Higher Tumor Incidence Research Articles

Abstract PD3-04: Classic lobular carcinoma in situ in the Netherlands: A population-based analysis

Abstract Background: Lobular carcinoma in situ (LCIS) is a non-invasive proliferation of epithelial cells of the terminal-duct lobular unit. Although LCIS is non-invasive itself, studies in the past showed that patients with LCIS have a 4-12 times higher risk of developing invasive breast cancer than the general population. Therefore, the optimal management of LCIS is still subject of debate. Despite lack of information about LCIS in the Dutch population, the Dutch guidelines recommend active surveillance for classic LCIS. This study aims to describe incidence and management of classic LCIS over time in the Netherlands, and to understand its behavior in terms of survival and the risk of developing subsequent ductal carcinoma in situ (DCIS) or invasive breast cancer. Methods: All female patients diagnosed with classic LCIS between 1989-2017 in the Netherlands were identified from the nationwide population-based Netherlands Cancer Registry. Patients previously diagnosed with DCIS or invasive breast cancer were excluded. Standardized incidence ratios (SIR) were calculated to estimate the risk of subsequent DCIS and invasive breast cancer, using data on population size from Statistics Netherlands (CBS). Multivariable Cox proportional hazards regression was performed to estimate hazard ratios (HR) of overall mortality and risk of subsequent invasive breast cancer for different patient-, tumor- and treatment-related characteristics. Competing risks were taken into account. Relative survival was estimated using the Ederer II method, with expected mortality of the general population (matched by age, gender, calendar year) as a reference. Results: We included 1,890 patients. The median age at diagnosis was 51 years (range 24-91 years). The incidence of classic LCIS increased from 186 patients between 1989-1993 to 497 patients between 2014-2017. Of all patients, 50.5% were treated with breast-conserving surgery, 10.2% were treated with mastectomy, 12.6% were treated with an unknown type of surgery and 26.7% did not receive surgery. While in 1989 all patients were surgically treated, only 41% were surgically treated in 2017. Radiotherapy was administered in 3.1% and endocrine therapy in 0.2% of the patients. Median follow-up to death, and subsequent DCIS or invasive breast cancer was 8.5 years (range 0-29 years) and 6.9 years (range 0-27 years). Unadjusted 10- and 20-year overall survival rates were 91% (95%CI:90-93%) and 76% (95%CI:73-79%). Unadjusted 10- and 20-year relative survival rates were 99% (95%CI:97-100%) and 95% (95%CI:91-99%). In total, 270 patients was diagnosed with subsequent invasive breast cancer and 48 were diagnosed with DCIS. Of these, 60% were ipsilateral and 40% were contralateral. The SIRs for DCIS and invasive breast cancer were 4.4 (95%CI:3.2-5.8) and 24.4 (95%CI:21.6-27.5) as compared to the general population, respectively. The SIR was higher for younger patients than for older patients, and the SIR of ipsilateral invasive breast cancer was higher in case no surgical management was performed. In multivariable analysis, increasing age was the most important predictor for overall mortality, while no surgical management was related to a higher incidence of subsequent invasive breast cancer. Conclusion: LCIS incidence has increased over time, while surgical management has decreased. This study shows that the mortality risk is very low compared to the general population. In contrast, the incidence of invasive breast cancer, over a median follow-up of 6.9 years (range 0-27 years), is over 24 times more common in LCIS patients than in the general population. These results suggest that LCIS patients have a good prognosis, even when a subsequent invasive breast cancer is diagnosed. However, the high incidence of second tumors suggest that we carefully monitor these patients. Citation Format: Marissa Corine van Maaren, Agustin Ortega Avila, Jos Bart, Pieter J Westenend, Sabine Siesling. Classic lobular carcinoma in situ in the Netherlands: A population-based analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-04.

