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1.
Tamotsu Sugai Makoto Eizuka Noriyuki Arakawa Mitsumasa Osakabe Wataru Habano Yasuko Fujita Eiichiro Yamamoto Hiroo Yamano Masaki Endoh Takayuki Matsumoto Hiromu Suzuki 《Gastric cancer》2018,21(5):765-775
Background
We attempted to identify the molecular profiles of gastric intramucosal neoplasia (IMN; low-grade dysplasia, LGD; high-grade dysplasia, HGD; intramucosal cancer, IMC) by assessing somatic copy number alterations (SCNAs) stratified by microsatellite status (microsatellite stable, MSS; microsatellite instable, MSI). Thus, microsatellite status was determined in 84 tumors with MSS status and 16 tumors with MSI status.Methods
One hundred differentiated type IMNs were examined using SCNAs. In addition, genetic mutations (KRAS, BRAF, PIK3CA, and TP53) and DNA methylation status (low, intermediate and high) were also analyzed. Finally, we attempted to identify molecular profiles using a hierarchical clustering analysis.Results
Three patterns could be categorized according to SCNAs in IMNs with the MSS phenotype: subgroups 1 and 2 showing a high frequency of SCNAs, and subgroup 3 displaying a low frequency of SCNAs (subgroup 1 > 2 > 3 for SCNA). Subgroup 1 could be distinguished from subgroup 2 by the numbers of total SCNAs (gains and losses) and SCN gains (subgroup 1 > 2). The SCNA pattern of LGD was different from that of HGD and IMC. Moreover, IMNs with the MSI phenotype could be categorized into two subtypes: high frequency of SCNAs and low frequency of SCNAs. Genetic mutations and DNA methylation status did not differ among subgroups in IMNs.Conclusion
Molecular profiles stratified by SCNAs based on microsatellite status may be useful for elucidation of the mechanisms of early gastric carcinogenesis.2.
Dae Gon Ryu Cheol Woong Choi Dae Hwan Kang Hyung Wook Kim Su Bum Park Su Jin Kim Hyeong Seok Nam 《Gastric cancer》2017,20(4):671-678
Background and study aims
Although the Vienna Classification recommends endoscopic resection for gastric high-grade dysplasia (HGD), many resected lesions are diagnosed as gastric cancer after endoscopic resection. This study aims to evaluate the clinical outcomes of gastric HGD identified by endoscopic forceps biopsy (EFB) after endoscopic submucosal dissection (ESD) and factors associated with discrepant results.Patients and methods
From December 2008 to July 2015, a total of 427 lesions diagnosed as initial HGD by EFB were enrolled. The rate of early gastric cancer (EGC) and factors predicting diagnosis upgrade were analyzed retrospectively.Results
Tumors ranged between 2 and 65 mm in size (median 12.59). En bloc and complete resection rates were 97.4 and 95.3%, respectively. The diagnostic discrepancy rate was 76.3%. Upgrade and downgrade rates of pathological diagnoses were 66.5 and 9.8%, respectively. Central depression (OR 4.151), nodular surface (OR 5.582), surface redness (OR 2.926), lesion location (upper third of the stomach) (OR 3.894), and tumor size ≥10 mm (OR 2.287) were significantly associated with EGC. Nodular surface (OR 2.746), submucosal fibrosis (OR 3.958), lesion location (upper third of the stomach) (OR 6.652), and tumor size ≥10 mm (OR 4.935) significantly predicted invasive submucosal cancer.Conclusions
Central depression, nodular surface, surface redness, lesion location, large tumor size, and submucosal fibrosis were associated with EGC or submucosal cancer. Caution must be used in treating lesions with these features with ESD.3.
Francesca Pigatto Adrian Bateman David Bunyan Paul Strike Esta Wilkins Claire Curtis Philippa Duncan Denzil May Karen Nugent Diana Eccles 《Hereditary cancer in clinical practice》2004,2(4):175-184
Aim
To determine a cost-efficient strategy for HNPCC molecular diagnostic testing.Methods
138 families referred to a Regional Genetics Service had hMLH1 and hMSH2 mutation analysis. The sensitivity and specificity of clinical selection criteria with or without immunohistochemistry (IHC) and microsatellite instability (MSI) analysis to further refine case selection and the effect of these approaches on the cost of mutation analysis were examined.Results
Clearly deleterious mutations were identified in 49/138 (35.5%) of all families tested. The most sensitive criteria for identifying families with MMR mutations were the full Bethesda guidelines but these have poor specificity. IHC and MSI were useful pre-screening tools.Conclusion
A cost-efficient approach in laboratories where IHC and/or MSI analysis are available, is to use inclusive (non-specific) criteria to select cases, followed by IHC and then MSI. Where one or both results are abnormal, proceed to further mutation analysis. Where MSI or IHC or tumour blocks are not available, more restrictive clinical criteria may be more appropriate for cost-efficient case selection.4.
