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Endocrine Malignancies

Adrenocortical Cancer
Multiple Endocrine Neoplasia /Familial Thyroid Ca.
Pancreas Cancer
Parathyroid Cancer
Pheochromocytoma and Paraganglioma
Pituitary Cancer
Thymoma and Thymic Carcinoma
Thyroid Cancer
Medical Terminology for Cancer: The Endocrine System
Endocrinology / General Resources
Latest Research Publications

Endocrinology / General Resources (5 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Zhai T, Cui M, Chen G, et al.
Sclerosing Stromal Ovarian Tumor Combined with Early Onset Severe Preeclampsia. A Case Report.
J Reprod Med. 2015 May-Jun; 60(5-6):249-53 [PubMed] Related Publications
BACKGROUND: Sclerosing stromal tumor (SST) of the ovary is an extremely rare, benign, sex cord-stromal tumor. The tumor consists of cells with the multilineage potential of undifferentiated mesenchymal cells and the ability to secrete estrogen or androgen. Current research suggests that the tumor originates in the ovarian cortex. SSTs of the ovary are predominantly found in young women aged 20-30 years; information describing SST during pregnancy is limited.
CASE: We report a case of SST of the ovary combined with early onset severe preeclampsia.
CONCLUSION: We document the clinical and pathological characteristics of the patient's disease, including the effects on the pregnancy and fetus.

Melo SA, Luecke LB, Kahlert C, et al.
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
Nature. 2015; 523(7559):177-82 [PubMed] Related Publications
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1(+) crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1(+) crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1(+) crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.

Vučemilo L, Znaor T, Kuliš T, et al.
Thyroid cancer incidence and mortality trends in Croatia 1988-2010.
Acta Clin Croat. 2015; 54(1):30-7 [PubMed] Related Publications
The aim of our study was to describe and interpret national trends in thyroid cancer in Croatian men and women during the 1988-2010 period, to better understand the incidence and mortality trends in comparison with other populations, and to determine the proportion of certain histologic subtypes of thyroid cancer and their impact on these trends. Using information from the Croatian National Cancer Registry and WHO Mortality Database, we estimated trends in the age-standardized incidence and mortality rates by joinpoint regression analysis. Thyroid cancer incidence increased in both women and men during the study period, with the estimated annual percent change (EAPC) of 6.4% and 5.5%, with no joinpoints identified. A significant decrease in mortality (EAPC-2.1%) was observed in women, while in men mortality rates decreased nonsignificantly (EAPC-1.3%). A statistically significant incidence increase was observed only for papillary carcinomas with annual incidence increase by 6.7% for women and 7.9% for men. During the study period, thyroid cancer showed an incidence increase in Croatia with persistent and steady decrease in mortality in women and statistically nonsignificant decrease in mortality in men. The increase in papillary carcinomas led to the thyroid cancer incidence increase and also affected the thyroid cancer mortality decrease in women. The trends observed are similar to those in other European countries and require additional analysis to determine all factors that have an effect on them.

Halkia E, Spiliotis J
The role of cytoreductive surgery and HIPEC in epithelial ovarian cancer.
J BUON. 2015; 20 Suppl 1:S12-28 [PubMed] Related Publications
Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer in the Western world. The current standard treatment of these patients consists of cytoreduction and systemic chemotherapy. One of the most distinct features of EOC is the tendency to disseminate into the peritoneal cavity and remain confined to the peritoneum and intra-abdominal viscera. This makes it an ideal target for loco-regional therapy. Improved long-term results can be achieved in highly selected patients using cytoreductive surgery (CRS), in combination with intra-operative hyperthermic intra-peritoneal chemotherapy (HIPEC). Optimal cytoreduction of advanced ovarian cancer is currently the most relevant prognostic factor. However, even when a complete resection is possible, the appearance of recurrences during follow-up is very common, due to the presence of microscopic residual disease, not visible to the surgeon. HIPEC has become a useful therapeutic strategy to obtain a higher degree of debulking by trying to eliminate the residual microscopic component responsible for recurrences. A summary of the current clinical evidence suggests that the most interesting settings first to explore in randomized trials are secondary CRS after upfront incomplete CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure to initial standard therapy. There is much less indirect evidence for a potential benefit of HIPEC for less advanced stages (I - II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation). CRS and HIPEC offer a significant survival benefit in patients with recurrent EOC. This observation applies to both platinum-sensitive and platinum-resistant disease.

