Diagnosis Of Multiple Cancers Research Articles

Association between rare pathogenic variants in established cancer risk genes and the diagnosis of single and multiple common cancers: A UK Biobank study.

10505 Background: Much of our understanding of cancer risk attributable to rare pathogenic variants (RPV) is derived from family-based and case-only cohort studies, which may be limited by ascertainment bias. We sought to identify associations between RPVs and cancer diagnoses in a large population-based study. Methods: We conducted a case-control study using the UK Biobank. We performed gene-based aggregate testing to examine the relationship between RPVs (defined as pathogenic or likely pathogenic variants) in 96 genes implicated in cancer risk and the diagnosis of 11 common cancers using the combined optimal unified sequence kernel association test (SKAT-O). Odds ratios (OR) and 95% confidence intervals (CI) were then calculated using Firth logistic regression. Results were adjusted for age, sex and genetic ancestry. Bonferroni-adjusted p-values were used to determine statistical significance. Variant pathogenicity was determined by American College of Medical Genetics criteria. Results: We identified 24 genes in which RPVs were statistically significantly associated with at least one of 11 common cancers among 183,626 individuals. The presence of an RPV in one of these 24 genes was associated with increased odds of one cancer (OR 1.8; 95% CI: 1.7-2.0), and multiple cancers (OR 2.5; 95% CI: 2.2-2.9). Conclusions: This large population-based study identified 24 established cancer risk genes in which RPVs were associated with common cancers. We identified both known and novel associations between cancer and RPVs. Some associations—i.e. renal/pancreas and MEN1—may be due to ascertainment and/or misclassification bias. We also show that individuals with RPVs in cancer risk genes not only have higher odds of one cancer diagnosis, but also multiple cancers.[Table: see text]

Chinese expert consensus: multidisciplinary diagnosis and treatment of multiple ground-glass nodule like lung cancer (2024 edition)

Multiple ground glass nodules (GGN) like lung cancer is a special type of synchronous multiple primary lung cancer, with two or more lesions present simultaneously. It has characteristics such as"indolent"development, less lymph node or distant metastasis, identical or different pathological stages, differential driving gene mutations, diverse imaging manifestations, and good prognosis. In order to standardize the diagnosis and treatment behavior of multiple GGN-like lung cancer, reduce issues such as over diagnosis and insufficient treatment, relevant domestic experts are organized by The Lung Cancer Medical Education Committee of the Chinese Medical Education Association, Lung Cancer Alliance of Chinese Thoracic Surgery, the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Tumor Ablation Expert Committee of the Chinese Society of Clinical Oncology, the Tumor Ablation Expert Group of the Chinese College of Interventionalists, The Chinese Expert Consensus:Multidisciplinary Diagnosis and Treatment of Multiple Ground-Glass Nodule Like Lung Cancer (2024 Edition) was discussed and formulated. The main content includes: follow-up strategies, differential diagnosis, diagnosis and staging, treatment methods, and post treatment follow-up for multiple GGN-like lung cancer.

Patient-recommended communication strategies to enhance clinical trial participation among Black people with cancer.

