Faster surgery initiation in oral cancer patients during the COVID-19 pandemic in Osaka, Japan.

BACKGROUND: We investigated the impact of the COVID-19 pandemic on oral cancer (OC), comparing diagnosis and number of pre-operative days in the diagnosis of OC in 2019 (pre-COVID-19) and that in 2020 (during the COVID-19 pandemic). METHODS: Using data from a cancer registry-based study on the impact of COVID-19 on cancer care in Osaka (CanReCO), we collected details of sex, age, residential area, cancer site, date of diagnosis, clinical stage at first treatment and number of pre-operative days in OC patients. RESULTS: A total of 1470 OC cases were registered. Incidence of OC before and during COVID-19 was 814 and 656 cases, respectively. During the first wave of the pandemic (March to May 2020), incidence was about half that in the same period in 2019 (2019; n = 271, 2020; n = 145). Number of pre-operative days (median number of days between the first hospital visit and surgery date) was significantly shorter during the COVID-19 year (24.5 days) than in the pre-COVID-19 year (28 days, p = 0.0015). CONCLUSIONS: Incidence of OC during the COVID-19 pandemic was lower than in pre-COVID-19. Despite disruption in the healthcare system, the number of pre-operative days for OC cases was shorter during the pandemic.

Early Detection of Radiation Pneumonitis on Cone-Beam CT Images During a Course of Radiotherapy: A Case Series Report.

Background and aim Radiation pneumonitis (RP) is a critical pulmonary toxicity following dose delivery to the lung, and it is usually diagnosed after radiotherapy courses are completed. Because RP may result in a lethal complication, a practical method for detecting early-phase RP is awaited. In this article, we describe our experience through a variety of clinical cases and discuss treatment decisions and lessons we have made and learned. Materials and methods A daily cone-beam computed tomography (CBCT) scan was employed with a lung window setting to detect the early-phase RP during treatment courses. For the past five years, thirty patients were diagnosed with RP, and eight patients were detected during radiotherapy courses on the CBCT images. Our best efforts were made in detecting early ground-glass opacity and early RP on CBCT images prior to symptoms. The eight cases were described in more detail with CBCT or CT images. Results and discussion Initially, RP was detected at 50 Gy or greater. However, more careful CBCT observation resulted in earlier detection at around 40 Gy. Then, a new problem arose whether the treatment should be terminated. It was reported that early RP development was associated with higher-grade complications, and therefore it is preferable to terminate radiotherapy once we detect even early-phase RP. However, termination in the middle of the treatment course may significantly reduce the therapeutic effect. In our experience, patients with favorable clinical status may continue to receive radiotherapy with careful observation of lung parenchyma on CBCT images and clinical data, such as Krebs Von den Lungen-6 (KL-6) and C-reactive protein (CRP). Conclusion We have shown that early detection of RP may be feasible during radiotherapy courses by daily monitoring of CBCT lung images. Further studies are awaited to proceed.

Travel patterns of patients seeking cancer care during the COVID-19 pandemic: Multi-centre cohort study in Osaka, Japan.

BACKGROUND: In Japan, provision of equal access to cancer care is intended to be achieved via secondary medical areas (SMAs). However, the percentage of patients receiving care within the residential area varies by SMA in Osaka Prefecture. We aimed to assess the effect size of factors associated with patient mobility, and whether patient mobility was affected by the COVID-19 pandemic. METHODS: Records of patients diagnosed with stomach, colorectal, lung, breast, cervical, oesophageal, liver or pancreatic cancer during 2019-2020 were extracted from multi-centre hospital-based cancer registry data. Odds ratios of whether a patient received care within the SMA of residence were set as the outcome. A multivariable model was built using generalised estimating equations with multiple imputation for missing data. Change in patient mobility after the pandemic was examined by deriving age- and SMA-specific adjusted ORs (aORs). RESULTS: A total of 78,839 records were included. Older age, more advanced stage and palliative care had up to 1.69 times higher aORs of receiving care within their own area. Patients with oesophageal, liver or pancreatic cancer tended to travel outside their area with aORs ranging from 0.71 to 0.90. Patients aged ≤ 79 and living in the East and South SMAs tended to remain in their area with aORs ranging from 1.05 to 1.11 after the pandemic. CONCLUSION: Patient mobility decreased for higher age and stage. It also varied by SMA, cancer site and treatment type. POLICY SUMMARY: Our results need to be linked with resource inputs to help policymakers decide whether to intervene to address current efficiency or equity issues.