Background
Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models.Methods
MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed.Results
A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group.Conclusions
Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies.5.
Bin Huang Elizabeth Pollock Li Zhu Jessica P. Athens Ron Gangnon Eric J. Feuer Thomas C. Tucker 《Cancer causes & control : CCC》2018,29(2):279-287
Purpose
To develop a composite Cancer Burden Index and produce 95% confidence intervals (CIs) as measures of uncertainties for the index.Methods
The Kentucky Cancer Registry has developed a cancer burden Rank Sum Index (RSI) to guide statewide comprehensive cancer control activities. However, lack of interval estimates for RSI limits its applications. RSI also weights individual measures with little inherent variability equally as ones with large variability. To address these issues, a Modified Sum Index (MSI) was developed to take into account of magnitudes of observed values. A simulation approach was used to generate individual and simultaneous 95% CIs for the rank MSI. An uncertainty measure was also calculated.Results
At the Area Development Districts (ADDs) level, the ranks of the RSI and the MSI were almost identical, while larger variation was found at the county level. The widths of the CIs at the ADD level were considerably shorter than those at the county level.Conclusion
The measures developed for estimating composite cancer burden indices and the simulated CIs provide valuable information to guide cancer prevention and control effort. Caution should be taken when interpreting ranks from small population geographic units where the CIs for the ranks overlap considerably.6.
Background
Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may play different roles in the development of colon cancer and rectal cancer, and we have specifically investigated their contribution to the development of rectal cancer at young age.Methods
Thirty rectal cancers diagnosed before the age of 50 were characterized for DNA-ploidy, MSI, mutations of KRAS and CTNNB1 and immunohistochemical expression of p53, β-catenin and of the mismatch repair (MMR) proteins MLH1 and MSH2.Results
DNA aneuploidy was detected in 21/30 tumors, KRAS mutations in 6 tumors, no mutations of CTNNB1 were detected but immunohistochemical staining for β-catenin showed nuclear staining in 6 tumors, and immunohistochemical expression of p53 was detected in 18 tumors. MSI was detected in 3/30 tumors, all of which showed and immunohistochemical loss of staining for the MMR protein MSH2, which strongly indicates a phenotype associated with hereditary nonpolyposis colorectal cancer (HNPCC).Conclusions
MSI occurs only in a small fraction of the tumors from young patients with rectal cancer, but when present it strongly indicates an underlying HNPCC-causing mutation, and other mechanisms than HNPCC thus cause rectal cancer in the majority of young patients.7.
Aim
To explore information-seeking behaviors on links between cancers and environment.Method
Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.Results
The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.Conclusion
Little information is sought on links between cancers and environment.8.
Christophe Van Neste Alexander Laird Fiach O’Mahony Wim Van Criekinge Dieter Deforce Filip Van Nieuwerburgh Thomas Powles David J. Harrison Grant D. Stewart Tim De Meyer 《Cellular oncology (Dordrecht)》2017,40(3):293-297
Purpose
Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer.Methods
DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort.Results
We found that six genes were differentially methylated in the test samples, of which four were linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-1299, ANKRD2). Three of these genes were also found to be significantly differentially methylated in the validation cohort, indicating that the observed effects are genuine.Conclusion
Tissue ischaemia during normal surgical removal of tumour can cause epigenetic changes. Based on these results, we conclude that the impact of sampling procedures in clinical epigenetic studies should be considered and discussed, particularly after inducing hypoxia/ischaemia, which occurs in most oncological surgery procedures through which tissues are collected for translational research.9.
Rin Yamada Tatsuro Yamaguchi Takeru Iijima Rika Wakaume Misato Takao Koichi Koizumi Tsunekazu Hishima Shin-ichiro Horiguchi 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(3):504-513
Background
The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.Methods
Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.Results
The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).Conclusions
Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.10.