Testicular tumors in prepubertal boys-organ preservation possible more often than expected

In prepubertal boys,testicular tumors are rare with an incidence between 2 and 5/million. In contrast to testicular tumors in adolescents and adults, more than 2/3of these tumors are benign. Unfortunately, in Germany in most cases, only malignant tumors (usually yolk sac tumors) are reported to the study center (MAKEIIV and nowV). Therefore, the incidence in Germany is unknown. Since the introduction of polychemotherapy in the 1970s, the prognosis of malignant testicular tumors has improved enormously and has become acurable disease, even in the case of recurrence. Today the orchiectomy, which was usually carried out in the past, appears to be no longer justified in most prepubertal boys due to the high incidence of benign tumors. It has been shown in various studies that organ-sparing surgery in germ cell tumors (epidermoid cysts, teratoma); gonadal stoma tumors (Sertoli, Leydig and granulosa cell tumors) and cystic lesions (intratesticular cysts and tubular ectasia of the rete testis) is reliable and safe. In cases with preoperative significantly increased AFP (caution: norm values not valid in the first year of life) and aclear testicular tumor in the ultrasound (yolk sac tumor) or if no testicular parenchyma is sonographically detectable, orchiectomy can still be carried out. Today orchiectomies in prepubertal boys should be an exception and the reasons for an orchiectomy must be well documented.

C20orf27 Promotes Cell Growth and Proliferation of Colorectal Cancer via the TGFβR-TAK1-NFĸB Pathway.

Background: Colorectal cancer (CRC) is a high incidence of malignant tumors that lacks highly effective and targeted drugs and thus it is in urgent need of finding new specific molecular targets. Methods and Results: In this study, by using WST-1 (Highly water-soluble tetrazolium salt-1) and colony formation assays, we found that C20orf27 (chromosome 20 open reading frame 27), a functionally unknown protein, enhanced the growth and proliferation of CRC cells. The nude mouse tumor formation experiments verified that C20orf27 promoted the growth of CRC. Signal pathway analysis identified the TGFβR-TAK1-NFĸB cascade as a mediator in C20orf27-induced CRC progression. Inhibition experiments using NFĸB inhibitors reversed this progression. Co-immunoprecipitation showed that C20orf27 promoted the activation of the TGFβR-TAK1-NFĸB pathway by interacting with PP1c (the catalytic subunit of type 1 phosphatase). Conclusions: Our results firstly characterized the functional role and molecular mechanism of C20orf27 in driving CRC growth and proliferation through the TGFβR-TAK1-NFĸB pathway, suggesting its potential as a novel CRC candidate therapeutic target and tumor marker.

RP-HPLC-ESI-IT Mass Spectrometry Reveals Significant Variations of the Human Salivary Protein Profile Associated with Predominantly Antibody Deficiencies.

Present study is designed to discover potential salivary biomarkers associated with predominantly antibody deficiencies, which include a large spectrum of disorders sharing failure of antibody production, and B cell defects resulting in recurrent infections, autoimmune and inflammatory manifestations, and tumor susceptibility. Understanding and clinical classification of these syndromes is still challenging. We carried out a study of human saliva based on liquid chromatography-mass spectrometry measurements of intact protein mass values. Salivary protein profiles of patients (n = 23) and healthy controls (n = 30) were compared. Patients exhibited lower abundance of α-defensins 1-4, cystatins S1 and S2, and higher abundance of glutathionylated cystatin B and cystatin SN than controls. Patients could be clustered in two groups on the basis of different levels of cystatin SN, S1 and S2, suggesting that these proteins may play different roles in the disease. Quantitative variations of these pro-inflammatory and antimicrobial peptides/proteins may be related to immunodeficiency and infectious condition of the patients. The high incidence of tumors in the group with the highest level of cystatin SN, which is recognized as tumoral marker, appeared an intriguing result deserving of future investigations. Data are available via ProteomeXchange with identifier PXD012688.