106 Background: People racialized as Black and/or African American (AA) represent less than 10% of participants enrolled in therapeutic cancer clinical trials that may improve cancer survival. AAs have higher cancer-related mortality rates but are less likely to be invited to participate in clinical trials compared to their white counterparts. We surveyed Black patients with cancer to assess their clinical trial discussion experiences and to identify opportunities to improve clinical trial participation. Methods: A purposive sample of 100 Black patients from a North Carolina Comprehensive Cancer Center were recruited to complete a survey between November 2021 and January 2023. Survey participants were identified through a clinical data warehouse and had to meet the following eligibility criteria: self-identified Black or AA race, diagnosis of either multiple myeloma, breast, prostate, colon, or lung cancer, and actively receiving or undergoing follow up cancer care. Surveys were conducted by a research assistant via phone. This analysis focused on those asked to participate in a clinical trial but declined participation. Results: All participants identified as Black or AA race with 2 participants additionally identifying as American Indian. Half of all surveyed participants were asked to participate in a clinical trial. Of those asked, 58% (n=29) declined and nearly half (n=12) indicated specific barriers that influenced their decision to not participate. Barriers included time constraints, distrust, fear of being harmed or being used as a guinea pig, not understanding the purpose of the study, and feeling rushed in their clinical trial decision making. All 29 participants were asked to select how they would prefer to receive clinical trial information and 97% selected speaking with their oncologist, 90% by video, 66% by internet and by a pamphlet or magazine, 52% at church and only 10% from a barber shop or salon. They also suggested simple and clear messaging about clinical trial opportunities, eligibility criteria, time commitment, taking time to discuss clinical trial options, and recruitment materials that can be taken home. Conclusions: Increasing participation in cancer clinical trials among Black patients with cancer necessitates careful discussion and consideration of fear, distrust, and system level barriers that influence the decision or capacity to enroll. Study recruitment should utilize patient centered communication tools that acknowledge the history of research exploitation in Black communities and clearly describe safety and security measures used in clinical trials.

Crohn’s disease-related anal fistula cancer diagnosed by examination under anesthesia: a case report

BackgroundAs the number of patients with inflammatory bowel disease (IBD) increases, the incidence of IBD-related colorectal cancer (CRC) is also on the rise. Crohn’s disease (CD)-related CRC has been reported to have a poorer prognosis than sporadic CRC, and the early detection of CD-related CRC is difficult. Japanese patients with CD are reported to have a higher frequency of anorectal cancer than the Western population; however, methods for early diagnosis have not yet been established because of perianal pain during the examination.Case presentationWe report a case of CD-related anal fistula cancer that was detected early by surveillance examination under anesthesia (EUA). The patient was a 37-year-old man, diagnosed with CD at the age of 15 years and started medical treatment. However, due to poor disease control, the intestinal tract remained highly inflamed and the patient continued to have over 10 bowel movements per day. He was referred to our hospital for surgical treatment after a colonoscopy (CS), which revealed multiple active ulcers and stenoses. Since three perianal seton drainage tubes had been placed around his anus since the age of 33 years, we decided to perform an EUA to rule out cancer coexistence in the anorectal region. After a random biopsy of the rectum by CS under general anesthesia, we resected and curetted multiple perianal fistulas as much as possible and reinserted the seton drainage tubes. Pathological examination of the fistula tract revealed adenocarcinoma in one tract, indicating the coexistence of anal fistula cancer. Based on the diagnosis of multiple intestinal stenoses and anal fistula cancer due to CD, we performed hand-assisted laparoscopic total colectomy, rectal amputation, extensive perineal resection, and reconstruction using a left rectus abdominis flap.ConclusionIn a long-term CD patient with anorectal lesions, we performed an EUA to diagnose the coexistence of anal fistula cancer at an early stage, and surgical resection was achieved. EUA is effective for the early detection and treatment of CD-related CRC and may contribute to an improved prognosis.

Difficulties of Diagnosing Primary Multiple Synchronous Breast Cancer with Histological Heterogeneity of Tumors (Clinical Case)

The difficulties of timely diagnosis of primary multiple synchronous breast cancer with histological heterogeneity of tumors are demonstrated by a clinical example. Taking into account the fact that breast cancer continues to lead among all oncological pathology and accounts for 11.8% of all malignant neoplasms, diagnostic algorithms of the stage should be personalized. The presented clinical case demonstrates multidisciplinary errors committed at different stages of the patient’s examination.

Case report: targeted sequencing improves the diagnosis of multiple synchronous lung cancers

Case report: targeted sequencing improves the diagnosis of multiple synchronous lung cancers

Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE−/− mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS.