Liisa Chang Minna Chang Hanna M. Chang Fuju Chang 《Journal of gastrointestinal cancer》2017,48(4):305-313
Background
Colorectal carcinomas with high-frequency microsatellite instability (MSI-H) account for 15% of all colorectal cancers, including 12% of sporadic cases and 3% of cancers associated with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome, HNPCC). Lynch syndrome is an autosomal dominant hereditary cancer syndrome, caused by germline mutations in mismatch repair genes, including MLH1, MSH2, MSH6 and PMS2.Methods
Published articles from peer-reviewed journals were obtained from PubMed, Google Scholar and Clinicaltrials.gov. Based on the recent research data, we provide an update on the MSI testing, along with the evolving role of MSI in diagnosis, prognosis and treatment of colorectal cancers.Results
Studies have led to significant advances in the molecular pathogenesis and clinicopathological characteristics of MSI-H colorectal cancers. Emerging evidence suggests that colorectal cancers with MSI-H show different outcome and treatment response from those with microsatellite stable (MSS) tumors. Therefore, MSI testing is essential not only in the genetic context, but it may also have important prognostic and predictive value of response to chemotherapy and immunotherapy.Conclusions
Many experts and professional authorities have recommended a universal MSI testing in all individuals newly diagnosed with colorectal cancers.11.
Ji Hyeon Joo Su Ssan Kim Seung-Do Ahn Eun Kyung Choi Jin Hong Jung Yuri Jeong Sei Hyun Ahn Byung Ho Son Jong Won Lee Hee Jung Kim Beom Seok Go Hak Hee Kim Joo Hee Cha Hee Jung Shin Eun Young Chae 《Breast cancer research and treatment》2017,166(2):511-518
Purpose
To analyze the prognostic role of pathologic confirmation of internal mammary lymph nodes (IMNs) for breast cancer patients who received neoadjuvant chemotherapy.Methods
Of the patients who were treated with neoadjuvant chemotherapy, surgery, and radiation therapy between 2009 and 2013, 114 women had suspicious IMNs and FNAB was attempted. Clinical IMN metastasis was diagnosed by 18F-FDG PET/CT positivity or pathologic confirmation (N = 70). Patients were divided into the FNAB(+) or FNAB(?) IMN group.Results
The pathologic confirmation rate was 57% (40 of 70 patients). Rates were 74% in US-positive, 70% in MRI-positive, and 55% in PET-positive patients. Nodal stage was cN2b (6%) or cN3b (94%). Five-year progression-free survival (PFS) was significantly worse in patients with FNAB(+) IMN metastasis than FNAB(?) IMN metastasis (61% vs. 87%, P = 0.03). FNAB(+) IMN patients showed worse distant metastasis and regional recurrence-free survival without statistical significance (69% vs. 86%, P = 0.06, and 81% vs. 96%, P = 0.06). With median follow-up of 50.5 months (13.0–97.0 months), overall survival at 5 years was 77%, and PFS was 72%.Conclusions
Patients with FNAB-proven IMN metastasis had worse treatment outcomes compared to patients with clinically diagnosed IMN metastasis in cN2b/N3b breast cancer.12.
Background
Non-small cell lung cancer (NSCLC) accounts for ca. 75% of malignant epithelial neoplasms of the lungs. In recent years profound insight has been gained regarding the molecular mechanisms of lung carcinogenesis and subsequently new targeted therapies as well as immunotherapies have been developed. These advances have had a significant impact on routine diagnostics in pathology.Objective
The article aims to give an overview of the most common histological subtypes of NSCLC as well as the morphological, immunohistochemical and molecular characteristics.Material and methods
Selective search of the PubMed database.Results and discussion
Adenocarcinomas, squamous cell carcinomas and large cell carcinomas are the most common histological subtypes. With the ancillary methods available in routine pathology even poorly differentiated tumors can be assigned to these entities. The NSCLC show numerous genetic changes of which alterations of EGFR, MET, ALK1 and ROS1 are target structures for personalized therapy.13.
Aims
This study aims to identify the most used defense mechanisms in oncology clinicians.Method
Defenses were evaluated conducting an interview with a simulated patient in 62 nurses and 51 physicians by means of the Defense Mechanism Rating Scales for Clinician (DMRS-C).Results
Displacement (20%), rationalization (19.1%) and intellectualization (12.1%) were the most frequently observed mechanisms.Conclusion
These results underline the need to include the topic of the stress induced by the interview in clinicians during communication skills training in oncology.14.