Metabolic syndrome and obesity as factors of good procnostic oncology in women in post-menopause with recent diagnosis of breast cancer

Objective: To evaluate the association between metabolic syndrome (MS), obesity, and central fat deposition with the immunohistochemical profile (IHC) of breast cancer (BC) in postmenopausal women. Methods: A comparative cross-sectional clinical study was carried out with 63 women with recent BC and MS, compared to 126 women with recent BC, without MS (control group). Inclusion criteria were: women aged 45-75 years, amenorrhea >12 months, without previous cancer treatment, attended at a University Hospital. The groups were matched for age, time since menopause, and body mass index (BMI), in the proportion of 1 case for 2 controls, according to the sample calculation of at least 186 women in their entirety. Clinical and anthropometric data were collected; tumor size and grade and the IHC profile (ER, PR, HER2, and Ki67). By IHC convention, tumors were grouped into five subtypes: Luminal A (ER+, PR+, HER-2 -, and Ki-67 <14%); Luminal B HER-2 - (ER+, PR+ or -, HER-2 -, and Ki-67≥14%); Luminal B HER-2+ (ER+, PR+ or -, HER-2+, and any Ki-67); Non-luminal HER-2 (ER-, PR-, HER2+, and any Ki-67); and Triple-negative (ER-, PR-, HER2-, and any Ki-67). Women with three or more diagnostic criteria were considered with MS: waist circumference (WC)>88 cm; TG≥150 mg/dL; HDL cholesterol<50 mg/dL; blood pressure ≥130/85 mmHg; glucose ≥100 mg/dL. For statistical analysis, the Student’s t-test, Gamma Distribution, χ2 test and logistic regression (odds ratio–OR) were used. Results: Among the participating women, the mean age, time since menopause and BMI were: 59.0±10.6 years, 11.4±9.6 years, and 28.5±5.5 kg/m2, respectively; there was no statistical difference in the comparison between the groups. Women with MS had a higher occurrence of tumors ≤2cm when compared to those without MS (49.2 vs. 31.8%, respectively) (p=0.038). Women with MS had a higher incidence of tumors with PR-positive (p=0.046), HER2-negative (p=0.038), when compared to women without MS (79.4 vs. 65.8% and 44.5 vs. 27.8%, respectively). In obese patients (BMI≥30 kg/m2), a higher proportion of HER2 negative tumors (p=0.047) was observed when compared to non-obese women (43.9 vs. 27.7%, respectively). In the multivariate analysis, a higher risk for tumors of the Luminal B HER-2 negative subtype was observed among women with MS (OR 2.00, 95%CI 1.03‒3.89), obese (OR 2.03, 95%CI 1.06‒3.90), and with central deposition of fat (OR 1.96, 95%CI 1.01‒4.03). Conclusion: Metabolic syndrome, obesity, and central fat deposition correlate with factors of good prognosis for breast cancer, such as tumors ≤2 cm, PR+ and HER2-, in postmenopausal women.

A retrospective survey on canine intracranial tumors between 2007 and 2017.

To clarify the prevalence of canine intracranial tumors in Japan, a retrospective study was performed using data on 186 canine intracranial tumors. Of 186 cases, 159 cases (85.5%) were primary and 27 cases (14.5%) were secondary intracranial tumors. Among primary intracranial tumors, meningioma (50.9%) was the most common, followed by glial tumors (21.4%) and primary intracranial histiocytic sarcoma (12.6%). These 3 tumors were most frequently found in middle-aged to elderly dogs without any sex predilection. Regarding glial tumors, the incidence of oligodendroglial tumors (79.4%) was higher than that of astrocytic tumors (17.6%). A significant breed predisposition (P<0.05) was observed for meningioma in Rough Collie, Golden Retriever, Miniature Schnauzer, and Scottish Terrier; for glial tumors in Bouvier de Flandres, French Bulldog, Newfoundland, Bulldog, and Boxer; for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi, Siberian Husky, and Miniature Schnauzer. The high incidence of oligodendroglial tumors in dogs and the breed predisposition for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi have not been reported in previous epidemiological studies on canine tumors. Since the incidence of intracranial tumors was vary among dog breeds, the present results demonstrate the uniqueness of the canine breed population in Japan.

