely to attend oral cancer screening in the three consecutive years of follow-up (odds ratio: 0.832, 95% CI 0.701-0.988). Satisfactory participation can be obtained for annual oral mucosal screening in Japan: this allows detection of new lesions, including oral cancer and leukoplakia (a surrogate marker of cancer risk). The number of new oral cancers detected in the program was too low to determine the optimal frequency for oral cancer screening but new oral leukoplakias were found on annual re-screening: the data indicate that the interval between two screens for this population should not be greater than 12 months.     

New diagnostic techniques for breast cancer detection

Breast imaging has made huge advances in the last decade, and along with newer techniques to diagnose primary breast cancer, many novel methods are being used and look promising in detecting distant metastasis, recurrent disease and assessing response to treatment. Full-field digital mammography optimizes the lesion-background contrast and gives better sensitivity, and it is possible to see through the dense tissues by altering computer windows; this may be particularly useful in younger women with dense breasts. The need for repeat imaging is reduced, with the added advantage of reduced radiation dose to patients. Computer-aided detection systems may help the radiologist in interpretation of both conventional and digital mammograms. MRI has a role in screening women at high risk for breast cancer. It also aids in cancer management by assessing response to treatment and can help in deciding appropriate surgery by providing accurate information on the extent of the tumor. Newer diagnostic techniques such as sestamibi scans, optical imaging and molecular diagnostic techniques look promising, but need more investigation into their use. Their roles will appear clearer in coming years, and they may prove to be of help in further investigating lesions that are indeterminate on standard imaging. Other upcoming techniques are contrast-enhanced mammography and tomosynthesis. These may give additional information in indeterminate lesions, and when used in screening they aid in reducing recall rates, as shown in recent studies. PET/computed tomography has a role in detecting local disease recurrence and distant metastasis in breast cancer patients.     

An educational program for oral cancer detection

The Virginia oral cancer screening program provides a unique educational opportunity for undergraduate dental and medical students to enhance their skills in oral diagnosis and biopsy technique. During this week-long trip to underserved areas of the state, an average of 761 patients are examined and 44 biopsies performed. Approximately 31% of all the biopsies done since 1972 have been diagnosed as either a premalignant or malignant lesion. The value of this program to both the students and the patients is discussed.     

Noninvasive diagnostic modalities for early detection of colorectal cancer

Colorectal cancer (CRC) screening strategies currently approved are colonoscopy every 10 years, annual fecal occult blood testing (FOBT), flexible sigmoidoscopy every 5 years, annual FOBT plus flexible sigmoidoscopy, and double-contrast barium enema every 5 years. Colonoscopy has been shown to be preferable, but it is invasive, needs bowel preparation, entails a risk of perforation, and is highly operator-dependent. Several noninvasive strategies are being developed as alternatives to colonoscopy. CT colonography (CTC), also known as virtual colonoscopy, has widely variable results but has been shown to have acceptable cost-effectiveness at either 5-year or 10-year intervals, whether it is performed using two-dimensional or three-dimensional techniques. Fecal immunochemical tests have now been shown to have clearly superior performance compared with guaiac-based testing and may become the FOBT of choice. Stool DNA (sDNA) testing has been improved by the addition to the commercial assay of gel-based DNA capture and buffering solutions for DNA stabilization. Simplified sDNA assays (for vimentin methylation and long DNA only) may also improve sensitivity. Advances in our understanding of the molecular genetic changes involved in neoplastic transformation have led to new noninvasive methods to detect tumors. The future of CRC screening will be driven by the performance characteristics of these technologies, which will be more clearly understood as additional data emerge.     

COVID-19 and oral cancer: Critical viewpoint

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has marked the beginning of a new pandemic named coronavirus disease 2019 (COVID-19). The World Health Organization has announced it as a health emergency that is of international concern. The disease has been reported to cause respiratory illness, pneumonia and even hinder the immunity of an individual. Individuals with disturbed immune responses have been found to be quite susceptible to this viral infection. Oral cancer patients are also at high risk in this pandemic situation and might encounter severe detrimental outcomes. Angiotensin receptors, documented in studies as the path of entry of this virus, are highly expressed in the epithelial cells of oral mucosa, making the group of individuals with oral cancers even more vulnerable. Extracellular matrix metalloproteinase inducer is another potential target for SARS-CoV-2. An exhaustion of angiotensin converting enzyme 2 cell receptors leads to protumoral effects, whereas a downregulation of extracellular matrix metalloproteinase inducer leads to antitumoral effects. Thus, it causes a variation of the biological behavior of the tumor. This article focusses on the molecular mechanisms, effects and patho-physiology of COVID-19 in oral squamous cell carcinoma patients. The different molecular changes in oral squamous cell carcinoma in the background of COVID-19 will modify various environmental factors for this pathology and have an effect on the carcinogenesis process. Understanding the behavior of the tumor will help plan advanced treatment strategies for oral squamous cell carcinoma patients in the background of COVID-19.     