Volume-Outcome Associations for Parathyroid Surgery in England

Previous studies have suggested an association between surgical volume and patient outcomes for parathyroid surgery. However, most previous studies are relatively small and the literature is dominated by studies form the US, which might not be readily generalizable to other settings. To investigate volume-outcome associations for parathyroid surgery in England. Cohort study that included all National Health Service hospital trusts in England with secondary analysis of administrative data using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Participants included all adult, elective hospital admissions for parathyroid surgery without a diagnosis of multiple endocrine neoplasia, parathyroid cancer, or kidney disease over a 5-year period (April 2014-March 2019 inclusive). The number of procedures conducted in the year prior to the index procedure by each surgeon and each hospital trust. Repeat parathyroid surgery within 1 year of the index procedure. This study included data for 17 494 participants who underwent parathyroidectomies conducted across 125 hospital trusts. The median (IQR) age of patients was 62 (53-71) years, and 13 826 were female (79.0%). Across the period, the number of surgeons conducting parathyroid surgery changed little (280 in 2014-2015 and 2018-2019), although the number of procedures conducted rose from 3331 to 3848 per annum. Repeat parathyroid surgery at 1 year was significantly associated with surgeon volume (odds ratio [OR], 0.99; 95% CI, 0.98-0.99), but not trust volume, in the previous 12 months. Extended length of stay (OR, 0.98; 95% CI, 0.98-0.99), hypoparathyroidism/calcium disorder (OR, 1.0; 95% CI, 0.99-1.0), and postprocedural complications (OR, 0.99; 95% CI, 0.99-1.0) were also associated with lower surgeon volume. In this cohort study, higher surgeon annual volume was associated with decreased rates of repeat parathyroid surgery. A minimum volume threshold of 20 procedures per annum should improve patient outcomes, although possible negative effects on access to services should be monitored.

Surgical volume-patient outcome relationships for parathyroidectomy in the England: analysis of an administrative dataset for the Getting It Right First Time programme

Abstract Introduction Previous studies suggest a relationship between surgical volume and patient outcomes for parathyroid surgery. However, most studies are small and from outside the UK. The aim of this study was to use Hospital Episodes Statistics to investigate volume-outcome relationships for parathyroid surgery in England. Methods We examined a five-year period (April 2014-March 2019 inclusive) for elective, adult admissions for surgery for primary hyperparathyroidism without a diagnosis of multiple endocrine neoplasia, parathyroid cancer or renal disease. Volume was the number of procedures conducted in the same financial year as the index procedure. The primary outcome measure was emergency readmission at 30 days or length of stay greater than 2 days which were taken to represent poorer outcomes. Results We included 17,498 parathyroidectomies. Across the period the number of surgeons conducting parathyroid surgery changed little (280 in 2014/15 and 2018/19), although the number of procedures conducted rose from 3,331 to 3,848 per annum. From the lowest surgeon volume category (1–10 per annum) to the highest (≥ 60 per annum) the proportion of patients readmitted at 30 days or with an extended length of stay decreased 11.7% to 7.0%, diagnosis of hypoparathyroidism within one year from 16.3% to 10.9%, repeat parathyroid procedures within one year from 2.5% to 1.0% and mortality rate at one year from 1.0% to 0.5%. These differences persisted after adjustment for demographic and procedural covariates. Conclusion Higher surgeon annual volume is associated with improved patient outcomes for parathyroid surgery. BAETS should consider recommending a minimum yearly workload.

Discrepancy Between Clinical Diagnosis and Whole-exome Sequencing-based Clonality Analysis of Synchronous Multiple Oral Cancers.

The definition of multiple oral cancers is based on the distances between the tumors. However, it is not possible to accurately predict tumor origins based only on clinical criteria. We performed whole-exome sequencing (WES) to analyze the genetic alterations in five tumors of two patients who underwent surgery in our hospital. In case 1, the distances between tumors on the right mandibular gingiva and buccal mucosa were more than 15 mm, leading to a clinical diagnosis of multiple primary tumors. WES revealed common mutations between tumors, suggesting that the tumors were derived from the same clone. In contrast, in case 2, the distance between tumors on the right side of the tongue was only 10 mm, but the tumors were diagnosed as double primary tumors because their mutations were completely different. WES, rather than the available clinical criteria, can clarify the clonal origins of multiple oral cancers.