Liver tumor segmentation based on 3D convolutional neural network with dual scale.

PurposeLiver is one of the organs with a high incidence of tumors in the human body. Malignant liver tumors seriously threaten human life and health. The difficulties of liver tumor segmentation from computed tomography (CT) image are: (a) The contrast between the liver tumors and healthy tissues in CT images is low and the boundary is blurred; (b) The image of liver tumor is complex and diversified in size, shape, and location.MethodsTo solve the above problems, this paper focused on the human liver and liver tumor segmentation algorithm based on convolutional neural network (CNN), and specially designed a three‐dimensional dual path multiscale convolutional neural network (TDP‐CNN). To balance the performance of segmentation and requirement of computational resources, the dual path was used in the network, then the feature maps from both paths were fused at the end of the paths. To refine the segmentation results, we used conditional random fields (CRF) to eliminate the false segmentation points in the segmentation results to improve the accuracy.ResultsIn the experiment, we used the public dataset liver tumor segmentation (LiTS) to analyze the segmentation results qualitatively and quantitatively. Ground truth segmentation of liver and liver tumor was manually labeled by an experienced radiologist. Quantitative metrics were Dice, Hausdorff distance, and average distance. For the segmentation results of liver tumor, Dice was 0.689, Hausdorff distance was 7.69, and the average distance was 1.07; for the segmentation results of the liver, Dice was 0.965, Hausdorff distance was 29.162, and the average distance was 0.197. Compared with other liver and liver tumor segmentation algorithms in Medical Image Computing and Intervention (MICCAI) 2017 competition, our method of liver segmentation ranked first, and liver tumor segmentation ranked second.ConclusionsThe experimental results showed that the proposed algorithm had good performance in both liver and liver tumor segmentation.

NIMG-51. THE CENTRALLY RESTRICTED DIFFUSION SIGN FOR DIFFERENTIATION BETWEEN TREATMENT-RELATED LESIONS AND TUMOR PROGRESSION IN GLIOMA PATIENTS: A VALIDATION STUDY

Abstract BACKGROUND The aim of the study was to compare the diagnostic accuracy of different diffusion patterns for differentiation between treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. METHODS A retrospective analysis of a prospective cohort was conducted. The images of 240 consecutive patients who underwent surgery for suspected glioma recurrence were reviewed for potential inclusion. Exclusion criteria were lack of a ring-enhancing lesion and presence of susceptibility artifact. Final diagnosis was established upon review of histopathology reports. Lesions showing treatment-related changes and less than 25% of viable tumor were considered treatment-related lesions. More than 25% of viable tumor was considered recurrent tumor. A neuroradiologist, blinded to the diagnosis, evaluated the diffusion patterns on preoperative MRI. ROC curve analysis was performed. RESULTS One hundred and ten patients were included (26 with treatment-related lesions and 84 with tumor progression). Of 110, 35 showed no reduced diffusion. Fifty patients had reduced diffusion in the solid lesion component (84%, recurrent tumor and 16%, treatment-related lesions). Twenty-five patients showed reduced diffusion within the central necrosis (48%, recurrent tumor and 52%, treatment-related lesions). Most cases with reduced diffusion in the central necrotic region showed mixed pathology with concurrent treatment effect and viable tumor. The AUC for the combined diffusion pattern (reduced diffusion in the solid lesion component vs in the necrotic region) was 0.68 (95%CI=0.55–0.81). The AUC for the traditional diffusion approach (reduced diffusion in the solid lesion component vs no reduced diffusion) was 0.59 (95%CI=0.49–070). No significant differences were found in AUC (p=0.3). CONCLUSION Although the existence of centrally reduced diffusion seems to be associated with the presence of treatment effect, it does not significantly increase the diagnostic accuracy of the traditional diffusion evaluation approach. This is most likely related to the high incidence of concurrent recurrent tumor and treatment effect.

Prospective molecular and morphological assessment of testicular prepubertal-type teratomas in postpubertal men.