Patterns of staging, treatment, and mortality in gastric, colorectal, and lung cancer among older adults with and without preexisting dementia: a Japanese multicentre cohort study.

BACKGROUND: Little is known about dementia's impact on patterns of diagnosis, treatment, and outcomes in cancer patients. This study aimed to elucidate the differences in cancer staging, treatment, and mortality in older cancer patients with and without preexisting dementia. METHODS: Using cancer registry data and administrative data from 30 hospitals in Japan, this multicentre retrospective cohort study examined patients aged 65-99 years who were newly diagnosed with gastric, colorectal, or lung cancer in 2014-2015. Dementia status (none, mild, and moderate-to-severe) at the time of cancer diagnosis was extracted from clinical summaries in administrative data, and set as the exposure of interest. We constructed multivariable logistic regression models to analyse cancer staging and treatment, and multivariable Cox regression models to analyse three-year survival. RESULTS: Among gastric (n = 6016), colorectal (n = 7257), and lung (n = 4502) cancer patients, 5.1%, 5.8%, and 6.4% had dementia, respectively. Patients with dementia were more likely to receive unstaged and advanced-stage cancer diagnoses; less likely to undergo tumour resection for stage I, II, and III gastric cancer and for stage I and II lung cancer; less likely to receive pharmacotherapy for stage III and IV lung cancer; more likely to undergo tumour resection for all-stage colorectal cancer; and more likely to die within three years of cancer diagnosis. The effects of moderate-to-severe dementia were greater than those of mild dementia, with the exception of tumour resection for colorectal cancer. CONCLUSION: Older cancer patients with preexisting dementia are less likely to receive standard cancer treatment and more likely to experience poorer outcomes. Clinicians should be aware of these risks, and would benefit from standardised guidelines to aid their decision-making in diagnosing and treating these patients.

Impact of coexisting diabetes on survival and risk of developing second primary cancer in diabetes patients receiving drug therapy: A multicenter retrospective cohort study of patients with cancer in Japan.

AIMS/INTRODUCTION: We investigated the association between coexisting diabetes at the time of cancer diagnosis, and the overall survival and incidence of second primary cancer in patients with cancer and receiving drug therapy for diabetes. MATERIALS AND METHODS: We used cancer registry and administrative data of patients diagnosed with cancer at designated cancer care hospitals in Osaka Prefecture between 2010 and 2015. The presence of diabetes was identified from the prescription records of antidiabetic drugs in Diagnosis Procedure Combination System data. After adjusting for patient characteristics, we compared overall survival between patients with cancer with coexisting diabetes and those without coexisting diabetes using the Cox proportional hazards model. In addition, the impact of coexisting diabetes on the risk of developing second primary cancer was evaluated using a competing risk analysis. RESULTS: Of the 131,701 patients with cancer included in the analysis, 6,135 (4.7%) had coexisting diabetes. The 5-year survival rates for patients with and without coexisting diabetes were 56.2% (95% confidence interval 54.8-57.6) and 72.7% (95% confidence interval 72.4-73.0), respectively. Coexisting diabetes was associated with a higher risk of developing second primary cancer (subdistribution hazard ratio 1.23; 95% confidence interval 1.08-1.41). In site-specific analysis, coexisting diabetes was associated with an increased risk for the development of second primary cancer of multiple myeloma, and cancer of the uterus, pancreas and liver. CONCLUSIONS: Coexisting diabetes was associated with a higher mortality and risk of developing second primary cancer in Japanese patients with cancer and on drug therapy for diabetes.

Incidence of second primary cancers among survivors of childhood cancer: A population-based study, Osaka, Japan, 1975-2015.

