Etiology Of Tumors Research Articles

Association of Anti-Mullerian Hormone, Follicle-Stimulating Hormone, and Inhibin B with Risk of Ovarian Cancer in the Janus Serum Bank.

Reproductive factors, including parity, breastfeeding, and contraceptive use, affect lifetime ovulatory cycles and cumulative exposure to gonadotropins and are associated with ovarian cancer. To understand the role of ovulation-regulating hormones in the etiology of ovarian cancer, we prospectively analyzed the association of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B with ovarian cancer risk. Our study included 370 women from the Janus Serum Bank, including 54 type I and 82 type II invasive epithelial ovarian cancers, 49 borderline tumors, and 185 age-matched controls. We used conditional logistic regression to assess the relationship between hormones and risk of ovarian cancer overall and by subtype (types I and II). Inhibin B was associated with increased risk of ovarian cancer overall [OR, 1.97; 95% confidence interval (CI), 1.14-3.39; P trend = 0.05] and with type I ovarian (OR, 3.10; 95% CI, 1.04-9.23; P trend = 0.06). FSH was not associated with ovarian cancer risk overall, but higher FSH was associated with type II ovarian cancers (OR, 2.78; 95% CI, 1.05-7.38). AMH was not associated with ovarian cancer risk. FSH and inhibin B may be associated with increased risk in different ovarian cancer subtypes, suggesting that gonadotropin exposure may influence risk of ovarian cancer differently across subtypes. Associations between prospectively collected AMH, FSH, and inhibin B levels with risk of ovarian cancer provide novel insight on the influence of premenopausal markers of ovarian reserve and gonadotropin signaling. Heterogeneity of inhibin B and FSH effects in different tumor types may be informative of tumor etiology.

Abstract P2-20-07: Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience

Abstract Background Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein metastatic disease invades the meninges of the central nervous system via contiguous spread from bone or brain metastases or hematogenous spread from systemic disease. Breast cancer is the most common solid tumor etiology of LMC. Approximately 5% of patients (pts) with breast cancer develop LMC. LMC has a median survival of 4 weeks when untreated and 8-16 weeks with treatment. The diagnosis of LMC remains challenging with only 60% of pts having cerebrospinal fluid (CSF) positive for malignant cells. There is no generally accepted standard of care for treatment of LMC but it may involve intrathecal or systemic chemotherapy, whole brain or spinal radiotherapy, or a combination of modalities. We aimed to assess detection and treatment strategies of LMC in pts with breast cancer treated at the Ohio State University Comprehensive Cancer Center-James (OSUCCC-James) to better characterize the disease and guide clinical care. Methods An IRB-approved single-institution retrospective protocol was developed. Medical records of 469 pts who had undergone a procedure related to LMC diagnosis or treatment were identified and reviewed to determine study eligibility. Comprehensive data was obtained through information warehouse and chart review was performed for the eligible 69 pts with breast cancer diagnosed with LMC and treated at the OSUCCC-James between January 1, 2005 and December 31, 2015. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan Meier methods. Comparisons in OS between groups were analyzed using Log-rank tests. Results Sixty-nine female pts were included in the analysis with the following characteristics: median age 55.7 years (range: 48-60.6 years), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (86%; N=59), and Caucasian (78%; N=54). They had the following subtypes hormone receptor positive (HR +), and human epidermal growth factor receptor (HER2) negative (61%, N=42), triple negative (25%, N=17) and HER2 positive (10%, N=7). The most common sites of metastases included bone (42%), brain (28%), and lung (12%). The median time between the diagnosis of first metastasis and LMC was 0.9 years (range: 0-3.2 years). Of the 40 (58%) pts who underwent lumbar puncture, 21 (52%) pts had positive CSF cytology. Sixty-eight pts (99%) had MRI findings suggestive of LMC. The most common treatment modalities were systemic chemotherapy (N=14, 41%), radiotherapy (N=12, 35%), and intrathecal chemotherapy (N=14, 35%). Fifty-six pts (81%) had a change in systemic chemotherapy agent after diagnosis. The median OS of all pts was 2.4 months (95% confidence interval: 1.2-4.4). Pts with ER+/PR+/HER2- had a better OS (4.4 months, 95%CI 1.5, 6.1)) compared to those with HER2+ (1.3 months, 95%CI 0.2, 1.9) or ER-/PR-/HER2- (0.6 months, 95%CI 0.0, 15.8) subtypes (p-value=0.004). Pts with negative CSF cytology had a greater OS compared to those with positive CSF cytology (9.8 vs. 0.7 months, p=0.026) and pts who had a change in systemic treatment had a greater OS compared with patients who had no new treatment (2.5 months vs. 1.2 months, p =0.039). No significant difference was seen in OS between ECOG performance status groups. Conclusions LMC is a relatively rare yet devastating complication of breast cancer. Based on our institutional experience, LMC remains a clinical challenge and is associated with poor OS. Pts with triple negative and HER2 positive disease and those with high disease burden fare worse. Pts who had change in systemic therapy fare better. Dedicated clinical trials are urgently needed to improve outcomes. Citation Format: Hannah Rinehardt, Nicole Williams, Evan Morgan, Mahmooud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Vinay Puduvalli, Pierre Giglio, Maryam Lustberg, Robert Wesolowski, Sagar Sardesai, Daniel Stover, Jeffrey VanDeusen, Jose Bazan, Bhuvaneswari Ramswamy, Anne Noonan. Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience [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 P2-20-07.

