Cancer Screening and Early Detection

Breast Cancer Screening

France

Li CF, Yan ZK, Chen LB, et al.
Desmin detection by facile prepared carbon quantum dots for early screening of colorectal cancer.
Medicine (Baltimore). 2017; 96(5):e5521 [PubMed] Free Access to Full Article Related Publications

Th aim of this study was to develop a new facile chemical method for early screening of colorectal cancer.The -C(O)OH groups modified Carbon Quantum Dots (CQDs) were prepared by an facile innovative route of acid attacking on carbon nanotubes (CNTs). The -C(O)OH groups were further transported into -C(O)Cl groups by SOCl2 treating. The obtained ClCQDs were conjugated onto the anti-Desmin, which were applied for testing the Desmin concentration in serum by using linearly fitted relationship with photoluminescence (PL) intensity.The obtained carbon quantum dots are quasispherical graphite nanocrystals with photoluminescence at about 455 nm. The Desmin with concentration of 1 ng/mL can lead to a decrease of PL intensity for anti-Desmin conjugated CQDs with good linearity. This assay had good specificity for Desmin with in interferential substances of immunoglobulin G (IgG), alpha fetoprotein (AFP), and carcinoembryoic antigen (CEA).A new facile acid attack method was developed to prepare ClCQDs, which could conjugate onto the anti-Desmin for detection of Desmin in serum with high sensitivity and specificity. As the detection limit is lower than 1 ng/ mL, this work provides a promising strategy for the evaluation of colorectal cancer risk with low cost and excellent sensing performance.

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Park YM, Kim HS, Park JJ, et al.
A simple scoring model for advanced colorectal neoplasm in asymptomatic subjects aged 40-49 years.
BMC Gastroenterol. 2017; 17(1):7 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Limited data are available for advanced colorectal neoplasm in asymptomatic individuals aged 40-49 years. We aimed to identify risk factors and develop a simple prediction model for advanced colorectal neoplasm in these persons.
METHODS: Clinical data were collected on 2781 asymptomatic subjects aged 40-49 years who underwent colonoscopy for routine health examination. Subjects were randomly allocated to a development or validation set. Logistic regression analysis was used to determine predictors of advanced colorectal neoplasm.
RESULTS: The prevalence of overall and advanced colorectal neoplasm was 20.2 and 2.5% respectively. Older age (45-49 years), male sex, positive serology of Helicobacter pylori, and high triglyceride and low high-density lipoprotein (HDL) levels were independently associated with an increased risk of advanced colorectal neoplasm. BMI (body mass index) was not significant in multivariable analysis. We developed a simple scoring model for advanced colorectal neoplasm (range 0-9). A cutoff of ≥4 defined 43% of subjects as high risk for advanced colorectal neoplasm (sensitivity, 79%; specificity, 58%; area under the receiver operating curve = 0.72) in the validation datasets.
CONCLUSION: Older age (45-49 years), male sex, positive serology of H. pylori, high triglyceride level, and low HDL level were identified as independent risk factors for advanced colorectal neoplasm.

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Feng X, Tan X, Alenzi EO, et al.
Spatial and temporal variations of screening for breast and colorectal cancer in the United States, 2008 to 2012.
Medicine (Baltimore). 2016; 95(51):e5656 [PubMed] Free Access to Full Article Related Publications

Cancer screening tests are important tools to combat cancer-related morbidity and mortality. There is limited up-to-date research on spatial and temporal variations of colorectal and breast cancer screening in the United States.County-level data of cancer screening adherence rates were generated from 2008 to 2012 Behavioral Risk Factor Surveillance System. We performed the univariate local indicators for spatial analyses (LISA) for the geographic differences of screening adherence rate and the differential LISA for the change of screening adherence rate from 2008 to 2012.In the univariate LISA, low-to-low clusters were consistently identified in counties of New Mexico, Wyoming, and Mississippi (P < 0.05) for both screenings. In the differential LISA, we found low-to-low clusters in Indiana counties (P < 0.05) for mammography screening, which implied that counties with a below-average difference in mammography adherence were surrounded by counties of below-average difference in adherence rates. A high-to-high cluster was also identified in the southern Appalachian counties for mammography screening (P < 0.05). No obvious spatial pattern was found for the colorectal cancer screening adherence rate across the United States.We found low-to-low clusters over time in adherence to screening guidelines for both cancer types in New Mexico, Wyoming, and Mississippi, and clusters of potential decrease in adherence to mammography screening guideline in counties of Indiana. The study also showed improvement on mammography screening clustered in southern Appalachia. The methodology adopted in this study identified areas with clusters of consistent low adherence to screening and a decrease in adherence, which implies that further research and intervention is warranted.