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

Socioeconomic disparities in cancer survival: Relation to stage at diagnosis, treatment, and centralization of patients to accredited hospitals, 2005-2014, Japan.

BACKGROUND: Cancer survival varies by socioeconomic status in Japan. We examined the extent to which survival disparities are explained by factors relevant to cancer control measures (promoting early-stage detection, standardizing treatment, and centralizing patients to government-accredited cancer hospitals [ACHs]). METHODS: From the Osaka Cancer Registry, patients diagnosed with solid malignant tumors during 2005-2014 and aged 15-84 years (N = 376,077) were classified into quartiles using the Area Deprivation Index (ADI). Trends in inequalities were assessed for potentially associated factors: early-stage detection, treatment modality, and utilization of ACH (for first contact/diagnosis/treatment). 3-year all-cause survival was computed by the ADI quartile. Multivariable Cox regression models were used to assess survival disparities and their trends through a series of adjustment for the potentially associated factors. RESULTS: During 2005-2014, the most deprived ADI quartile had lower rates than the least deprived quartile for early-stage detection (42.6% vs. 48.7%); receipt of surgery (58.1% vs. 64.1%); and utilization of ACH (83.5% vs. 88.4%). While rate differences decreased for receipt of surgery and utilization of ACH (Annual Percent Change = -3.2 and - 11.9, respectively) over time, it remained unchanged for early-stage detection. During 2012-2014, the most deprived ADI quartile had lower 3-year survival than the least deprived (59.0% vs. 69.4%) and higher mortality (Hazard Ratio [HR] = 1.32, adjusted for case-mix): this attenuated with additional adjustment for stage at diagnosis (HR = 1.23); treatment modality (HR = 1.20); and utilization of ACH (HR = 1.19) CONCLUSIONS: Despite improvements in equalizing access to quality cancer care during 2005-2014, survival disparities remained. Interventions to reduce inequalities in early-stage detection could ameliorate such gaps.

Diagnosis and treatment of digestive cancers during COVID-19 in Japan: A Cancer Registry-based Study on the Impact of COVID-19 on Cancer Care in Osaka (CanReCO).

BACKGROUND: The coronavirus disease 2019 (COVID-19) affected cancer care in Japan, but the detailed impact on cancer diagnosis and treatment is not well-understood. We aimed to assess the impact of COVID-19 on digestive cancer care in Osaka Prefecture, which has a population of 8.8 million. METHODS: We conducted a multi-center cohort study, using hospital-based cancer registry (HBCR) data linked to administrative data from 66 designated cancer care hospitals in Osaka. Records of patients diagnosed with cancer of the stomach, colorectum, esophagus, liver, gallbladder or pancreas were extracted from the HBCR data. Baseline characteristics, such as the number of diagnoses, routes to diagnosis and clinical stage, were compared between patients diagnosed in 2019 and those in 2020. We also compared treatment patterns such as the number of treatments (operations, endoscopic surgeries, chemotherapies, radiotherapies), pathological stage and time to treatment for each digestive cancer. RESULTS: In total, 62,609 eligible records were identified. The number of diagnoses decreased in 2020, ranging from -1.9% for pancreatic cancer to -12.7% for stomach cancer. Screen-detected cases decreased in stomach and colorectal cancer. The percentage of clinical stage III slightly increased across different cancers, although it was only significant for colorectal cancer. Among 52,741 records analyzed for treatment patterns, the relative decrease in radiotherapy was larger than for other treatments. The median time from diagnosis to operation was shortened by 2-5 days, which coincided with the decrease in operations. CONCLUSION: The impact of COVID-19 on cancer care in 2020 was relatively mild compared with other countries but was apparent in Osaka. Further investigation is needed to determine the most affected populations.

Trends in age-standardised net survival of stomach cancer by subsite and stage: A population-based study in Osaka, Japan, 2001-2014.