Determination of Causative Human Papillomavirus Type in Tissue Specimens of Common Warts Based on Estimated Viral Loads.

Background: Assessment of human papillomavirus (HPV) type-specific viral load (VL) is a valid tool for determining the etiology of HPV-related skin tumors, especially when more than one HPV type is detected within one lesion.Methods: The causative HPV type was determined in 185 fresh-frozen tissue specimens of histologically confirmed common warts (CWs) collected from 121 immunocompetent patients. All tissues were tested using the type-specific quantitative real-time polymerase chain reactions (PCR) for the most common wart-associated Alpha-PV (HPV2/27/57) and Mu-PV types (HPV1/63/204). The presence of 23 additional low-risk HPVs was evaluated using a conventional wide-spectrum PCR.Results: HPV DNA was detected in 176/185 (95.1%) CWs and multiple HPV types in 71/185 (38.4%) lesions. Using the VL approach and a robust cutoff of one viral copy/cell established in this study, HPV2/27/57 were determined as causative agents in 41/53 (77.3%) and 53/71 (74.7%) CWs with single and multiple HPVs, respectively.Conclusions: CWs are mostly etiologically associated with HPV2/27/57 and only rarely with HPV1. In the majority of CWs containing multiple HPVs, a single HPV type was present in high concentration, indicating etiological association. No significant differences in VLs of lesion-causing HPV types in CWs containing single or multiple HPVs were found.

Diagnostic yield and technical aspects of fluoroscopy-guided percutaneous transpedicular biopsy of the spine: A single-center retrospective analysis of outcomes and review of the literature.

Background:The technique of a percutaneous transpedicular biopsy of spinal lesions has been shown to be a useful alternative to paraspinal biopsy for vertebral body lesions in the thoracic and lumbosacral spine. Percutaneous vertebral biopsy is less invasive, cost-effective, and is suitable for patients with intractable back pain and vertebral body lesions that are detected with noninvasive imaging modalities.Objective:The purpose of this study was to establish the diagnostic utility and spectrum of fluoroscopy-guided percutaneous transpedicular biopsies of the thoracolumbar spine performed at our institution.Materials and Methods:This retrospective descriptive study to establish the diagnostic utility and spectrum of percutaneous fluroscopic guided transpedicular biopsy of lower thoracic and lumbar vertebral lesions has been performed on 42 patients in a tertiary care hospital between April 2017 and December 2019. There were 28 male patients and 14 female patients. The mean age was 48 years (range: 12–66 years). There were one 14 thoracic, 26 lumbar, and 2 sacral biopsy specimens. The lesion level was determined under fluoroscopy. Biopsy was taken with a trephine needle under local anesthesia. Accuracy and effectiveness of the technique were analyzed on histopathologic confirmation.Results:The fluoroscopic guided percutaneous transpedicular spine biopsies of 42 patients with spinal pathology were performed through the posterior transpedicular approach percutaneously. Of the 42 patients, 28 were male (66.7%) and 14 were female (33.3%). Vertebral involvement was observed to be more in the lower thoracic region (26.2%), followed by the upper dorsal region (7.1%), L1 (23.6%), L2 (6.4%), L3 (14.6%), L5 (17.3%), and sacrum (4.8%). There were 21 cases with tumor etiology (14 metastasis, 2 malignant round cell tumor, 2 multiple myeloma, and 3 lymphomas), 14 tuberculosis (TB), 4 osteomyelitis, 2 inflammatory, and 1 isolated compression fractures. Twelve patients of the 14 diagnosed cases who were diagnosed with TB on histopathology had positive TB culture and sensitivity pattern.Conclusion:Percutaneous transpedicular fluoroscopy-guided biopsy with a Jamshidi trocar with an internal diameter of 3.1 mm is a simple, safe, and reliable method for the etiological diagnosis of vertebral lesions. The use of this technique, however, is dependent on the accurate placement of the trocar and on close qualified interdisciplinary clinical cooperation. This minimally invasive technique is simple, safe, and effective in the diagnosis of malignant and infective lesions.