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USA

Attena F, Cancellieri M, Pelullo CP
Scarce information about breast cancer screening: An Italian websites analysis.
Medicine (Baltimore). 2016; 95(50):e5615 [PubMed] Free Access to Full Article Related Publications

Although the public should have complete and correct information about risk/benefit ratio of breast cancer screening, public knowledge appears generally scarce and oriented to overestimate benefits, with little awareness of possible disadvantages of the screening.We evaluated any document specifically addressed to the general female public and posted on internet by Italian public health services. The presence of false positive, false positive after biopsy, false negative, interval cancer, overdiagnosis, lead-time bias, exposure to irradiation, and mortality reduction was analyzed.Of the 255 websites consulted, 136 (53.3%) had sites addressed to the female public. The most commonly reported information points were the false-positive (30.8% of sites) and radiation exposure (29.4%) rates. Only 11 documents mentioned overdiagnosis, 2 mentioned risk of false positive with biopsy, and only 1 mentioned lead-time bias. Moreover, only 15 sites (11.0%) reported quantitative data for any risk variables.Most documents about breast cancer screening published on the web for the female public contained little or no information about risk/benefit ratio and were biased in favor of screening.

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Overbeek KA, Cahen DL, Canto MI, Bruno MJ
Surveillance for neoplasia in the pancreas.
Best Pract Res Clin Gastroenterol. 2016; 30(6):971-986 [PubMed] Related Publications

Despite its low incidence in the general population, pancreatic cancer is one of the leading causes of cancer-related mortality. Survival greatly depends on operability, but most patients present with unresectable disease. Therefore, there is great interest in the early detection of pancreatic cancer and its precursor lesions by surveillance. Worldwide, several programs have been initiated for individuals at high risk for pancreatic cancer. Their first results suggest that surveillance in high-risk individuals is feasible, but their effectiveness in decreasing mortality remains to be proven. This review will discuss which individuals are eligible for surveillance, which lesions are aimed to be detected, and which surveillance modalities are being used in current clinical practice. Furthermore, it addresses the management of abnormalities found during surveillance and topics for future research.

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Krishnamurthy S, Bevers T, Kuerer HM, et al.
Paradigm Shifts in Breast Care Delivery: Impact of Imaging in a Multidisciplinary Environment.
AJR Am J Roentgenol. 2017; 208(2):248-255 [PubMed] Related Publications

OBJECTIVE: The practice of breast imaging in a collaborative multidisciplinary environment adds significant value to outcomes in women's health care. In this article, we describe multidisciplinary considerations in breast cancer screening and early detection, the impact of imaging and histopathologic findings in the diagnostic evaluation and management of breast abnormalities, and the contribution of imaging to surgical and radiation therapy planning for the breast cancer patient.
CONCLUSION: The multidisciplinary delivery of breast care for women that incorporates screening, diagnosis of borderline and high-risk lesions, and management of the breast cancer patient adds considerable value to outcomes in health care.

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Abdul-Razak M, Chung H, Wong E, et al.
Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.
ANZ J Surg. 2017; 87(1-2):65-69 [PubMed] Related Publications

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting.
METHODS: We performed a prospective cohort study consisting of 30 consecutive patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III).
RESULTS: A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template.
CONCLUSION: SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions.

Nakata B, Tendo M, Okuyama M, et al.
Additional surgical resection after endoscopic mucosal dissection for early gastric cancer: A medium-sized hospital's experience.
Int J Surg. 2016; 36(Pt A):335-341 [PubMed] Related Publications

PURPOSE: In Japan, the majority of early gastric cancers (EGCs) are now treated with endoscopic submucosal dissection (ESD). Patients with non-curative lesions treated by ESD are advised to undergo additional surgical resection (ASR) based on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and Japanese Gastric Cancer Association (JGCA). However, many studies have demonstrated that residual cancer and lymph node metastasis are only rarely found in ASR specimens. Here we retrospectively analyzed the conditions that could enable the avoidance of unnecessary ASR.
METHODS: The ESD data for 114 absolute indication lesions and 26 lesions of expanded indication lesions were analyzed. The indications and the curability were evaluated according to the JGES/JGCA guidelines.
RESULTS: The rates of non-curative resection and ASR were significantly higher in the expanded indication group compared to the absolute indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was performed for six patients. Three of their ARS specimens contained neither residual cancer nor lymph node metastasis, and the pathological findings of the preceding ESD specimens deviated slightly from the curative criteria defined by the guidelines. The conditions of the lesions that did not meet the curative criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal resection with a horizontal margin positive for the mucosal differentiated-type.
CONCLUSIONS: These data suggest that a close follow-up without ASR might be appropriate for patients in the above-mentioned three categories after non-curative ESD for EGC.