Cell electrophoresis for diagnostic purposes. II. Critical evaluation of conventional cytopherometry.

Determination of the electrophoretic mobility of test cells has been widely used in an attempt to detect so-called lymphokines in a laboratory test for cancer, but operational difficulties are inherent in conventional cytopherometers. This study therefore investigates the technical and operational aspects of cell electrophoresis, using the Zeiss cytopherometer; e.g. influence of electro-osmosis, focus uncertainty, movement due to convection and other sources of error. Implications and possible improvements in the test are discussed.     

Patient decision aids for cancer treatment

BACKGROUND:

Although patient decision aids (pDAs) are effective, widespread use of pDAs for cancer treatment has not been achieved. The objectives of this study were to perform a systematic review to identify alternate types of decision support interventions (DSIs) for cancer treatment and a meta‐analysis to compare the effectiveness of these DSIs to pDAs.

METHODS:

The inclusion criteria for the study were: 1) all published studies using a randomized, controlled trial design, and 2) DSIs involving treatment decision‐making for breast, prostate, colorectal, and/or lung cancer. For this analysis, DSIs were classified as pDAs if: 1) one reported outcome measure mapped onto the International Patient Decision Aids Standards Collaboration effectiveness criterion, and 2) the DSI was evaluated relative to standard consultation. Random effects models were used to compare the effectiveness of pDAs relative to other identified DSIs for reported outcomes.

RESULTS:

A total of 71 studies were reviewed, and 24 met the inclusion criteria. Overall, there were no significant differences in knowledge, satisfaction, anxiety, or decisional conflict scores between pDAs and other DSIs.

CONCLUSIONS:

This study showed that the effectiveness of other DSIs, including question prompt lists and audiorecording of the consultation, is similar to pDAs. This is important because it may be that these less complex DSIs may be all that is necessary to achieve similar outcomes as pDAs for cancer treatment. Cancer 2013. © 2012 American Cancer Society.     