In 2016, the World Health Organization classification system of testicular tumors included the new entity prepubertal-type teratoma based on its morphological and molecular profile, and the realization that these tumors may occur in postpubertal men. For treatment and prognostic purposes, it is important to distinguish prepubertal-type teratoma from the usual postpubertal-type teratoma, because the former is benign unlike the latter. The distinction may be challenging. In this study, we investigated clinical, morphological, and molecular criteria for distinguishing prepubertal-type teratoma from postpubertal-type teratoma in a prospective series of pure testicular teratomas. All cases of pure teratoma in postpubertal men assessed at Barts Health NHS Trust or in consultation since the introduction of routine investigation of chromosome 12p status in 2010 were reviewed. Morphological features suggestive of prepubertal-type teratoma were observed in 14 out of 35 cases. All underwent molecular testing and none displayed 12p amplification. Mean tumor size was 16 mm (range 7-28 mm). None had associated germ cell neoplasia in situ or significant atrophy. Four incorporated a well-differentiated neuroendocrine tumor, 1-2 mm in size. Of the ten patients with follow-up information, none have recurred or metastasized. Twenty-one of the 35 cases were diagnosed as postpubertal-type teratoma, mean tumor size 40 mm (range 6-90 mm). One case underwent molecular testing: a tumor of pure skeletal muscle differentiation and possessed 12p amplification. Three cases presented with clinical metastases. Eight cases contained immature areas, ten cases had associated germ cell neoplasia in situ, and 17 cases had severe atrophy of the parenchyma. One case with neither germ cell neoplasia in situ nor atrophy showed necrosis. We conclude that both morphological and molecular features are of help in differentiating prepubertal-type teratoma from postpubertal-type teratoma. In nearly all postpubertal-type teratomas, molecular testing was unnecessary, and merely confirmed the morphological impression in the prepubertal-type teratomas. Our study confirmed the high incidence of well-differentiated neuroendocrine tumors in the prepubertal-type.

Evidence for premature aging in a Drosophila model of Werner syndrome.

Werner syndrome (WS) is an autosomal recessive progeroid disease characterized by patients' early onset of aging, increased risk of cancer and other age-related pathologies. WS is caused by mutations in WRN, a RecQ helicase that has essential roles responding to DNA damage and preventing genomic instability. While human WRN has both an exonuclease and helicase domain, Drosophila WRNexo has high genetic and functional homology to only the exonuclease domain of WRN. Like WRN-deficient human cells, Drosophila WRNexo null mutants (WRNexoΔ) are sensitive to replication stress, demonstrating mechanistic similarities between these two models. Compared to age-matched wild-type controls, WRNexoΔ flies exhibit increased physiological signs of aging, such as shorter lifespans, higher tumor incidence, muscle degeneration, reduced climbing ability, altered behavior, and reduced locomotor activity. Interestingly, these effects are more pronounced in females suggesting sex-specific differences in the role of WRNexo in aging. This and future mechanistic studies will contribute to our knowledge in linking faulty DNA repair mechanisms with the process of aging.

Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis

Colon cancer is one of the first tumor types where a functional link between inflammation and tumor onset has been described; however, the microenvironmental cues affecting colon cancer progression are poorly understood. Here we demonstrate that the expression of the ECM molecule EMILIN-1 halts the development of AOM-DSS induced tumors. In fact, upon AOM-DSS treatment the Emilin1−/− (E1−/−) mice were characterized by a higher tumor incidence, bigger adenomas and less survival. Similar results were obtained with the E933A EMILIN-1 (E1-E933A) transgenic mouse model, expressing a mutant EMILIN-1 unable to interact with α4/α9β1 integrins. Interestingly, upon chronic treatment with DSS, E1−/− and E1-E933A mice were characterized by the presence of increased inflammatory infiltrates, higher colitis scores and more severe mucosal injury respect to the wild type (E1+/+) mice. Since alterations of the intestinal lymphatic network are a well-established feature of human inflammatory bowel disease and EMILIN-1 is a key structural element in the maintenance of the integrity of lymphatic vessels, we assessed the lymphatic vasculature in this context. The analyses revealed that both E1−/− and E1-E933A mice displayed a higher density of LYVE-1 positive vessels; however, their functionality was severely compromised after colitis induction. Taken together, these results suggest that the loss of EMILIN-1 expression may cause the reduction of the inflammatory resolution during colon cancer progression due to a decreased lymph flow and impaired inflammatory cell drainage.