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Stomach Cancer

Gastric Cancer

Singh A, Faulx AL
Endoscopic Evaluation in the Workup of Pancreatic Cancer.
Surg Clin North Am. 2016; 96(6):1257-1270 [PubMed] Related Publications

Early diagnosis and accurate staging of pancreatic cancer is very important to plan optimal management strategy. Endoscopy plays an important role in the diagnosis and management of pancreatic cancer. Endoscopic ultrasound imaging (EUS) is the most sensitive modality for diagnosis, especially for small pancreatic tumors; it also allows tissue acquisition for histological diagnosis. Computed tomography scanning and EUS play complementary roles in staging and are comparable in determining resectability. Endoscopic retrograde cholangiopancreatography allows tissue sampling but is limited to palliative biliary drainage in most cases. In this article, we review the role of endoscopy in the diagnosis and management of pancreatic adenocarcinoma, with special emphasis on the use of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP).

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Ngamruengphong S, Canto MI
Screening for Pancreatic Cancer.
Surg Clin North Am. 2016; 96(6):1223-1233 [PubMed] Related Publications

Pancreatic cancer (PC) is a highly fatal disease that can only be cured by complete surgical resection. However, most patients with PC have unresectable disease at the time of diagnosis, highlighting the need to detect PC and its precursor lesions earlier in asymptomatic patients. Screening is not cost-effective for population-based screening of PC. Individuals with genetic risk factors for PC based on family history or known PC-associated genetic syndromes, however, can be a potential target for PC screening programs. This article provides an overview of the epidemiology and genetic background of familial PC and discusses diagnostic and management approaches.

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Kim SY, Kim MJ, Moon HJ, et al.
Application of the downgrade criteria to supplemental screening ultrasound for women with negative mammography but dense breasts.
Medicine (Baltimore). 2016; 95(44):e5279 [PubMed] Related Publications

We investigated whether the application of the downgrade criteria to supplemental screening ultrasound (US) for women with negative mammography but dense breasts can reduce the rate of Breast Imaging Reporting and Data System (BI-RADS) categories 3 to 4a without a loss of cancer detection.This retrospective study was approved by the Institutional Review Board, and the need to obtain informed consent was waived. A total of 3171 consecutive women (978 women, 1173 women, and 1020 women in the first, second, and third year, respectively) with negative mammography but dense breast who underwent radiologist-performed, hand-held supplemental screening US from March 2010 to February 2013 were included. Downgrade criteria for BI-RADS category 2 were complicated cysts ≤5 mm observed as circumscribed, homogeneous, and hypoechoic lesions and circumscribed oval-shaped solid masses ≤5 mm. Changes in the distribution of BI-RADS category, biopsy rate, and cancer detection yield over 3 years were analyzed. Performances of less-experienced (12 fellows with <2 years of experience) and experienced (3 staffs with >12 years of experience) radiologists were compared. Outcomes of initial examinations (prevalence screening) and noninitial examinations (incidence screening) were compared.Application of the downgrade criteria reduced BI-RADS categories 3 to 4a in both less-experienced (from 39.4% to 16.0%, P < 0.001) and experienced radiologists (from 22.6% to 11.1%, P < 0.001) over 3 years. Biopsy rates also significantly decreased from 6.5% to 2.4% (P < 0.001). Cancer detection yield of supplemental screening US was 2.8 per 1000 examinations (9 of 3171: 2 ductal carcinoma in situ and 7 invasive cancers). There were no differences in cancer detection yield per each year (P = 0.539). There was no interval cancer. In noninitial examinations, BI-RADS categories 3 to 4a rates, biopsy rates, and cancer detection rates were lower compared to initial examinations.Application of the downgrade criteria reduced BI-RADS categories 3 to 4a without a loss of cancer detection. We suggest that our downgrade criteria can be used to reduce the false positive rate in the supplemental screening US. Further large-scale, multicenter, prospective studies are needed to validate the effectiveness of the downgrade criteria.

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Destounis S, Johnston L, Highnam R, et al.
Using Volumetric Breast Density to Quantify the Potential Masking Risk of Mammographic Density.
AJR Am J Roentgenol. 2017; 208(1):222-227 [PubMed] Related Publications

OBJECTIVE: The purposes of this study were to compare BI-RADS density categories with quantitative volumetric breast density (VBD) for the reporting of mammographic sensitivity and to identify which patient factors are most predictive of a diagnosis of interval cancer of the breast versus screen-detected cancer.
MATERIALS AND METHODS: This retrospective study included screen-detected cancers (n = 652) and interval cancers (n = 119) identified between January 2009 and December 2012. Multivariate logistic regression analysis was used to determine which patient factors are predictive of a diagnosis of interval cancer. Sensitivity (screen-detected cancer / [screen-detected cancer + interval cancer]) was determined with the BI-RADS 4th edition density categories and an automated equivalent density grade obtained with a proprietary tool. Sensitivity changes within automated density grade categories were investigated by use of quantitative thresholds at the midpoints of each category.
RESULTS: In univariate analysis, age, menopausal status, and breast density were associated with a diagnosis of interval cancer. Of these risk factors, breast density was the only independent factor whether it was assessed by visual BI-RADS category (odds ratio, 3.54; 95% CI, 1.55-8.10), automated density grade (odds ratio, 4.68; 95% CI, 2.26-9.67), or VBD (odds ratio, 4.51; 95% CI, 1.92-10.61). Sensitivity decreased consistently across increasing automated density grade categories from fatty to extremely dense (95%, 89%, 83%, 65%) and less so for visual BI-RADS (82%, 90%, 84%, 66%). Further dichotomization with VBD cutoffs showed a striking linear relation between VBD and sensitivity (R(2) = 0.959).
CONCLUSION: In this study, breast density was the only risk factor significantly associated with a diagnosis of interval cancer versus screen-detected cancer. Quantitative VBD captures the potential masking risk of breast density more precisely than does the widely used visual BI-RADS density classification system.