Efficacy and safety of uracil-tegafur in patients with recurrent or metastatic thymic carcinoma

Background: Thymic carcinoma (TC) is a rare but aggressive thymic epithelial neoplasm, with lymphoepithelioma-like histological features resembling nasopharyngeal carcinoma. Epstein–Barr virus is a known etiology of various tumors, including nasopharyngeal carcinoma, in Asian patients. These patients have a significant response to cisplatin plus 5-fluorouracil (5-FU) combination chemotherapy. Interestingly, this regimen seems to be effective for TC s resembling nasopharyngeal carcinoma. Currently, the standard second-line therapy for advanced TC is uncertain. The use of uracil-tegafur (UFT), a combination of uracil and 5-FU prodrug, has not been reported in literature. We analyzed the effectiveness and toxicity of UFT as an optional regimen for recurrent or metastatic TC. Materials and Methods: This retrospective study enrolled patients verified to have recurrent or metastatic TC and who were treated with UFT between 2017 and 2019 in our hospital. All patients were treated with UFT until disease progression, the patients could no longer tolerate the treatment, or patient refusal. We assessed the safety and efficacy of UFT for TC. Results: Four patients were female and seven were male. The age ranged from 41 to 77 years. The histological features of TC were squamous cell carcinoma and poorly differentiated carcinomas. Grade 3 toxicity occurred in one patient. No treatment-related deaths were observed. Among the 11 patients, 6, 2, and 3 had a partial response, stable disease, and progressive disease, respectively. The objective response rate was 54.5%. The median progression-free survival and overall survival of patients who received UFT chemotherapy were 8.16 months (95% confidence interval [CI]: 0.76–15.56 months) and 19.43 months (95% CI: 17.07–21.78 months), respectively. Conclusion: Single-agent UFT seems to have potential effectiveness and good tolerability in patients with recurrent or advanced TC.

The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation.

The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation. From chronic intestinal inflammation to cancer development, it involves signal transducers and activators of transcription (STAT)3 activation. STAT3 activates by the interaction between epithelial cells and BFT. Thus, regulatory T-cell (Tregs) will activates and reduce interleukin (IL)-2 amount. As the level of IL-2 drops, T-helper (Th17) cells are generated leading to increase in IL-17 levels. IL-17 is implicated in early intestinal inflammation and promotes cancer cell survival and proliferation and consequently triggers IL-6 production that activate STAT3 pathway. Additionally, BFT degrades E-cadherin, hence alteration of signalling pathways can upregulate spermine oxidase leading to cell morphology and promote carcinogenesis and irreversible DNA damage. Patient with familial adenomatous polyposis (FAP) disease displays a high level of tumour load in the colon. This disease is caused by germline mutation of the adenomatous polyposis coli (APC) gene that increases bacterial adherence to the mucosa layer. Mutated-APC gene genotype with ETBF increases the chances of CRC development. Therefore, the colonisation of the ETBF in the intestinal tract depicts tumour aetiology can result in risk of hostility and effect on human health.

Breast cancer animal models and applications.

Breast cancer is the most common malignancy in women. Basic and translational breast cancer research relies heavily on experimental animal models. Ideally, such models for breast cancer should have commonality with human breast cancer in terms of tumor etiology, biological behavior, pathology, and response to therapeutics. This review introduces current progress in different breast cancer experimental animal models and analyzes their characteristics, advantages, disadvantages, and potential applications. Finally, we propose future research directions for breast cancer animal models.