INTRODUCTION: The burden of stomach cancer remains high, particularly among Asian countries. Although Japan is known to achieve high survival from stomach cancer, little is known regarding the survival trends for recent years and survival by subsite and stage. We report age-standardised 1-, 3-, 5- and 10-year net survival for patients diagnosed with stomach cancer in Osaka, Japan. METHODS: We analysed patients diagnosed with primary stomach cancer and registered in the population-based cancer registry in Osaka Prefecture between 2001 and 2014. We used the non-parametric Pohar Perme method to derive net survival for each year. Both cohort and period approaches were used. Age was standardised using weights of the external population of the International Cancer Survival Standard. Multiple imputation was applied to handle missing information on subsite and stage before estimating age-standardised net survival by subsite (cardia and non-cardia) and stage (localised, regional and distant metastasis). We then examined general trends in the cohort-based survival estimates, as well as by subsite and stage, using linear regression. RESULTS: A total of 97,276 patients were included in the analysis. Age-standardised net survival improved steadily (mean annual absolute change ≥1.2%). Net survival for both subsites improved, but cardia cancer showed 7-23% lower survival than non-cardia cancer throughout the study period. Five-year net survival remained high (≥80%) in the localised stage from the beginning of this study. Net survival increased steeply (≥1.4% per year) in the regional stage. Although 1-year net survival increased by 14% in the distant stage, 5-year and 10-year net survival remained below 10%. CONCLUSION: Age-standardised net survival for stomach cancer in Japan improved during the study period owing to an increase in the number of patients with localised stage at diagnosis and improved treatment. Monitoring both short- and long-term survival should be continued as management of stomach cancer progresses.

Socioeconomic gaps over time in colorectal cancer survival in England: flexible parametric survival analysis.

BACKGROUND: Despite persistent reports of socioeconomic inequalities in colorectal cancer survival in England, the magnitude of survival differences has not been fully evaluated. METHODS: Patients diagnosed with colon cancer (n=68 169) and rectal cancer (n=38 267) in England (diagnosed between January 2010 and March 2013) were analysed as a retrospective cohort study using the National Cancer Registry data linked with other population-based healthcare records. The flexible parametric model incorporating time-varying covariates was used to assess the difference in excess hazard of death and in net survival between the most affluent and the most deprived groups over time. RESULTS: Survival analyses showed a clear pattern by deprivation. Hazard ratio of death was consistently higher in the most deprived group than the least deprived for both colon and rectal cancer, ranging from 1.08 to 1.17 depending on the model. On the net survival scale, the socioeconomic gap between the most and the least deprived groups reached approximately -4% at the maximum (-3.7%, 95% CI -1.6 to -5.7% in men, -3.6%, 95% CI -1.6 to -5.7% in women) in stages III for colon and approximately -2% (-2.3%, 95% CI -0.2 to -4.5% in men, -2.3%, 95% CI -0.2 to -4.3% in women) in stage II for rectal cancer at 3 years from diagnosis, after controlling for age, emergency presentation, receipt of resection and comorbidities. The gap was smaller in other stages and sites. For both cancers, patients with emergency presentation persistently had a higher excess hazard of death than those without emergency presentation. CONCLUSION: Survival disparities were profound particularly among patients in the stages, which benefit from appropriate and timely treatment. For the patients with emergency presentation, excess hazard of death remained high throughout three years from the diagnosis. Public health measures should be taken to reduce access inequalities to improve survival disparities.

Exploring socioeconomic differences in surgery and in time to elective surgery for colon cancer in England: Population-based study.