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USA

Lynes K, Kazmi SA, Robery JD, et al.
Public appreciation of lifestyle risk factors for colorectal cancer and awareness of bowel cancer screening: A cross-sectional study.
Int J Surg. 2016; 36(Pt A):312-318 [PubMed] Related Publications

INTRODUCTION: Prevention of colorectal cancer (CRC) via reduction of lifestyle risk factors, and participation in bowel screening are two ways in which public engagement could lower mortality from colorectal cancer. This study examined public awareness of lifestyle risk factors and bowel screening, with determination of the factors affecting this.
METHODS: A representative population sample (n = 1969) was surveyed using a study specific postal questionnaire to determine demographics, experience of bowel problems, awareness of lifestyle risk factors, knowledge about the incidence of CRC and potential benefits of screening, as well as personal experience of screening.
RESULTS: The majority of respondents were aged over 50 (74%). 77% had either personal experience or a relative/friend with experience of a bowel problem. Knowledge of dietary advice was better than risks relating to weight and physical activity. Awareness of lifestyle risk factors was significantly worse in those less than 50 years old (p = 0.0004) and with a lower level of education (p = 0.0021). Awareness of bowel cancer diagnosis was significantly lower in those less than 50 years old (p=<0.0001). The most frequent reason for non-completion of a screening kit was that the process was dirty and unpleasant.
CONCLUSION: Initiatives are required to improve awareness of younger people with regard to lifestyle risk factors for CRC, especially since this group stand to benefit most from risk reduction. Those with a lower educational level also had poor awareness but felt that the NHS should not prescribe exercise and lifestyle change; targeting this group would need to take this into account.

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Chhor CM, Mercado CL
Abbreviated MRI Protocols: Wave of the Future for Breast Cancer Screening.
AJR Am J Roentgenol. 2017; 208(2):284-289 [PubMed] Related Publications

OBJECTIVE: The purpose of this article is to describe the use of abbreviated breast MRI protocols for improving access to screening for women at intermediate risk.
CONCLUSION: Breast MRI is not a cost-effective modality for screening women at intermediate risk, including those with dense breast tissue as the only risk. Abbreviated breast MRI protocols have been proposed as a way of achieving efficiency and rapid throughput. Use of these abbreviated protocols may increase availability and provide women with greater access to breast MRI.

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Endometrial (Uterus) Cancer

Du J, Li Y, Lv S, et al.
Endometrial sampling devices for early diagnosis of endometrial lesions.
J Cancer Res Clin Oncol. 2016; 142(12):2515-2522 [PubMed] Free Access to Full Article Related Publications

PURPOSE: Endometrial carcinoma is the most common gynecologic malignancy in both developed and some developing countries. Unlike cervical cancer, for which there is routine screening, only patients symptomatic for endometrial carcinoma typically seek medical help for its diagnosis and treatment. Dilatation and curettage (D&C) has been the standard procedure for evaluating suspicious endometrial lesions. The discomfort and injury caused by the D&C procedure, however, restrict its use as a screening method for early diagnosis of endometrial lesions. High-risk endometrial cancer patients would benefit from an effective and low-cost screening test. In recent years, several endometrial devices have been developed and proposed as screening tools.
METHODS: We have reviewed and evaluated the literature relating to the endometrial sampling devices in clinical use or clinical trials, with the goal of comparing devices and identifying the most appropriate ones for screening for endometrial lesions. Eligible literature was identified from systematic PubMed searches, and the relevant data were extracted. Comments, letters, unpublished data, conference proceedings, and case reports were excluded from our search. Seventy-four articles on endometrial sampling devices were obtained for this review.
RESULTS: The main screening devices for endometrial carcinoma are aspiration devices (such as the Vabra aspirator), Pipelle, Tao Brush, and SAP-1 device. Among these devices, the Tao Brush is the most promising endometrial sampler for screening for endometrial lesions. However, its sampling insufficiency, cost, and unsuccessful insertion rate (20 % in nulliparous and 8 % in parous women) are problematic.
CONCLUSIONS: A more accurate and low-cost endometrial sampler, with improved specimen sufficiency and higher sensitivity for endometrial lesions, needs tobe developed and clinically verified.