Diagnostic utility of CT for small bowel obstruction: Systematic review and meta-analysis.

BackgroundTo perform a systematic review and meta-analysis evaluating the diagnostic performance of computed tomography (CT) for small bowel obstruction (SBO), including diagnostic accuracy, ischemia, predicting surgical intervention, etiology and transition point.MethodsPubMed/MEDLINE and related databases were searched for research articles published from their inception through August 2018. Findings were pooled using bivariate random-effects and summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, patient age, enhanced CT, slice thickness and pathogenesis affected classification accuracy.ResultsIn total, 45 studies with a total of 4004 patients were included in the analysis. The pooled sensitivity and specificity of CT for SBO were 91% (95% confidence interval [CI]: 84%, 95%) and 89% (95% CI: 81%, 94%), respectively, and there were no differences in the subgroup analyses of age, publication year, enhanced CT and slice thickness. For ischemia, the pooled sensitivity and specificity was 82% (95% CI: 67%, 91%) and 92% (95% CI: 86%, 95%), respectively. No difference was found between enhanced and unenhanced CT based on subgroup analysis; however, high sensitivity was found in adhesive SBO compared with routine causes (96% vs. 78%, P = 0.03). The pooled sensitivity and specificity for predicting surgical intervention were 87% and 73%, respectively. The accuracy for etiology of adhesions, hernia and tumor was 95%, 70% and 82%, respectively. In addition, the pooled sensitivity and specificity for transition point was 92% and 77%, respectively.ConclusionsCT has considerable accuracy in diagnosis of SBO, ischemia, predicting surgical intervention, etiology and transition point.

Biliary decompression in patients with obstructive jaundice

Aim. Evaluation of the biliary tract decompression methods and their use results, in patients with obstructive jaundice of various etiologies on the basis of our own clinical material.Material and Methods. A retrospective analysis of the biliary tract drain results in 6935 patients with obstructive jaundice with benign and tumor etiology. In 87% cases there was B Class of obstructive jaundice. In 93% we observed mild (A Class) obstructive jaundice. For the biliary tract drainage we used laparoscopic or open surgical access. The retrograde drain we used in sixty-seven percent cases with obstructive jaundice B Class. In sixty-six percent cases of obstructive jaundice C Class, we used antegrade drain.Results. The biliary decompression was effective in 98%. Regarding the rate and timing of bilirubin reduction, all the applied methods showed a similar result, however, the greatest number of complications and fatalities we recorded in patients after antegrade percutaneous drain of the biliary tract and transabdominal access. In 36% the performed interventions became the final treatment option, and the sixty-one percent of patients underwent two-stage treatment. The overall mortality rate was 3%.Conclusion. The use of percutaneous drainage is justified for obstructive jaundice with tumor origin, and possible radical surgical treatment. Transabdominal access drainage for benign etiology of obstructive jaundice in compensated patients can be safely used. Transduodenal endoscopic drain is an alternative to other methods biliary tract drain in severe and medium obstructive jaundice of benign etiology. The same drain method can be used for drainage of biliary tract in patients with tumors of the hepatopancreatobiliary zone organs, as a palliative treatment.

Desmoid tumor initially unresectable – About two cases

Desmoid tumor, also called aggressive fibromatosis, is a rare fibroblastic proliferation of connective tissue and skeletal muscle aponeurosis. The aetiology of desmoid tumours is poorly understood, but they have been related with oestrogen stimuli, previous trauma, surgical interventions and pregnancy. Although it is characterized by not having potential for metastasize or differentiate, it is a non-encapsulated lesion, with an infiltrative growth and unpredictable behaviour. In this way, it could have either an aggressive pattern, when compared with other low degree malignancy sarcomas, or a very indolent one, even with spontaneous regression. Therapeutic options in desmoid tumours have been changing over these last years, as surgery upfront in asymptomatic patients has been superseded by active surveillance. However, treatment has to be individualized in some specific scenarios such as intra-abdominal lesions. We present two cases of patients diagnosed with an intra-abdominal desmoid tumour with threatening behaviour, the treatment approach and final resolution.