Purpose
This article aims to discuss the optimal surgical treatment for Phyllodes Tumor. A general overview of each grade will be presented along with relevant findings in recent literature. An argument for a modification to current practice standards and guidelines will be introduced as histological grading has become increasingly important.Recent Findings
Based on our literature review, benign phyllodes tumors have a mean local recurrence rate of 6.9% and a mean distant metastasis rate of 0.01%. Recent studies have revealed there is no statistical difference in local recurrence for patients with positive or negative margins following tumor resection of the benign grade.Summary
The National Comprehensive Cancer Network recommends wide local excisions with negative margins of 1 cm for all Phyllodes Tumors. However, we believe these guidelines are obsolete as the histological benign grade has extremely low rates of local recurrence and metastasis. In order to decrease patient morbidity, close surveillance and observation should be considered over standard practice following a positive margin in benign Phyllodes Tumors.15.
Michael B. Rothberg Bo Hu Laura Lipold Sarah Schramm Xian Wen Jin Andrea Sikon Glen B. Taksler 《Cancer causes & control : CCC》2018,29(3):297-304
Importance
Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.Objective
To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.Design
The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.Setting
The study was conducted in a setting of 33 primary care practices from 2004 to 2010.Participants
The participants of the study were women aged ≥?30 years.Main outcome and measures
CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.Results
The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).Conclusions and relevance
A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.16.
17.
Clotilde Delerce Olivia Bailly Amine Bouhamama Sophie Couchon Frank Pilleul Arnaud Thivolet Charles Mastier 《Clinical sarcoma research》2018,8(1):22
Background
Review of the first documented case of aortic wall metastasis from a limb sarcoma.Case presentation
In a 56-year-old woman with a diagnosis of a high-grade limb fibrosarcoma, an aortic metastasis was revealed by a fast growing aneurysm of the descending thoracic aorta. This was managed with an endoprosthesis.Conclusion
The presence of an aneurysm in a patient with a sarcoma with a high potential for metastasis and poor cardiovascular risk factors should alert physicians.18.
Background
Endocrine tumours of the gastro-intestinal tract are rare and predominate in the small intestine and in the appendix, less commonly in the colon and the rectum.Aim
The aim of this study is to analyze clinical and pathologic features of an endocrine tumour of the colon and the rectum diagnosed in the Department of Pathology (Sousse, Tunisia).Methods
Five cases were diagnosed between 1992 and 2006 in our hospital unit. The medical records of the affected patients were analyzed. The pathological material was reviewed and the tumours were classified according to 2000 WHO classification.Results
The study population consisted of 2 male and 3 female patients. Their median age was 55 years. Two poorly differentiated endocrine carcinomas of the colon, and one colic and two rectal well differentiated endocrine carcinoma were identified.Conclusion
This study illustrates the importance of adequately diagnosing endocrine tumours because their treatment and prognosis are different from those of conventional carcinoma.19.
Wojciech Lubiński Stanisław Zajączek Zbigniew Sych Krzysztof Penkala Olgierd Palacz Jan Lubiński 《Hereditary cancer in clinical practice》2004,2(4):193-196
Purpose
To asses the retinal pigment epithelium (RPE) function measured by EOG testing in patients with neurofibromatosis type 1 (NF-1). Our preliminary EOG results suggested dysfunction of the RPE in individuals with NF-1. In order to confirm our initial results we performed EOG examination on a larger group of NF-1 patients.Patients
Studies were performed on 36 patients with clinically diagnosed NF-1 and compared to normal healthy controls.Methods
Standard EOG recordings were performed in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards.Results
In NF-1 patients the Arden indexes of the EOG test were significantly higher primarily due to the lower values of dark troughs. Supernormal EOGs (exceeding the value of the mean + 2 SD from the control group) were present in 58% of NF-1 patients.Conclusions
Dysfunction of the RPE is a characteristic feature of individuals with NF-1.20.
Shinichiro Yasukawa Satoshi Kano Hiromitsu Hatakeyama Yuji Nakamaru Dai Takagi Takatsugu Mizumachi Masanobu Suzuki Takayoshi Suzuki Akira Nakazono Shinya Tanaka Hiroshi Nishihara Akihiro Homma 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(5):835-843