Vega-Vázquez MA, Gonzalez-Rodriguez L, Santiago-Rodríguez EJ, et al.
Quality of life-in patients with differentiated thyroid cancer at the general endocrinology clinics of the University Hospital of Puerto Rico.
Bol Asoc Med P R. 2015 Jan-Mar; 107(1):25-31 [PubMed] Related Publications
UNLABELLED: Differentiated thyroid cancer (DTC) can compromise the quality of life of patients. Our purpose is to investigate if the quality of life, in a cohort of patients in Puerto Rico, is affected by the diagnosis and/or treatment modalities received for DTC.
METHODS: This is a cross-sectional study of 75 subjects with DTC. A Spanish version of the University of Washington Quality of Life Questionnaire was used, including multiple aspects of physical and social functioning. Descriptive and bivariate analysis between domain scores and variables of interest were performed.
RESULTS: 82.7% of the patients reported that their health was the same or better than it was before treatment. The mean composite score obtained was 82.3, reflecting an overall little effect on quality of life. Patients diagnosed with DTC at an age of > or =45 years reported a significantly better score on the pain domain when compared with those diagnosed earlier (p < 0.05). Patient who received >150 mCi of radioiodine had a tendency towards a worse score on the same domain (p = 0.05).
CONCLUSIONS: Our cohort reported an overall minimal effect on the quality of life of patients with DTC. Future treatment strategies should include periodic quality of life evaluations, in order to tailor therapy in this growing population.

Patch AM, Christie EL, Etemadmoghadam D, et al.
Whole-genome characterization of chemoresistant ovarian cancer.
Nature. 2015; 521(7553):489-94 [PubMed] Related Publications
Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

Solmaz U, Mat E, Levent Dereli M, et al.
Does neoadjuvant chemotherapy plus cytoreductive surgery improve survival rates in patients with advanced epithelial ovarian cancer compared with cytoreductive surgery alone?
J BUON. 2015 Mar-Apr; 20(2):580-7 [PubMed] Related Publications
PURPOSE: To compare the outcomes of interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC/IDS) with primary debulking surgery (PDS) in patients diagnosed with advanced epithelial ovarian cancer (EOC).
METHODS: A total of 292 patients with stages IIIC and IV disease who were treated with either NAC/IDS or PDS between 1995 and 2012 were retrospectively reviewed. The study population was divided into two groups: the NAC/IDS group (N=84) and the PDS group (N=208). Progression-free survival (PFS), overall survival (OS), and optimal cytoreduction were compared.
RESULTS: The mean age was significantly higher in the NAC/IDS group (61.5±11.5 vs 57.8±11.1 years, p=0.01). Optimal cytoreduction was achieved in 34.5% (29/84) of the patients in the NAC/IDS group and in 32.2% (69/208) in the PDS group (p=0.825). The survival rates were comparable. The mean survival rate of patients who achieved optimal cytoreductive surgery in either the PDS or the NAC/IDS arm was significantly higher than that of patients who achieved suboptimal cytoreductive surgery (p<0.001 and p<0.001, respectively). Multivariate analysis confirmed the treatment method, amount of ascitic fluid, and optimal cytoreduction as independent factors for OS.
CONCLUSIONS: No definitive evidence was noticed regarding whether NAC/IDS increases survival compared with PDS. NAC should be reserved for patients who cannot tolerate PDS or when optimal cytoreduction is not feasible.