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

Breast cancer is a malignant tumor in groups of cancer cells that may develop into (invade) or spread to distant body regions around tissues. In both advanced and developing nations and in many parts of the globe, the burden of breast cancer is rising. It's the most prevalent malicious person illness in females, with 18% of all female cancers and the third most prevalent cause of cancer death globally. This case-control study was organized to explore the potential role of chosen genetic parameters in the Al-Diwanyia province in random samples of breast cancer patients the research, 5 ml of blood samples from 50 women with post-operative breast cancer attending the outpatient oncology department at Al Diwaniyia Teaching Hospital were employed compared to 50 women without cancer, patient ages and control ranged from 18 to 80 years. Among the three susceptibility genes studied, BRCA In BRCA-1 GG genotype evidently proposed a risk factor for tumor as had an (OR 5.3191) and risk factor (EF 0.065); AG & AA genotypes, on the other hand, played a rather preventive part as they had no risk factor (PF) of 0.0476 & 0.1667 respectively and low OR (0.7619 & 0.7917 respectively) and patients had 16%, and 84% of patients had G and A alleles respectively. The genotype of BRCA-2 AG As had the risk factor (OR 13.4146) and the risk factor (EF 0.1851), the AA genotype, on the other hand, did not have a risk factor role since it had a protective fraction (PF) of 0.9103 and a low OR (0.0731). Patients have 10% of G and 90% of A alleles compared to 100% of A only. In the P53 CC genotype, tumor etiology has evidently been proposed, as was the case with (OR 1.2941) and risk factor (EF 0.091). The GC genotype, on the other hand, did not have a risk factor as it had (PF) of 0.087 and low OR (0.4565) and patients had 56 percent of G allele and 44 percent of C allele compared to 52 percent of G and 48 percent of C control.

Replication of GWAS identifies RTEL1, CDKN2A/B, and PHLDB1 SNPs as risk factors in Portuguese gliomas patients.

Diffuse gliomas are the most common malignant primary brain tumors and remain incurable. A better knowledge of the tumor etiology is required. Specific single nucleotides polymorphisms (SNPs) rs4977756 (CDKN2A/B), rs6010620 (RTEL1), rs498872 (PHLDB1), rs2736100 (TERT), and rs4295627 (CCDC26) have been associated with glioma susceptibility and are potential risk biomarkers. This study aimed to analyze five SNPs associated with glioma susceptibility, in the Portuguese population. SNPs were genotyped using the Sequenom MassARRAY platform in 127 gliomas and 180 controls. Unconditional logistic regression models were used to calculate odds ratio (OR) and 95% confidence intervals. The false-positive report probability was also assessed. The associations between polymorphisms and survival were evaluated using the log-rank test. It was found that the AG and GG genotypes of the rs4977756 (CDKN2A/B) were associated with an increased risk of gliomas (OR 1.85 and OR 2.38) and glioblastomas (OR 2.77 and OR 3.94). The GA genotype of the rs6010620 (RTEL1) was associated with a decreased risk of glioblastomas (OR 0.45). We also observed that the GA genotype of the rs498872 (PHLDB1) was associated with an increased risk of gliomas (OR 2.92) and glioblastomas (OR 2.39). No significant risk associations were found for the rs2736100 (TERT) and rs4295627 (CCDC26). In addition, the genotype AA of the rs498872 (PHLDB1) was associated with poor overall survival of gliomas patients (AA vs. GA, p = 0.037). The rs6010620 (RTEL1), rs4977756 (CDKN2A/B), and rs498872 (PHLDB1) are associated with glioma risk in the Portuguese population and these data may contribute to understanding gliomas etiology.

Brain tumor disparities: From biology to social determinants - The 2019 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that fosters international and interdisciplinary collaborations focusing on research related to the etiology, outcomes, and prevention of brain tumors. The 20th annual BTEC meeting with the theme "Brain tumor Disparities: From Biology to Social Determinants" was held in Los Angeles, CA, USA, on June 6-8, 2019. Scientists from the United States and Europe representing a broad range of brain tumor research disciplines presented their research findings at the meeting. The scientific content of the meeting is summarized below.