BACKGROUND: A persistent socioeconomic gap in colon cancer survival is observed in England. Provision of cancer care may also vary by socioeconomic status (SES). We investigated population-based data to explore differential surgical care by SES. METHODS: We analysed a retrospective cohort of patients diagnosed with colon cancer in England (2010-2013). We examined patterns of presentation and surgery by SES, and whether socioeconomic differences exist in the length of time from diagnosis to elective major resection using linear regression. RESULTS: Among a total of 68 169 patients with colon cancer, 21.0 % (3138/14 917) in the most affluent group had emergency presentation (EP) whereas 27.9 % (2901/10 386) in the most deprived. Among 45 332 (66.5 %) patients who underwent resection, the proportion of patients receiving urgent surgery (surgery before or ≤ 7 days of diagnosis) was higher in the most deprived group (39.9 %, 2685/6733) than the most affluent (35.4 %, 3595/10 146). Days from diagnosis to elective surgery (surgery > 7 days after diagnosis) ranged from 33.9 (95 % CI 33.1-34.8) in stage II to 38.2 (95 % CI 36.8-39.7) in stage I, but no socioeconomic differences in time were seen in all stages. CONCLUSIONS: Time to elective surgery for colon cancer did not differ by SES, whereas a higher proportion among deprived patients tended to be diagnosed through EP and to receive urgent surgery. These results suggest that the waiting time target may not be an appropriate measure to assess access to cancer care. Reducing both EP and urgent surgery should be a key policy target.

[Case of Hyperammonemia Induced by High-Dose Fluorouracil].

A case of hyperammonemia induced by chemotherapy, including high-dose fluorouracil(5-FU), for advanced unresectable large intestinal cancer has been reported. This case involved an 81-year-old female who was diagnosed with pT4bcN2M1 (multiple hepatic metastases; stage Ⅳ; KRAS: mutant)after emergency surgery for sigmoid colon cancer and diffuse peritonitis. Post-operation, the 4 courses of mFOLFOX6 plus Bmab therapy was started for advanced unresectable recurrent large intestinal cancer; 48 hours later, she developed consciousness disorder(JCS Ⅲ-300). The disorder promptly disappeared after discontinuation of high-dose 5-FU. Because high-dose 5-FU was inferred to be the main cause of hyperammonemia, XELOX plus Bmab therapy was started as a post-treatment. She did not develop hyperammonemia; therefore, 8 courses were administered. The patient is being followed-up now.

The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric Cancer.

The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma (EBVaGC), all tumor cells harbor the clonal EBV genome. The expression of latent EBV genes is strictly regulated through the methylation of EBV DNA. The methylation of viral DNA regulates the type of EBV latency, and methylation of the tumor suppressor genes is a key abnormality in EBVaGC. The methylation frequencies of several tumor suppressor genes and cell adhesion molecules are significantly higher in EBVaGC than in control cases. EBV-derived microRNAs repress translation from viral and host mRNAs. EBV regulates the expression of non-coding RNA in gastric carcinoma. With regard to the clinical application of demethylating agents against EBVaGC, we investigated the effects of decitabine against the EBVaGC cell lines. Decitabine inhibited the cell growth of EBVaGC cells. The promoter regions of p73 and Runt-related transcription factor 3(RUNX3) were demethylated, and their expression was upregulated by the treatment. We review the role of epigenetic regulation in the development and maintenance of EBVaGC and discuss the therapeutic application of DNA demethylating agents for EBVaGC.

Decitabine inhibits tumor cell proliferation and up-regulates e-cadherin expression in Epstein-Barr virus-associated gastric cancer.

The present study investigated the effect of a DNA demethylating agent, decitabine, against Epstein-Barr virus-associated gastric cancer (EBVaGC). Decitabine inhibited cell growth and induced G2/M arrest and apoptosis in EBVaGC cell lines. The expression of E-cadherin was up-regulated and cell motility was significantly inhibited in the cells treated with decitabine. The promoter regions of p73 and RUNX3 were demethylated, and their expression was up-regulated by decitabine. They enhanced the transcription of p21, which induced G2/M arrest and apoptosis through down-regulation of c-Myc. Decitabine also induced the expression of BZLF1 in SNU719. Induction of EBV lytic infection was an alternative way to cause apoptosis of the host cells. This study is the first report to reveal the effectiveness of a demethylating agent in inhibiting tumor cell proliferation and up-regulation of E-cadherin in EBVaGC. J. Med. Virol. 89:508-517, 2017. © 2016 Wiley Periodicals, Inc.

Image quality of a novel light-emitting diode (LED)-illuminated colonoscope.