Malignant phyllodes tumor in Lynch syndrome: a case report

BackgroundLynch syndrome, or hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic syndrome that predisposes individuals to multiple cancer types. The known cancers associated with Lynch syndrome include colorectal and endometrial cancers as well as cancers of the stomach, ovary, urinary tract, hepatobiliary tract, pancreas, small bowel, and brain. There are no searchable cases of malignant phyllodes of the breast associated with Lynch syndrome.Case presentationOur patient was a 43-year-old Caucasian woman who felt a lump in her left breast and was found to have a spindle cell neoplasm. Definitive surgery revealed a malignant phyllodes tumor. On the basis of her cancer diagnosis and family history of multiple cancers, a Myriad myRisk Hereditary Cancer® test panel of 25 genes was performed. This testing revealed that she had a heterozygous MSH6 mutation as part of the Lynch syndrome panel. Due to positive margins, the patient received adjuvant chemotherapy with doxorubicin and ifosfamide. She also had a subsequent total abdominal hysterectomy and a bilateral salpingo-oophorectomy for risk reduction. She remains in a high-risk surveillance program. Her family members have been tested, which revealed that her two brothers and daughter also carry the genetic mutation.ConclusionsThis case highlights the importance of genetic testing with rare malignancies because the full scope of phenotypic sequelae for known hereditary syndromes has not been mapped.

Quantitative determination of VEGF165 in cell culture medium by aptamer sandwich based chemiluminescence assay

In this work, we have developed a sensitive and selective chemiluminescence (CL) assay for vascular endothelial growth factor (VEGF165) quantitative detection based on two specific VEGF165 binding aptamers (Apt). VEGF is a predominant biomarker in cancer angiogenesis, and sensitive detection method of VEGF are highly demanded for both academic study and clinical diagnosis of multiple cancers. In our experiment, VEGF165 was captured in a sandwich structure assembled by two binding aptamers, one capture aptamer was immobilized on streptavidin-coated magnetic beads (MBs) and another VEGF-binding aptamer was labeled by biotin for further phosphatase conjunction. After Apt-VEGF-Apt sandwich was formed on MBs surface, alkaline phosphatase (ALP) was modified to the second aptamer to catalyze CL reaction. By applying 4-methoxy-4-(3-phosphatephenyl)-spiro-(1,2-dioxetane-3,2-adamantane) (AMPPD) as CL substrate, strong signal intensity was achieved. VEGF165 content as low as 1ng/mL was detected in standard spiked samples by our assay, and linear range of working curve was confirmed from 1 to 20ng/mL. Then our method was successfully applied for cell culture medium analysis and on-chip hypoxic HepG2-HUVEC co-culture model study with excellent accuracy equal to ELISA Kit. Our developed assay demonstrated an outstanding performance in VEGF165 quantification and may be further extended to clinical testing of important biomarkers as well as probing microchip cell culture model.

P1.06-045 Multiple Neoplasms Consist of Lung Cancer and Hematological Malignancies