The Tumoral Etiology of the Superior Cava Vein Syndrome Presenting as Exsudative Pericarditis in a Young Patient

Abstract We present the case of a 36-year-old patient admitted with dyspnea, subjective sensation of edema of the cervical region, and precordial pain with sudden onset. Pathological antecedents revealed a respiratory intercourse three weeks ago. Laboratory findings indicated an inflammatory syndrome accompanied by hypoproteinemia. We performed an echocardiographic examination which revealed important pericardial effusion and swinging heart aspect with diastolic collapse of the right atrium and ventricle. According to the existing guidelines pericardiocentesis was immediately required. The hemorrhagic pericardial effusion had an intense positive Rivalta reaction with frequent macrophages and malignant atypical cells. The next step was a full-body computer tomography scan, which revealed an expansive mediastinal mass, invading the upper cava vein and pericardium, with mediastinal adenopathy. A biopsy was performed and the pathology examination concluded there was a classical Hodgkin’s lymphoma nodular sclerosis type. Finally the patient was directed to oncology department.

Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study.

Limited data exist on the burden and features of non-cirrhotic hepatocellular carcinoma (HCC) in the United States. To evaluate characteristics, aetiologies, trends and outcomes of non-cirrhotic HCC from 2000 to 2014 at five large US centres METHODS: Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non-cirrhotic patients were older (64.1 vs 61.2years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P<.001 for all). Among non-cirrhotic patients, non-alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non-cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P<.0001]) and NAFLD (0.66% [P=.003]). Patients with non-cirrhotic HCC had larger tumours (8.9 vs 5.3cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P<.001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3years, P=.004). Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non-cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non-cirrhotic patients presented with more advanced HCC, their survival was better.

GCT-25 - The avian embryo as a new patient-derived xenograft model to explore germ cell tumour aetiology, heterogeneity and therapeutic screening

GCT-25 - The avian embryo as a new patient-derived xenograft model to explore germ cell tumour aetiology, heterogeneity and therapeutic screening

Metallic air pollutants and breast cancer heterogeneity

BackgroundEmerging evidence suggests airborne metals may be associated with breast cancer risk. However, breast cancer is heterogenous and associations with heavy metals vary by subtype. Heavy metals possess both carcinogenic and xenoestrogenic properties which may be related to different tumor etiologies. Therefore, we tested for etiologic heterogeneity, using a case-series approach, to determine whether associations between residential airborne metal concentrations and breast cancer differed by tumor subtype. MethodsBetween 2005 and 2008, we enrolled incident breast cancer cases into the Breast Cancer Care in Chicago study. Tumor estrogen and progesterone receptors status was determined by medical record abstraction and confirmed immunohistochemically (N = 696; 147 ER/PR-negative). The 2002 USEPA's National Air Toxics Assessment census-tract estimates of metal concentrations (antimony, arsenic, beryllium, cadmium, chromium, cobalt, lead, manganese, mercury, nickel and selenium) were matched to participants' residences of the same year. Adjusted logistic regression models were used to examine whether the airborne heavy metal associations differed by tumor ER/PR status. Principal component analysis was performed to assess associations by metal co-exposures. ResultsComparing the highest and lowest quintiles, higher concentrations of antimony (odds ratio[OR]: 1.8, 95% confidence interval[CI]: 0.9, 3.7, P-trend: 0.05), cadmium (OR: 2.3, 95% CI: 1.2, 4.4, P-trend: 0.04) and cobalt (OR: 2.0, 95% CI: 0.9, 4.4, P-trend: 0.04) were associated with ER/PR-negative breast cancer. Mixture analysis using principal components suggested co-exposures to multiple airborne heavy metals may drive associations with tumor receptor status. ConclusionsAmong women diagnosed with breast cancer, metallic air pollutants were associated with increased odds of developing ER/PR-negative breast cancer.