Сравнительный анализ выполнения индикаторов региональных проектов «Борьба с онкологическими заболеваниями» на основании данных оперативного мониторинга за период январь-май 2018–2019 гг.

Malignant tumors are the problem of high social importance. High incidence, late diagnostic and high lethality of malignant tumors are factors that determine high significance of the oncological alertness aimed at disease detection and early treatment.

Impact of gestational low protein diet and postnatal bisphenol A exposure on chemically induced mammary carcinogenesis in female offspring rats.

This study evaluated the effect of gestational low protein diet (LPD) and/or postnatal bisphenol A (BPA) exposure on mammary gland development and carcinogenesis in female offspring. Pregnant Sprague-Dawley rats were fed a normal protein diet (NPD, 17% protein) or LPD (6% protein). At weaning, female offspring were distributed in four groups (NPD, LPD, NPD + BPA, and LPD + BPA) and received vehicle or BPA in drinking water (0.1%), during postnatal day (PND) 21 to 51. On PND 51, some female offspring were euthanized or received a single dose of 7,12-dimethylbenzoanthracene (DMBA, 30 mg/kg, i.g.) and were euthanized on PND 250. On PND 51, neither gestational LPD nor postnatal BPA exposure, individually or in combination, significantly altered the development of mammary gland tree, mean number of terminal structures or estrogen receptor beta (ER-β), proliferating cell nuclear antigen (PCNA) or caspase-3 protein expression in the mammary tissue. A significant reduction in mammary epithelial area (%) was observed in both LPD groups and a significant increase in ER-α protein expression was detected only in LPD group. In LPD + BPA group was observed a significant increase in both fat pad area (%) and in mean number of mammary epithelial cells positive for progesterone receptor (PR). On PND 250, the groups that received BPA presented lower latency and higher tumor incidence and tumor multiplicity and LPD + BPA group more aggressive tumors. These findings suggest that postnatal BPA exposure associated with gestational LPD is able to induce morphological changes in the mammary gland and increase susceptibility to mammary carcinogenesis.

Summary of the International Conference on Onco-Nephrology: an emerging field in medicine

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Synthesis and biodistribution of 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2-oxo-ethoxy-phenyl]-1,2-di- (p-hydroxyphenyl)but-1-ene for tumor imaging

The high incidence and mortality of breast cancer and other estrogen receptor related tumors motivates efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of treatments while concurrently and selectively delivering anticancer agents to the cancer tissues. In the present study, 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2-oxo-ethoxy-phenyl]-1,2-di-(p-hydroxyphenyl)but-1-ene was prepared and investigated as a potential agent for imaging estrogen receptors (ERs) in associated tumors. The compound was obtained in high radiochemical purity and radiochemical yields. The biodistribution of the radioactive compound in mature female rats showed an ER-mediation in the ovarian target tissues as the uptake was reduced by a blocking dose of estradiol. The nonspecific uptake in muscle was relatively low.

Bone tumours of the clavicle: Histopathological, anatomical and epidemiological analysis of 113 cases