The lung cancer is a cancer of the most in Japan and first place in cause of death. Lung cancer (LC)is still poor prognosis disease that cure only in early clinical stage. We report that we reviewed 55 cases of multiple neoplasms with lung cancer and the hematological malignancies. We intended for multiple neoplasms 339 cases including hematological malignancy. We reviewed 55 multiple neoplasms including the lung cancer. All patients were followed up until death or until August 2016. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. Definition of the multiple neoplasms in compliance with Warren & Gates. Also we determined the synchronous type and metachronous type in accordance with the definition of Moertel, so within less than 6 months was synchronous type, more than 6 months was metachronous type. All cases are 55 cases, consist of male 44 cases, female 11 cases, type of multiple neoplasms, synchronous type 14 cases, metachronous type 41 cases. Number of multiple neoplasms, double neoplasms 38 cases, triple neoplasms 14 cases, quadple neoplasms 3 cases. The median age was 71 years (range, 47-86 years) The counterpart of malignancies, MHL 26 cases, MDS 7 cases, AML 7 cases, HL 2 cases, MG 1 case, CLL 2 cases, CML 2 case, ALL 1 case, MGUS 3 cases. In double neoplasms, the median age of first diagnosis, 69 years, the second cancer were 71 years, about interval between lung cancer and hematological malignancies, lung cancer precedence case was 40M, hematological malignancy precedence case was 54M. The median overall survival was 24M. Diagnosis of LC within 5 years were 26 cases out of 41 cases. The important point is that 5 years are required for careful observation at the time of hematological malignancy diagnosis. We think that a prognosis is improved.

P2.03a-067 Therapy-Related Leukemia after Lung Cancer Chemotherapy: Topic: Clinical Trials

Therapy-related leukemia defined by the World health Organization 2008 classification scheme of hematolymphoid tumors including therapy-related acute myeloid neoplasms (t-AML), myelodysplastic syndrome (t-MDS). They occur as late complication of cytotoxic chemotherapy, radiation therapy and molecular target agents therapy against primary neoplasms. Recently, for lung cancer chemotherapy, new anti-cancer agent and molecular target agents are increased and more intensification chemotherapy performed. We report that we reviewed t-AML cases who survived from lung cancer and suffered t-AML. We intended for multiple neoplasms 339 cases including hematological malignancy. We reviewed 55 multiple neoplasms including the lung cancer. In 55 cases, second neoplasms that were t-AML cases were 4 cases, t-MDS case was 1 case. All patients were followed up until death or untile December 2015. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. We investigated cytogenetic abnormality, therapy, clinical outcome, prognosis, and cause of death. In 5 cases, 4 cases were diagnosed t-AML, 1 case was t-MDS. 5 of cases were 4 male and 1 female, primaly diagnosis were small cell carcinoma 2 cases, squamous carcinoma adenocarcinoma 3 cases. 1 case, One case (male case) was t-APL, he treated by all-trans retinoic acid and he reached complete response. T-M2 type, she treated by chemotherapy included daunorbicin and Ara-C (DC3-7), she did not achieve complete response. About prognosis, t-APL case, he lived 1 month after complete response, he died by lung cancer, t-AML cases, one female case, she lived 25 months after partial response, she died by t-AML relapse and refractory for salvage CTx. Other 3 cases, 1 case death by t-MDS, 2 cases death by t-AML. As the number of lung cancer survivors increased due to improvement in chemotherapy, clinician must more take attention of therapy-related leukemia and myelodysplastic syndrome by previous treatments.

Synchronous Diagnosis of Multiple Myeloma, Breast Cancer, and Monoclonal B-Cell Lymphocytosis on Initial Presentation.

The cooccurrence of more than one oncologic illness in a patient can present a diagnostic challenge. Here we report an unusual case of concomitant existence of multiple myeloma, breast cancer, and monoclonal B-cell lymphocytosis on initial presentation. The challenge was to accurately diagnose each disease and stage in order to maximize the therapeutic regimen to achieve cure/remission. Successful management of the patient and increased life expectancy can be achieved by multidisciplinary management and patient-oriented approach in multiple primary malignant synchronous tumors.