Leydig cell tumorigenesis - implication of G-protein coupled membrane estrogen receptor, peroxisome proliferator-activated receptor and xenoestrogen exposure. In vivo and in vitro appraisal

The etiology and molecular characteristics of Leydig cell tumor (LCT) are scarcely known. From the research data stems that estrogen can be implicated in LCT induction and development, however it is not investigated in detail. Considering the above, herein we analyzed the relation between G-protein coupled membrane estrogen receptor, peroxisome proliferator-activated receptor and insulin-like family peptides (insulin-like 3 peptide; INSL3 and relaxin; RLN) expressions as well as estrogen level with impact of xenoestrogen (bisphenol A; BPA, tetrabromobisphenol A; TBBPA, and tetrachlorobisphenol A; TCBPA). While in our previous studies altered GPER-PPAR partnership was found in human LCT being a possible cause and/or additionally effecting on LCT development, here mouse testes with experimentally induced LCT and mouse tumor Leydig cell (MA-10) treated with BPA chemicals were examined. We revealed either diverse changes in expression or co-expression of GPER and PPAR in mouse LCT as well as in MA-10 cells after BPA analogues when compared to human LCT. Relationships between expression of INSL3, RLN, including co-expression, and estrogen level in human LCT, mouse LCT and MA-10 cells xenoestrogen-treated were found. Moreover, involvement of PI3K-Akt-mTOR pathway or only mTOR in the interactions of examined receptors and hormones was showed.Taken together, species, cell of origin, experimental system used and type of used chemical differences may result in diverse molecular characteristics of LCT. Estrogen/xenoestrogen may play a role in tumor Leydig cell proliferation and biochemical nature but this issue requires further studies. Experimentally-induced LCT in mouse testis and MA-10 cells after BPA exposure seem to be additional models for understanding some aspects of human LCT biology.

Stomach-partitioning Gastrojejunostomy Versus Stent Placement for the Treatment of Malignant Gastric Outlet Obstruction

IntroductionGastric outlet obstruction is a complication of advanced tumors. It causes upper gastrointestinal obstruction, with progressive malnutrition and reduced survival. Currently, gastrojejunostomy or stent placement (SP) are feasible alternatives for the treatment of malignant gastric outlet obstruction. The aim of this study is to compare the efficacy and survival of both techniques. MethodsSingle-center observational and prospective study of 58 patients with gastric outlet obstruction who underwent surgical treatment with stomach-partitioning gastrojejunostomy (SPGJ) or SP with self-expanding intraluminal prostheses between 2007 and 2018. ResultsThirty patients underwent SPGJ and 28 SP. The mean age of the first group was significantly lower (69 vs. 78 years, respectively; P=.001). There were no statistically significant differences in terms of sex, perioperative risk or tumor etiology. Postoperative complications were non-significantly higher in the SPGJ group (P=.156). SP was associated with a shorter hospital stay (P=.02) and faster oral intake (P<.0001). However, SP had significantly higher rates of persistent and recurrent obstruction (P=.048 and 0.01, respectively), poorer energy targets (P=.009) and shorter survival (9.61 vs. 4.47 months; P=.008). ConclusionsSPGJ presents greater luminal permeability, better oral intake and greater survival than SP. SP is preferable for non-surgical patients with a limited short-term prognosis.

Long telomeres cooperate with p53, MDM2, and p21 polymorphisms to raise pediatric solid tumor risk.

While leukocyte telomere length has been linked with altered risk in adult cancer, limited information is available on its association with risk in pediatric solid tumors. We investigated the association of telomeric alterations with risk of pediatric solid tumors. We also investigated whether altered telomeres cooperated with the TP53 rs1042522, MDM2 rs2279744 and CDKN1A (p21cip1 ) rs1059234 single-nucleotide polymorphisms to modify cancer risk. A total of 101 tumor patients and 202 controls were recruited for this age- and gender-matched case-control study. Relative telomere length (RTL) was determined in peripheral blood leukocytes using quantitative real-time polymerase chain reaction (PCR), and the polymorphisms were genotyped using PCR-restriction fragment length polymorphism. Using median RTL in the healthy controls as a cut-off, children with longer telomeres were at an increased risk of developing a solid tumor (OR, 2.70; P<0.01). When participants were categorized according to control RTL quartiles, a significant dose-response relationship was observed (χ2 =10.95; P<0.001). The risk for tumors increased nearly threefold (P=0.001) for the triple interaction RTL × TP53 rs1042522×p21cip1 rs1059234 compared with the maximum effect of any single factor, although the interaction effect was less than additive. The MDM2 rs2279744 GG genotype reduced pediatric solid tumor risk significantly (OR, 0.51). Combined analysis of telomeres and genetic polymorphisms in the TP53 pathway can provide important clues to understanding pediatric solid tumor etiology.