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Endometrial Cancer

Falcetta FS, Lawrie TA, Medeiros LR, et al.
Laparoscopy versus laparotomy for FIGO stage I ovarian cancer.
Cochrane Database Syst Rev. 2016; 10:CD005344 [PubMed] Related Publications

BACKGROUND: This is an updated version of the original review that was first published in the Cochrane Database of Systematic Reviews 2008, Issue 4. Laparoscopy has become an increasingly common approach to surgical staging of apparent early-stage ovarian tumours. This review was undertaken to assess the available evidence on the benefits and risks of laparoscopy compared with laparotomy for the management of International Federation of Gynaecology and Obstetrics (FIGO) stage I ovarian cancer.
OBJECTIVES: To evaluate the benefits and harms of laparoscopy in the surgical treatment of FIGO stage I ovarian cancer (stages Ia, Ib and Ic) when compared with laparotomy.
SEARCH METHODS: For the original review, we searched the Cochrane Gynaecological Cancer Group Trials (CGCRG) Register, Cochrane Central Register of Controlled Trials (CENTRAL 2007, Issue 2), MEDLINE, Embase, LILACS, Biological Abstracts and CancerLit from 1 January 1990 to 30 November 2007. We also handsearched relevant journals, reference lists of identified studies and conference abstracts. For the first updated review, the search was extended to the CGCRG Specialised Register, CENTRAL, MEDLINE, Embase and LILACS to 6 December 2011. For this update we searched CENTRAL, MEDLINE, and Embase from November 2011 to September 2016.
SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and prospective cohort studies comparing laparoscopic staging with open surgery (laparotomy) in women with stage I ovarian cancer according to FIGO.
DATA COLLECTION AND ANALYSIS: There were no studies to include, therefore we tabulated data from non-randomised studies (NRS) for discussion as well as important data from other meta-analyses.
MAIN RESULTS: We performed no meta-analyses.
AUTHORS' CONCLUSIONS: This review has found no good-quality evidence to help quantify the risks and benefits of laparoscopy for the management of early-stage ovarian cancer as routine clinical practice.

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Ovarian Cancer

Ghahramanian A, Rahmani A, Aghazadeh AM, Mehr LE
Relationships of Fear of Breast Cancer and Fatalism with Screening Behavior in Women Referred to Health Centers of Tabriz in Iran.
Asian Pac J Cancer Prev. 2016; 17(9):4427-4432 [PubMed] Related Publications

BACKGROUND: Fear and fatalism have been proposed as factors affecting breast cancer screening, but the evidence is not strong. This study aimed to determine relationships of fear and fatalism with breast cancer screening behavior among Tabriz women in Iran.
MATERIALS AND METHODS: In a cross- sectional study, 370 women referred to 12 health centers in Tabriz were selected with two-stage cluster sampling and data regarding breast cancer screening, fatalism and fear of breast cancer were collected respectively with a checklist for screening performance, Champions Fear and Pow Fatalism Questionnaires. Data were analyzed by logistic regression with SPSS software version 16.
RESULTS: Only 43% and 23% of participants had undergone breast self- examination and clinical breast examination. Among women older than 40 years, 38.2% had mammography history and only 2.7% of them had done it annually. Although fatalism and fear had a stimulating effects on breast cancer screening performance th relationships were not signi cant (P>0.05). There was a negative significant correlation between fear and fatalism (r= -0.24, p=0.000). On logistic regression analysis, age (OR=1.037, p<0.01) and income status (OR= 0.411, p<0.05) significantly explained BSE and age (OR=1.051, p<0.01) and body mass index (OR= 0.879, p<0.01) explained CBE. Also BMI (OR= 0.074, p<0.05) and income status (OR=0.155, p<0.01) was significantly effective for mammography following.
CONCLUSIONS: Breast cancer screening behavior is inappropriate and affected by family livelihood status and lifestyle leads to weight gain, so that for promoting of screening behavior, economic support to families, lifestyle modification and public education are suggested.

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Breast Cancer Screening

Miyoshi E, Kamada Y
Application of glycoscience to the early detection of pancreatic cancer.
Cancer Sci. 2016; 107(10):1357-1362 [PubMed] Free Access to Full Article Related Publications

The prognosis of pancreatic cancer is extremely poor compared to other cancers. One of the reasons for this is the difficulty of early diagnosis. Surveillance using cancer biomarkers and image diagnosis can enable early detection and has improved the prognosis of hepatocellular carcinoma in Japan. However, it is very difficult to detect pancreatic cancer at an early stage using cancer biomarkers and image diagnosis alone. Fucosylation is one of the most important types of glycosylation involved in cancer and inflammation. We have developed a novel glycocancer biomarker, fucosylated haptoglobin (Fuc-Hpt), and have investigated its usefulness for the diagnosis of pancreatic cancer over approximately 10 years. Recently, we also found that most pancreatic tissues surrounding pancreatic cancer exhibit chronic pancreatitis with fibrosis and/or fatty degeneration. Certain forms of chronic pancreatitis might indicate high risk for the development of pancreatic cancer. In this review, we provide a historical summary of our research on Fuc-Hpt as a cancer biomarker, and discuss a potential early detection system for pancreatic cancer.