Decision aids for breast cancer chemoprevention

The article by Korfage and colleagues in this issue of Breast Cancer Research highlights the importance of enabling women to make informed choices about breast cancer chemoprevention. Decision aids have the potential to improve knowledge and decision-making in this context, but they do not guarantee increased uptake of chemoprevention amongst high-risk women if this option is inconsistent with women’s values. Important avenues for further research in this area include evaluating: decision aids with explicit values clarification exercises and with comparison between chemoprevention and nonpharmacological options to reduce breast cancer risk, the influence of mediating factors such as anxiety and risk perception, and the role of clinicians and family members in decision-making.The article by Korfage and colleagues in this issue of Breast Cancer Research investigates the efficacy of an online decision aid for improving informed decision-making about breast cancer chemoprevention amongst women with increased risk of developing breast cancer [1]. This study combines two areas of high interest in the research literature: the potential of chemoprevention to reduce the burden of cancer [2], and the use of decision aids to improve patient knowledge and decision-making in the prevention setting [3,4].The efficacy of chemoprevention for breast cancer prevention is well established, and recently updated clinical guidelines recommend discussing several chemoprevention options with women at increased breast cancer risk: tamoxifen, raloxifene and exemestane [2]. However, a review of breast cancer chemoprevention decision-making indicates that interest amongst high-risk women is low: 25% on intention measures and 15% for actual uptake, reflecting a perception that the benefits do not outweigh the harms for many women [5]. This sensitivity to individual preferences makes it an ideal setting for decision support interventions. Decision aids are nondirective, unbiased tools that provide patients with evidence-based information about their medical options and expected outcomes, in clear, verbal and visual formats [4]. They help patients to understand their available options, and weigh up the pros and cons of each option in light of their own values, in order to make an informed decision. Systematic reviews have shown that decision aids improve knowledge of medical options and outcomes, enable more realistic expectations, reduce decisional conflict, and increase active participation in screening and treatment decisions, including the cancer setting [3,4].The majority of studies on decision-making in the breast cancer chemoprevention context have been based on hypothetical scenarios, which may not predict actual uptake, and there is a need for more research on the quality and underlying mechanisms of decision-making [5]. In the article that accompanies this editorial, Korfage and colleagues contribute new evidence to this field by examining both intention and uptake decision 3 months later, in relation to sufficient knowledge and consistent attitudes towards chemoprevention [1]. They demonstrate a novel way to measure whether the decision was informed or not, based on the Multidimensional Measure of Informed Choice [6]. Deciding to take chemoprevention with a positive attitude, deciding against chemoprevention with a negative attitude, or remaining undecided with a neutral attitude towards chemoprevention were all considered informed decisions, if women demonstrated sufficient knowledge regarding potential benefits and risks.While further research is needed to establish the validity of this dichotomous outcome in comparison with more established measures, the authors’ conceptualisation of informed choice highlights an important distinction between the prevention and treatment setting. That is, remaining undecided may be considered rational when there is sufficient knowledge but ambivalent attitudes towards a preventive option, since this context is not as time sensitive as a treatment decision. Korfage and colleagues'' results suggest that the decision aid improved informed choice at the intention stage but not at 3-month follow-up, at which point informed choice was low across both intervention and control groups due to decreased knowledge [1]. Analysis of mediating factors in future research may shed more light on the issue of knowledge retention. Two factors suggested by previous research are: breast cancer-related anxiety, which has been shown to motivate intention but also impair the processing of information [7]; and the difference between estimated and perceived risk, which may help to explain why women are ambivalent towards the use of chemoprevention despite evidence of its efficacy in reducing risk [5].The negative attitudes towards chemoprevention found in this study are common to many other diseases for which medication would be effective [8], and it is important to note that the use of decision aids will not increase uptake of chemoprevention if this option is simply inconsistent with most women’s values regarding the relative benefits and harms. Decision aids do have the potential to improve informed choices about breast cancer chemoprevention [3,4], but since 45% of women who received this decision aid remained undecided after 3 months [1] additional decisional support may be needed in this context. Decision aids with explicit value clarification exercises, designed to help patients clarify how important the potential benefits and harms are to them, have been shown to improve informed choice [4,9]. Comparison of chemoprevention with nonpharmacological options to reduce breast cancer risk, including surgical and lifestyle options, could also be an important addition to decision aids to help women make a decision based on knowledge of all the available options.From a broader perspective, women commonly seek information about breast cancer online, in response to regular awareness campaigns [10] and less predictable media coverage of celebrity experiences [11], such as the recent case of Angelina Jolie’s preventive double mastectomy to reduce her high risk of breast cancer [12]. Having evidence-based information and decision support tools readily available and promoted in the public domain is therefore important. The online decision aid format demonstrated by Korfage and colleagues also allows the information to be tailored to an individual’s known risk factors [1].Decision aids can also play a role in improving communication with clinicians and family members, who are important sources of both information and values [13] and may have a strong influence on women’s choices about chemoprevention [14,15]. Indeed, preliminary research indicates that decision aids can have a positive effect on doctor–patient communication [5]. Further research in this area should recognise the need for doctor–patient–family partnership, and mediating factors known to influence decision-making, to help women make fully informed choices about breast cancer chemoprevention.

Competing interests

The authors declare that they have no competing interests.     

ROC曲线评价CEA、CYFRA21-1对非小细胞肺癌的诊断价值

目的:应用ROC曲线评价CEA、CYFRA21-1对局部晚期非小细胞肺癌(NSCLC)诊断的价值。方法:采用电化学发光法测定局部晚期非小细胞肺癌组、良性肺病组、正常对照组血清CEA、CYFRA21-1表达水平。应用ROC曲线对各指标的诊断效能进行分析和评价。结果:局部晚期非小细胞肺癌患者血清CEA和CYFRA21-1的浓度明显高于良性肺病组和健康体检组(P<0.05);局部晚期非小细胞肺癌患者血清CEA和CYFRA21-1的敏感性均明显高于良性肺病组和健康体检组(P<0.05)。二者联合检测的敏感性为74.11%,明显高于单项检测。CEA、CYFRA21-1的ROC曲线下面积分别为0.848、0.878。结论:CEA、CY-FRA21-1对非小细胞肺癌的诊断有一定的临床价值。二者联合可提高检测的敏感性。