Ball valve syndromeを来した多発胃癌の1例

A 73-year-old man was referred to our department because of recurrent epigastralgia and nausea. Esophagogastroduodeno- scopy revealed a pedunculated tumor in the greater curvature of the middle body and drawn folds from the gastric body into the pyloric side. After pushing the scope, the protruding tumor was shifted aside and a good view was obtained. Another pedunculated tumor was evident in the greater curvature of the gastric angle. Computed tomography and gastrography with a barium meal revealed a tumor prolapsing in the duodenum. A diagnosis of multiple early gastric cancer with ball valve syndrome was made. Endoscopic submucosal dissection was performed. Histopathological examination revealed a poorly differentiated adenocarcinoma with an invasion depth of submucosa and lymph vessel permeation was positive. Therefore, the patient underwent a total gastrectomy. He is being followed up regularly.

Serum High Expression of Micorna-214 Is a Novel Predictor for Myeloma Bone Disease and Poor Prognosis

Abstract Background: Multiple myeloma (MM) originates from clonal expansion of malignant plasma cells in bone marrow, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs (miRNAs), such as miR-214, miR-34a and Mir-135 are reported to be involved in maintaining normal bone formation and development of metastatic bone lesions in cancers. Recent studies have demonstrated that miRNAs are stably expressed in human plasma and serum samples. And serum miRNAs have been used as biomarkers in diagnosis and prognosis of multiple cancers, including MM. However, the functional roles of miRNA in myeloma bone disease have not been elucidated yet. Materials and methods: In the present study, the serum miRNA expression was assessed from 152 samples including 108 MM samples and 44 healthy donors (HD) of serum. Microarray-based assay and real-time PCR was used to determine differentially expressed miRNAs. The correlation of miRNA expression and bone disease detected by whole body X-ray scanning was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Survival analysis was performed using the Kaplan-Meier method with a log-rank test and the generalized Wilcoxon procedure. Results: We performed serum miRNA profiles from 7 newly diagnosed MMs and 5 normal donors using a microarray-based assay. Our results identified that twenty-seven miRNAs which were reported to be involved in maintaining normal bone formation and development of bone lesions were significantly dysregulated, 4 miRNAs were significantly up-regulated and 23 miRNAs were significantly down-regulated in patient serum. We further performed real-time PCR to verify the expression of miR-214, miR-135, miR-132 and miR-92a in a large cohort of 108 MM patients and 44 healthy donors. We found that miR-214 (0.43±0.17 vs. 2.3±0.14, p<0.0001) and miR-135 (-0.13±0.08 vs. 1.84±0.13, p=0.0022) levels were significantly increased, while serum levels of miR-92a (-0.19±0.20 vs. -1.03±0.11, p=0.0023) were significantly decreased in MM patients. However, we did not found that miR-132 was obviously altered between normal and patient serum. Furthermore, serum levels of miR-214 and miR-135 were notably increased in the patients with lytic bone lesions compared to those without bone disease (both p<0.0001), and a positive correlation was observed between the expression levels of miR-214 (r=0.455, p<0.0001) and miR-135 (r=0.404, p<0.001) with grades of lytic bone lesions. Receiver operating characteristic (ROC) analysis revealed that serum levels of miR-214 and miR-135 can be used to distinguish bone disease in myeloma patients with area under the curve (AUC) > 0.7. Moreover, patients had a significantly shortened OS with high levels of circulating miR-214 (50.0 months vs. NR (not reached); p=0.039) or miR-135 (34.0 months vs.NR; p=0.041) versus those patients with down-regulated levels of miR-214 and miR-135. Patients with higher serum levels of miR-214 were responsible to bisphosphonates with extended OS (NR comparing to 26.0 months, p=0.029), suggesting that bisphosphonates is suitable to treat patients with high expression of circulating miR-214. Conclusion: Our findings reveal that the circulating miR-214 level is a biomarker for prediction of bone disease and prognosis in multiple myeloma. The detail mechanism how miR-214 involves in disease progression will be further explored. The result of this study also set the foundation for searching more circulating miRNA as biomarkers for metastatic bone lesions. Disclosures No relevant conflicts of interest to declare.

An aptamer targeting shared tumor-specific peptide antigen of MAGE-A3 in multiple cancers.