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Bergeron C, von Knebel Doeberitz M
The Role of Cytology in the 21st Century: The Integration of Cells and Molecules.
Acta Cytol. 2016; 60(6):540-542 [PubMed] Related Publications

OBJECTIVES: Cervical cancer screening test performance has been hampered by either a lack of sensitivity in Pap cytology or a lack of specificity of human papillomavirus (HPV) testing. This is disturbing for patients and a cause of high costs for health care providers.
STUDY DESIGN: The identification of p16INK4a as a specific marker for the neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in cytopathology specimens.
RESULTS: When compared to molecular HPV tests for triaging minor cytologic atypia, such as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the immunochemical detection of dual p16INK4a/Ki-67-stained cells demonstrates a significantly improved specificity with good relative sensitivity.
CONCLUSIONS: HPV testing has shown earlier detection of persistent high-grade squamous intraepithelial lesions (HSIL) compared to cytology and is more effective in preventing invasive cervical cancer. The next challenge for the HPV primary screening program is to find the best method(s) for selecting, among HPV-positive women, those patients in need of immediate colposcopy because they are at a higher risk of developing a precancerous lesion. An HSIL cytology result and/or dual p16/Ki-67 staining could be the best candidates, but further randomized studies are required before these approaches can be used in routine practice.

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Cervical Cancer

Hooley RJ, Durand MA, Philpotts LE
Advances in Digital Breast Tomosynthesis.
AJR Am J Roentgenol. 2017; 208(2):256-266 [PubMed] Related Publications

OBJECTIVE: Digital breast tomosynthesis (DBT) has rapidly emerged as an important new imaging tool that reduces the masking effect of overlapping fibroglandular tissue, thereby improving breast cancer detection. This article will review key features of DBT including technique, clinical implementation, and benign and malignant imaging findings. We will also present the benefits of DBT in screening, diagnostic workup, and image-guided biopsy.
CONCLUSION: Tomosynthesis improves interpretive performance and will likely replace conventional 2D mammography in clinical practice.

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Lam YH, Bright T, Leong M, et al.
Oesophagectomy is a safe option for early adenocarcinoma arising from Barrett's oesophagus.
ANZ J Surg. 2016; 86(11):905-909 [PubMed] Related Publications

BACKGROUND: Over the last decade, there has been a shift towards endoscopic treatment of high-grade dysplasia (HGD) and T1 stage adenocarcinoma arising in Barrett's oesophagus. Although short-term outcomes are promising, longer-term outcomes remain uncertain and the role of these therapies versus surgery is debated, with surgical mortality rates assumed. However, few studies have specifically determined the outcome for oesophagectomy in the subgroup with HGD or T1 adenocarcinoma. To determine this, we evaluated experience with oesophagectomy for HGD and T1 adenocarcinoma in Barrett's oesophagus.
METHODS: Data were analysed from a prospective audit database for oesophagectomy performed at two public and four associated private hospitals in Adelaide, South Australia. Patients with HGD, T1a and T1b adenocarcinoma who underwent oesophagectomy from 20 February 1998 to 17 February 2012 were identified, and their perioperative, post-operative and survival outcomes were determined.
RESULTS: From 452 oesophagectomy procedures, 63 (13.9%) individuals who underwent surgery for HGD or T1 adenocarcinoma were identified; HGD - 19 (30.1%), T1a - 18 (28.5 %), T1b - 26 (41.3%). Major complications occurred in eight (12.7%) patients including one (1.6%) death following surgery. Five-year survival for HGD and T1a cancers using Kaplan-Meier analysis was not significantly different from a matched general population without cancer.
CONCLUSION: Oesophagectomy for HGD and T1 stage adenocarcinoma in Barrett's oesophagus is associated with favourable outcomes. Outcomes following endoscopic treatments should be benchmarked against these outcomes, not those following oesophagectomy for advanced cancer.