Koc M, Aktimur R, Kagan Gokakin A, et al.
Expression of FHIT, p16, p53 and EGFR as prognostic markers in thyroid tumors of uncertain malignant potential.
J BUON. 2015 Mar-Apr; 20(2):567-72 [PubMed] Related Publications
PURPOSE: Thyroid tumors of uncertain malignant potential (TT-UMP) constitute a relatively new diagnosis. The purpose of this study was to analyze the relationship between immunohistochemical panels, prognostic parameters and TT-UMP.
METHODS: Group I was composed of patients diagnosed as differentiated thyroid carcinoma (DTC) and Group II of patients diagnosed as TT-UMP. The prognostic scores of patients were calculated using data according to the well-known prognostic scoring systems MACIS, AMES, AGES. Evaluations of antibodies were based on the presence of nuclear staining for p16 and p53, membranous and cytoplasmic staining for epidermal growth factor receptor (EGFR) and cytoplasmic staining for fragile histidine triad (FHIT).
RESULTS: Statistically significant difference was noted (p< 0.05) between Group I and Group II according to MACIS and AMES. No statistical difference was found in terms of immunostaining between groups when stained with p16, p53 and FHIT. On the other hand, in Group II a moderate positive correlation was detected between MACIS and EGFR.
CONCLUSION: According to our findings p53 was not important in tumor genesis at early stages in well-differentiated thyroid carcinomas and p16 loss of expression could be used as a finding to help in difficult microscopic diagnosis. TT-UMP is a gray zone of lesions requiring specific therapeutic procedures and postoperative follow-up. A positive correlation was detected between EGFR and TT-UMP, leading to assume that this situation could be used as a new tool in the follow-up of these patients in the future.

Inic Z, Inic M, Jancic S, et al.
The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.
J BUON. 2015 Mar-Apr; 20(2):562-6 [PubMed] Related Publications
PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma.
METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed.
RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001).
CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Sun Y, Duan Q, Wang S, et al.
Diagnosis of pancreatic cancer using ¹⁸F-FDG PET/CT and CA19-9 with SUVmax association to clinical characteristics.
J BUON. 2015 Mar-Apr; 20(2):452-9 [PubMed] Related Publications
PURPOSE: To assess the ability of 18F-FDG PET/CT alone or combined with CA19-9 to diagnose pancreatic cancer and to analyze the correlation between maximal standardized uptake value (SUVmax) and clinical characteristics.
METHODS: Ninety-one patients diagnosed with pancreatic cancer using 18F-FDG PET/CT before treatment were analyzed. Definite diagnosis was by histology or cytology. The SUVmax of the primary tumor was used for the statistical analysis and, using the best cutoff value, the patients were divided into 2 groups: a high SUVmax group (SUV- max-5.49) and a low SUVmax group (SUVmax≤5.49). Logistic regression analysis and receiver operating characteristic (ROC) analysis were applied to analyze the effects of SUVmax and/or CA19-9 on the diagnosis of pancreatic cancer.
RESULTS: Of 91 patients, 80 had pancreatic cancer and 11 had benign conditions. The ROC curve analysis of the SUVmax yielded a best cutoff value of 5.49. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹⁸F-FDG PET/CT alone in the diagnosis of pancreatic cancer were 67.5, 72.73, 94.74, 23.53, and 68.13%, respectively, while these indices for ¹⁸F-FDG PET/CT combined with CA19-9 increased to 96.25, 63.64, 95.06, 70, and 92.31%, respectively. The area under the curve (AUC) of the SUVmax combined with CA19-9 was 0.94, which was significantly higher than that of the SUVmax or CA19-9 alone (p<0.05). The SUVmax value and CA19-9 levels in pancreatic cancer patients were significantly higher than those with benign conditions (p<0.05). Only the SUVmax in the pancreatic cancer patient group was associated with tumor size (p<0.05).
CONCLUSIONS: 18F-FDG PET/CT is a common examination for diagnosing pancreatic cancer, and the SUVmax combined with the CA19-9 level can significantly improve the sensitivity and accuracy in the diagnosis of pancreatic cancer. SUVmax is merely indicative of the volume of pancreatic cancer.

Kehoe S, Hook J, Nankivell M, et al.
Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.
Lancet. 2015; 386(9990):249-57 [PubMed] Related Publications
BACKGROUND: The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen.
METHODS: In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2), or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1.18. This trial is registered, number ISRCTN74802813, and is closed to new participants.
FINDINGS: Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22.6 months in the primary-surgery group versus 24.1 months in primary chemotherapy. The HR for death was 0.87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0.98 (95% CI 0.72-1.05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0.0007, and 14 women [6%] vs 1 woman [<1%], p=0.001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0.0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group.
INTERPRETATION: In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.
FUNDING: Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.