BackroundThis retrospective study aimed to determine the frequency of bone tumours of the clavicle and their histopathological, anatomical and epidemiological characteristics in a large case series. MethodsThe records of 327 lesions of the clavicle collected from 1976 to 2018 in our bone tumour registry and institute of pathology were reviewed. Following data were evaluated: age, gender, side, radiological assessment, tumour location within the clavicle, and histopathological findings. ResultsBone tumours were detected in 113 patients with a mean age of 40 years. The lateral third of the clavicle was most frequently involved. Analysis revealed 22 benign, 31 intermediate, and 60 malignant tumours. Eosinophilic granuloma was the most commonly found neoplasm (18.6%), followed by bone metastases (15.0%), Plasma cell myeloma (8.8%), Ewing sarcoma (8.8%), and Osteosarcoma (8.0%). 53% of the tumours were malignant. Mean age was 51 years in the malignant tumour group and 28 years in patients with a benign/intermediate lesion (p < 0.001). ConclusionsThe high incidence of malignant bone tumours of the clavicle found in this study highlight the importance of biopsy to prevent delay in diagnosis and treatment of these lesions, especially in patients with increased age. We believe that the results of this study are of clinical importance and may aid the physician in the management of these rare lesions.

A Nationwide, Population-Based Epidemiologic Study of Childhood Brain Tumors in Korea, 2005-2014: A Comparison with United States Data.

We investigated the epidemiologic characteristics of childhood brain tumors (CBT) in Korea, and compared our findings with those from the United States. We searched the Korea National Cancer Incidence Database of the Korea Central Cancer Registry (KCCR) from 2005 to 2014, which included all Korean patients with CBT aged 0 to 19 years at diagnosis. The age-standardized incidence rates (ASR) and the 5-year relative survival rate (RSR) were determined. The Central Brain Tumor Registry of the United States (CBTRUS) classification and definitions were applied to allow direct comparison with U.S. A total of 6,027 CBTs were identified. The ASR of all CBTs was 5.08 per 100,000 population, which was significantly lower than that in the United States (5.57). However, the ASR of nonmalignant CBTs in Korea (2.48) was significantly higher than that in the United States (2.15). Embryonal tumors (ASR: 0.99 and 0.72 in the 0-4 and 5-9 year age groups, respectively) were the most common CBTs in these respective age groups. Germ cell tumors (0.78) and pituitary tumors (1.63) were the most common CBTs in the 10-14 and 15-19 year age groups, respectively. The 5-year RSR of CBTs was 84% and varied according to histology. High incidences of nonmalignant and germ cell tumors are distinct CBT features in Korean children and adolescents. To our knowledge, this is the first and largest population-based epidemiologic study of CBTs in Asia. Our findings support the notion that East Asian populations have a higher incidence of central nervous system germ cell tumors than other races.

A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord.

Adult T‐cell leukemia (ATL) is a mature T‐cell malignancy caused by human T‐cell leukemia virus type I infection, and 10%‐25% of patients show central nervous system (CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg‐PrkdcscidIl2rgtm1Wjl/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly (I.M.) at 5 weeks of age, 8 (80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously (S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV‐1‐specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV‐1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.

Precision medicine for gastrointestinal cancer: Recent progress and future perspective.

Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.

Germ Cell Tumors in Dysgenetic Gonads

This review describes the germ cell neoplasms that are malignant and most commonly associated with several types of gonadal dysgenesis. The most common neoplasm is gonadoblastoma, while others including dysgerminomas, yolk-sac tumors and teratomas are rare but can occur. The purpose of this review is to evaluate the incidences of these abnormalities and the circumstances surrounding these specific tumors.According to well-established methods, a PubMed systematic review was performed, to obtain relevant studies published in English and select those with the highest-quality data.Initially, the first search was performed using gonadal dysgenesis as the search term, resulting in 12,887 PubMed papers, published, from 1945 to 2017. A second search using ovarian germ cell tumors as the search term resulted in 10,473 papers, published from 1960 to 2017. Another search was performed in Medline, using germ cell neoplasia as the search term, and this search resulted in 7,560 papers that were published between 2003 to 2016, with 245 new papers assessing gonadoblastomas.The higher incidence of germ cell tumors in gonadal dysgenesis is associated with a chromosomal anomaly that leads to the absence of germ cells in these gonads and, consequently, a higher incidence of neoplasms when these tumors are located inside the abdomen. Several hypotheses suggest that increased incidence of germ cell tumors involves all or part of the Y chromosome or different genes.