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Cancer of the Esophagus

Esophageal Cancer

Théberge I, Vandal N, Langlois A, et al.
Detection Rate, Recall Rate, and Positive Predictive Value of Digital Compared to Screen-Film Mammography in the Quebec Population-Based Breast Cancer Screening Program.
Can Assoc Radiol J. 2016; 67(4):330-338 [PubMed] Related Publications

PURPOSE: The study sought to compare performance indicators of computed radiography (CR) using different plate readers, digital direct radiography (DR), and screen-film mammography (SFM) in a population-based screening program.
METHODS: This analysis involved women 50-69 years of age who participated in the breast screening program of Quebec (Canada) and who had screening mammogram between January 1, 2007, and September 30, 2012. The detection rate, recall rate, and positive predictive value of CR (n = 672,125 mammograms) and DR (n = 60,023) were compared to SFM (n = 782,894) using mixed-effect logistic regression, adjusting for potential confounders. No institutional review board approval was required.
RESULTS: CR was not associated with change in cancer detection rate (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.88-1.03), but with a small increase in recall rate (OR: 1.03; 95% CI: 1.01-1.06) compared to SFM. The association of CR with recall rate varies with the CR plate reader manufacturer (P < .0001). DR was not associated with change in detection rate (OR: 1.06; 95% CI: 0.89-1.25), but with an increase in the recall rate (OR: 1.25; 95% CI: 1.19-1.30) compared to SFM.
CONCLUSIONS: In our screening program, digital mammograms gave detection rates equivalent to those of SFM, but with an increase of recall rate, particularly for DR. If this situation persists, the adoption of DR may increase the adverse effects of screening with little or no benefit for women.

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Larouche G, Chiquette J, Plante M, et al.
Usefulness of Canadian Public Health Insurance Administrative Databases to Assess Breast and Ovarian Cancer Screening Imaging Technologies for BRCA1/2 Mutation Carriers.
Can Assoc Radiol J. 2016; 67(4):308-312 [PubMed] Related Publications

PURPOSE: In Canada, recommendations for clinical management of hereditary breast and ovarian cancer among individuals carrying a deleterious BRCA1 or BRCA2 mutation have been available since 2007. Eight years later, very little is known about the uptake of screening and risk-reduction measures in this population. Because Canada's public health care system falls under provincial jurisdictions, using provincial health care administrative databases appears a valuable option to assess management of BRCA1/2 mutation carriers. The objective was to explore the usefulness of public health insurance administrative databases in British Columbia, Ontario, and Quebec to assess management after BRCA1/2 genetic testing.
METHODS: Official public health insurance documents were considered potentially useful if they had specific procedure codes, and pertained to procedures performed in the public and private health care systems.
RESULTS: All 3 administrative databases have specific procedures codes for mammography and breast ultrasounds. Only Quebec and Ontario have a specific procedure code for breast magnetic resonance imaging. It is impossible to assess, on an individual basis, the frequency of others screening exams, with the exception of CA-125 testing in British Columbia. Screenings done in private practice are excluded from the administrative databases unless covered by special agreements for reimbursement, such as all breast imaging exams in Ontario and mammograms in British Columbia and Quebec. There are no specific procedure codes for risk-reduction surgeries for breast and ovarian cancer.
CONCLUSION: Population-based assessment of breast and ovarian cancer risk management strategies other than mammographic screening, using only administrative data, is currently challenging in the 3 Canadian provinces studied.

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Pelletier E, Daigle JM, Defay F, et al.
Frequency and Determinants of a Short-Interval Follow-up Recommendation After an Abnormal Screening Mammogram.
Can Assoc Radiol J. 2016; 67(4):322-329 [PubMed] Related Publications

PURPOSE: After imaging assessment of an abnormal screening mammogram, a follow-up examination 6 months later is recommended to some women. Our aim was to identify which characteristics of lesions, women, and physicians are associated to such short-interval follow-up recommendation in the Quebec Breast Cancer Screening Program.
METHODS: Between 1998 and 2008, 1,839,396 screening mammograms were performed and a total of 114,781 abnormal screens were assessed by imaging only. Multivariate analysis was done with multilevel Poisson regression models with robust variance and generalized linear mixed models.
RESULTS: A short-interval follow-up was recommended in 26.7% of assessments with imaging only, representing 2.3% of all screens. Case-mix adjusted proportion of short-interval follow-up recommendations varied substantially across physicians (range: 4%-64%). Radiologists with high recall rates (≥15%) had a high proportion of short-interval follow-up recommendation (risk ratio: 1.82; 95% confidence interval: 1.35-2.45) compared to radiologists with low recall rates (<5%). The adjusted proportion of short-interval follow-up was high (22.8%) even when a previous mammogram was usually available.
CONCLUSIONS: Short-interval follow-up recommendation at assessment is frequent in this Canadian screening program, even when a previous mammogram is available. Characteristics related to radiologists appear to be key determinants of short-interval follow-up recommendation, rather than characteristics of lesions or patient mix. Given that it can cause anxiety to women and adds pressure on the health system, it appears important to record and report short-interval follow-up and to identify ways to reduce its frequency. Short-interval follow-up recommendations should be considered when assessing the burden of mammography screening.