A DNA aptamer was identified against the shared tumor-specific MAGE-A3111-125 peptide antigen. The dissociation constant between the aptamer and the peptide was measured at 57 nM. Binding of the aptamer to seven types of cancer cells, melanoma, breast, colorectal, liver, lung, pancreas and oral cancer, was confirmed with flow cytometry and fluorescence imaging. Cy3-conjugated aptamers signals were specifically localized to the surface of those cancer cells. The results indicate that the DNA aptamer against the shared tumor-specific MAGE-A3 peptide can be used in cancer cell targeting and has the potential for developing into new modalities for the diagnosis of multiple cancers.

An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation

We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family.

P-125 Study of multiple neoplasms consist of hematological malignancies and gastrointestinal cancer

Introduction: Last decade, the treatment outcome of hematological malignancies were improved drastically. The case to become CR is not rare. Naturally, the long-term survivors increased, too. The long-term survivors increased at an opportunity to meet with second malignancies. So, we investigated multiple neoplasms including hematological malignancies and gastrointestinal cancer. Methods: In the case that hematologic malignancy was diagnosed in our hospital by 1988 from 2014. We intended for multiple neoplasms 303 cases including hematological malignancy. We reviewed 139 multiple neoplasms including hematological malignancies and gastrointestinal malignancies. All patients were followed up until death or until December 2014. Survival was measured from the diagnosis of multiple cancers to time of death or last contact. Definition of the multiple neoplasms was in compliance with Warren & Gates. Also we determined the synchronous type and metachronous type in accordance with the definition of Moertel, so within less than 6 months was synchronous type, more than 6 months was metachronous type. So we reviewed and reported about age, gender, kind of hematologic malignancies, kind of co-exist malignancies, and the cause of death. Results: All cases were 139 cases, gender was male 109 cases, female 30 cases, median age was 71 years (ranged 44-89 years). The number of malignancies, double cancer 111 cases, triple cancer 26 cases, quadruple cancer 2 cases, the style of multiple malignancies, metachronous pattern 96 cases, synchronous pattern 43 cases. The malignancies consist of multiple neoplasms, about gastrointestinal cancer, gastric cancer 72 cases, colon cancer 54 cases, lung cancer 7 cases, hepatocellular carcinoma 5 cases, esophageal cancer 16 cases, renal carcinoma 5 cases, pancreatic cancer 1 case, epipharyngeal cancer 1 case, prostate cancer 3 cases, breast cancer 1 case, urinary bladder cancer 1 case, Vater papillocarcinoma 1 case. About hematological malignancies, acute lymphoblastic leukemia 4 cases, acute myeloid leukemia 9 cases, chronic myeloid leukemia 8 cases, chronic lymphocytic leukemia 2 cases, myelodysplastic syndrome 23 cases, macroglobulinemia 6 cases, multiple myeloma 10 cases, monoclonal gammopathy undetermined significances 1 cases, solitary plasmacytoma 2 cases, malignant lymphoma unknown detail 1 case, Hodgkin's lymphoma 3 cases, non-Hodgkin's lymphoma 72 cases. The cases of hematological malignancies previously diagnosed were 37 cases, gastrointestinal cancer previously diagnosed were 59 cases. About metachronous type, interval time between hematological malignancies and gastrointestinal cancer, all cases (in 96 cases), 56 months, the 37 case that hematological malignancies previously diagnosed were 29 months, the 59 cases that gastrointestinal cancer previously diagnosed were 72 months. The death cases were 77 cases, about cause of death, due to hematological malignancies were 60 cases, due to gastrointestinal cancer 13 cases, due to other reason 4 cases. Conclusion: Multiple neoplasms occurred about 40% cases within 3 years, especially hematological malignancies previously diagnosed cases were about 57%, so the important point is that 3 years are required for careful observation at the time of hematological malignancy diagnosis. We think that a prognosis is improved.