Khare V, Alam N, Saneja A, et al.
Targeted drug delivery systems for pancreatic cancer.
J Biomed Nanotechnol. 2014; 10(12):3462-82 [PubMed] Related Publications
Pancreatic cancer is usually diagnosed at the advanced stages, responds poorly to the available chemotherapeutics and constitutes the major factor for high mortality rate. Selective delivery of therapeutics to their cellular targets, without side effects is the foremost objective of the current investigations for effective treatment of pancreatic cancer. The development of the drugs which can selectively target pancreatic cancer along with carriers that can deliver drugs specifically to the rapidly dividing cells is considered as magic bullet for the efficient treatment of this fatal disease. This review describes various factors hampering the efficacy of drug targeting to pancreatic cancer including stromal fortress, hypocascularity, hyaluronan and interstitial fluid pressure, and exploration of various cellular targets for the site specific drug delivery. An account of burgeoning applications of novel drug delivery systems including nanoparticles, liposomes, quantum dots, micelles and drug conjugates in the management of pancreatic cancer is also provided. Additionally, potential of target based therapeutic agents and nanomedicines in clinical trials for the pancreatic cancer therapy are highlighted.

Ma FH, Qiang JW, Cai SQ, et al.
MR Spectroscopy for Differentiating Benign From Malignant Solid Adnexal Tumors.
AJR Am J Roentgenol. 2015; 204(6):W724-30 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to investigate the proton MR spectroscopy ((1)H-MRS) features of solid adnexal tumors and to evaluate the efficacy of (1)H-MRS for differentiating benign from malignant solid adnexal tumors.
MATERIALS AND METHODS: Sixty-nine patients with surgically and histologically proven solid adnexal tumors (27 benign and 42 malignant) underwent conventional MRI and (1)H-MRS. Single-voxel spectroscopy was performed using the point-resolved spectroscopy localization technique with a voxel size of 2 × 2 × 2 cm(3). Resonance peak integrals of choline, N-acetyl aspartate (NAA), creatine, lactate, and lipid were analyzed, and the choline-tocreatine, NAA-to-creatine, lactate-to-creatine, and lipid-to-creatine ratios were recorded and compared between benign and malignant tumors.
RESULTS: A choline peak was detected in all 69 cases (100%), NAA peak in 67 cases (97%, 25 benign and 42 malignant), lipid peak in 47 cases (17 benign and 30 malignant), and lactate peak in eight cases (four benign and four malignant). The mean (± SD) choline-tocreatine ratio was 5.13 ± 0.6 in benign tumors versus 8.90 ± 0.5 in malignant solid adnexal tumors, a statistically significant difference (p = 0.000). There were no statistically significant differences between benign and malignant tumors in the NAA-to-creatine and lipid-to-creatine ratios (p = 0.263 and 0.120, respectively). When the choline-to-creatine threshold was 7.46 for differentiating between benign and malignant tumors, the sensitivity, specificity, and accuracy were 94.1%, 97.1%, and 91.2%, respectively.
CONCLUSION: Our preliminary study shows that the (1)H-MRS patterns of benign and malignant solid adnexal tumors differ. The choline-to-creatine ratio can help clinicians differentiate benign from malignant tumors.

Wright JD, Chen L, Tergas AI, et al.
Trends in relative survival for ovarian cancer from 1975 to 2011.
Obstet Gynecol. 2015; 125(6):1345-52 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To examine relative survival (a metric that incorporates changes in survival within a population) in women with ovarian cancer from 1975 to 2011.
METHODS: Women diagnosed with ovarian cancer from 1975 to 2011 and recorded in the National Cancer Institute's Surveillance, Epidemiology, and End Results database were examined. Relative survival, estimated as the ratio of the observed survival of cancer patients (all-cause mortality) to the expected survival of a comparable group from the general population, was matched to the patients with the main factors that are considered to affect patient survival such as age, calendar time, and race. Hazard ratios were adjusted for age, race, year of diagnosis, time since diagnosis, and the interaction of age and years since diagnosis (except for stage II).
RESULTS: A total of 49,932 women were identified. For stage I ovarian cancer, the adjusted excess hazard ratio for death in 2006 was 0.51 (95% confidence interval [CI] 0.41-0.63) compared with those diagnosed in 1975. The reduction in excess mortality remained significant when compared with 1980 and 1985. For women with stage III-IV tumors, the excess hazard of mortality was lower in 2006 compared with all other years of study ranging from 0.49 (95% CI 0.44-0.55) compared with 1975 to 0.93 (95% CI 0.87-0.99) relative to 2000. For women aged 50-59 years, 10-year relative survival was 0.85 (99% CI 0.61-0.95) for stage I disease and 0.18 (99% CI 0.10-0.27) for stage III-IV tumors. For women aged 60-69 years, the corresponding 10-year relative survival estimates were 0.89 (99% CI 0.58-0.98) and 0.15 (99% CI 0.09-0.21).
CONCLUSION: Relative survival has improved for all stages of ovarian cancer from 1975 to 2011.