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Hruska CB
Molecular Breast Imaging for Screening in Dense Breasts: State of the Art and Future Directions.
AJR Am J Roentgenol. 2017; 208(2):275-283 [PubMed] Related Publications

OBJECTIVE: The purposes of this review are to discuss the motivation for supplemental screening, to address molecular breast imaging (MBI) radiation dose concerns, and to provide an updated guide to current MBI technology, clinical protocols, and screening performance. Future directions of MBI are also discussed.
CONCLUSION: MBI offers detection of mammographically occult cancers in women with dense breasts. Although MBI has been under investigation for nearly 15 years, it has yet to gain widespread adoption in breast screening.

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Veijalainen O, Kares S, Kujala P, et al.
Human papillomavirus test with cytology triage in organized screening for cervical cancer.
Acta Obstet Gynecol Scand. 2016; 95(11):1220-1227 [PubMed] Related Publications

INTRODUCTION: In randomized studies, testing for high-risk (HR) human papillomavirus (hrHPV) has been more sensitive than conventional cytology in detecting cervical intraepithelial neoplasia (CIN). The aim of this study was to evaluate the performance of HPV testing in the setting of an organized routine screening program.
MATERIAL AND METHODS: Since 2012, 35- to 60-year-old women living in the city of Tampere have been screened with the Abbott RealTime hrHPV test. HPV-negative women are referred to the next screening round in five years. HPV-positive women are triaged with conventional cytology, and women with at least low-grade squamous intraepithelial lesion (LSIL(+) ) are referred to colposcopy. The remaining HPV-positive women are referred for re-testing after 12 months, and then all HPV-positive women are referred to colposcopy. The data from the last cohort with cytological screening (screened in 2011) is presented for comparison.
RESULTS: A total 5637 (70%) women attended the first round of HPV screening, and 369 were HPV-positive. Of them, 54 women LSIL(+) were referred to colposcopy, resulting in 16 CIN2(+) lesions found. Of the remaining HPV-positive women, 66% were still positive one year later, and were referred to colposcopy, with 18 additional CIN2(+) lesions found. The attendance rate to the last round of cytological screening was 71% (5814 women). Sixty-four women with LSIL(+) cytology were referred to colposcopy, and 11 CIN2(+) lesions were found. Of the 777 women with borderline cytology and scheduled for reflex screening in the following year, 109 (19%) had ASC-US(+) , and 57 underwent colposcopy, resulting in six additional CIN2(+) lesions found. The total detection rate of CIN2(+) was significantly higher in the HPV-screened cohort (6.0/1000 vs. 2.9/1000, p = 0.015). However, the total colposcopy rate was 4% vs. 2%, respectively (p < 0.001).
CONCLUSION: Human papillomavirus testing also seems to be more sensitive than cytology in detecting CIN2(+) lesions in the setting of a routine organized screening program, besides in the context of randomized trials. The problem of an increased colposcopy rate needs to be addressed in the future.

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Cervical Cancer

Li D, Chen L, Wang H, et al.
Clinical application of a rapid cervical cancer screening method: Folate receptor-mediated staining of cervical neoplastic epithelia.
Asia Pac J Clin Oncol. 2017; 13(1):44-52 [PubMed] Related Publications

AIM: A newly developed cervical cancer screening method - folate receptor-mediated epithelium staining utilizes methylene blue internalized by folate receptor-mediated endocytosis to stain cervical intra-epithelial neoplasia. We test the clinical feasibility of this method in this study.
METHODS: A total of 14 344 women who were at least 21 years old and had been sexually active, participated in the study. In gynecological clinics, participants underwent cervical cancer screening with folate receptor-mediated epithelium staining followed by cytology sampling. The color change of methylene blue in the cervical neoplastic epithelium can then be detected by the cotton swabs placed inside the cervix. A change of color to blue, bluish black or black is positive, whereas a change of color to green or no color change indicates negative result. Three hundred and twenty-three women who were positive with either or both tests had histopathologic diagnosis.
RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of folate receptor-mediated epithelium staining for cervical intra-epithelial neoplasia grade 2 and worse was 85.7%, 76.4%, 61.3% and 92.5%, respectively. Folate receptor-mediated epithelium staining had moderate agreement with cytology thresholded at atypical squamous cells, unable to exclude a high grade intra-epithelial lesion and was more sensitive that the later (85.7% vs 74.5% for intra-epithelial neoplasia grade 2 and worse; 89.2% vs 75.4% for intra-epithelial neoplasia grade 3 and worse).
CONCLUSION: Folate receptor-mediated epithelium staining is capable of detecting cervical precancerous and cancerous lesions rapidly and cost-effectively.

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Cervical Cancer

Welch HG, Prorok PC, O'Malley AJ, Kramer BS
Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness.
N Engl J Med. 2016; 375(15):1438-1447 [PubMed] Related Publications

Background The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). Results After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality. Conclusions Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.

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