BACKGROUND AND STUDY AIMS: Light-emitting diodes (LEDs) are used widely for their high luminous efficiency and durability. We developed a novel prototype high definition endoscope with white LEDs and evaluated the image quality it produced against a commercial endoscope with conventional light source. PATIENTS AND METHODS: The specifications of both colonoscopes were identical, except for the LED light source at the tip of the prototype. We examined 20 patients with rectal or sigmoid colon lesions and the image quality was evaluated in 40 images (one image from the LED colonoscope and one from the conventional colonoscope for each lesion) by three endoscopists. We additionally evaluated the 17 videos recorded with the LED colonoscope that were available. Image quality, mucosal and vascular color, and luminous distribution and intensity were scored on a 5-point scale. RESULTS: The mean score for vascular color given by one evaluator was significantly higher using the LED colonoscope than using the conventional colonoscope. The mean scores for mucosal color and luminous intensity from another evaluator were significantly lower with the LED colonoscope than with the conventional colonoscope. There were no significant differences in the luminous distribution scores for any of the evaluators. The image quality of the videos was evaluated as being similar with both colonoscopes. CONCLUSIONS: Image quality from the LED and conventional colonoscopes were similar, although the luminous intensity of the LEDs is inferior to that of the conventional light source at the present time.

Epstein-barr virus in gastric carcinoma.

The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation.

Assessment of reasons for referral and activities of hospital palliative care teams using a standard format: a multicenter 1000 case description.

CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES: The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS: This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS: We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

Endoscopic Resection is Infeasible for Early Gastric Cancers with Undifferentiated Components.

BACKGROUND/AIMS: Aim of this study is to find subgroup of early gastric cancer with lymph node metastasis for which successive further surgical operation is needed after endoscopic resection. METHODOLOGY: A total of 559 lesions of early gastric cancer, which had undergone curative gastrectomy, were enrolled in this study. We retrospectively investigated 10 clinicopathological factors predictive of lymph node metastasis by univariate and multivariate analysis. We showed the frequency of lymph node metastasis of subgroups in combination of independent factors selected by multivariate analysis. RESULTS: Lymph node metastases were detected in 57 lesions (10.2%). Univariate analysis revealed that lesion size > 30 mm, undifferentiated components, sm massive invasion, lymphatic invasion and venous invasion were factors significantly correlated with lymph node metastasis. By multivariate analysis, risk factors for lymph node metastasis were lesion size > 30 mm, undifferentiated components, sm massive invasion, and lymphatic invasion, with odds ratios of 2.17, 2.30, 5.88 and 8.24, respectively. In lesions with undifferentiated components, LNM were found in all subgroups. CONCLUSIONS: When we treat early gastric cancers contained undifferentiated components, even if they are predominantly differentiated-type intramucosal lesions, an additional surgical procedure should be considered or careful follow-up is required.

Identification of genes specifically methylated in Epstein-Barr virus-associated gastric carcinomas.

We studied the comprehensive DNA methylation status in the naturally derived gastric adenocarcinoma cell line SNU-719, which was infected with the Epstein-Barr virus (EBV) by methylated CpG island recovery on chip assay. To identify genes specifically methylated in EBV-associated gastric carcinomas (EBVaGC), we focused on seven genes, TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1, based on the results of methylated CpG island recovery on chip assay. We confirmed DNA methylation of the genes by methylation-specific PCR and bisulfite sequencing in SNU-719. The expression of the genes, except for BCL7A, was upregulated by a combination of 5-Aza-2'-deoxycytidine and trichostatin A treatment in SNU-719. After the treatment, unmethylated DNA became detectable in all seven genes by methylation-specific PCR. We verified DNA methylation of the genes in 75 primary gastric cancer tissues from 25 patients with EBVaGC and 50 EBV-negative patients who were controls. The methylation frequencies of TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1 were significantly higher in EBVaGC than in EBV-negative gastric carcinoma. We identified seven genes with promoter regions that were specifically methylated in EBVaGC. Inactivation of these genes may suppress their function as tumor suppressor genes or tumor-associated antigens and help to develop and maintain EBVaGC.