Chang YT, Tien YW, Jeng YM, et al.
Overweight increases the risk of malignancy in patients with pancreatic mucinous cystic neoplasms.
Medicine (Baltimore). 2015; 94(20):e797 [PubMed] Related Publications
Distinguishing between benign and malignant pancreatic cysts remains a clinical challenge. The aim of this study was to investigate the influence of body mass index (BMI) and preoperative clinical and cyst features, as described by the International Consensus Guidelines, on malignancy in patients with pancreatic mucinous cystic neoplasms (PMCNs).A retrospective cohort study was performed on patients with PMCNs who underwent surgical resection between January 1994 and June 2014. Preoperative BMI, clinical demographic data, cystic features, tumor markers, and surgical pathology results were analyzed. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression.One hundred sixty-four cases of PMCNs, including 106 intraductal papillary mucinous neoplasms (IPMNs) and 58 mucinous cystic neoplasms (MCNs), were analyzed. On univariate analysis, older age (P = 0.008), male sex (P = 0.007), high-risk stigmata (P = 0.007), diabetes mellitus (DM; P = 0.008), and BMI >25 (P < 0.001) were associated with malignancy. Multivariate analysis found that BMI >25 (odds ratio, 3.99; 95% confidence interval: 1.60-10) was an independent predictor of malignancy. In subgroup analysis, BMI >25 was an independent predictor of malignancy in IPMNs but not in MCNs.Overweight patients with IPMNs have a higher risk of malignancy and should be followed closely or undergo resection. The operative strategy for PMCNs should consider cyst-related and patient-related risk factors.

Liu G, Yang D, Rupaimoole R, et al.
Augmentation of response to chemotherapy by microRNA-506 through regulation of RAD51 in serous ovarian cancers.
J Natl Cancer Inst. 2015; 107(7) [PubMed] Related Publications
BACKGROUND: Chemoresistance is a major challenge in cancer treatment. miR-506 is a potent inhibitor of the epithelial-to-mesenchymal transition (EMT), which is also associated with chemoresistance. We characterized the role of miR-506 in chemotherapy response in high-grade serous ovarian cancers.
METHODS: We used Kaplan-Meier and log-rank methods to analyze the relationship between miR-506 and progression-free and overall survival in The Cancer Genome Atlas (TCGA) (n = 468) and Bagnoli (n = 130) datasets, in vitro experiments to study whether miR-506 is associated with homologous recombination, and response to chemotherapy agents. We used an orthotopic ovarian cancer mouse model (n = 10 per group) to test the effect of miR-506 on cisplatin and PARP inhibitor sensitivity. All statistical tests were two-sided.
RESULTS: MiR-506 was associated with better response to therapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (PFS: high vs low miR-506 expression; Bagnoli: hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.90 to 4.70, P < .0001; TCGA: HR = 1.49, 95% CI = 1.00 to 2.25, P = 0.04). MiR-506 sensitized cells to DNA damage through directly targeting the double-strand DNA damage repair gene RAD51. Systemic delivery of miR-506 in 8-12 week old female athymic nude mice statistically significantly augmented the cisplatin and olaparib response (mean tumor weight ± SD, control miRNA plus cisplatin vs miR-506 plus cisplatin: 0.36±0.05g vs 0.07±0.02g, P < .001; control miRNA plus olaparib vs miR-506 plus olaparib: 0.32±0.13g vs 0.05±0.02g, P = .045, respectively), thus recapitulating the clinical observation.
CONCLUSIONS: MiR-506 is a robust clinical marker for chemotherapy response and survival in serous ovarian cancers and has important therapeutic value in sensitizing cancer cells to chemotherapy.

de Mestier L, Hentic O, Cros J, et al.
Metachronous hormonal syndromes in patients with pancreatic neuroendocrine tumors: a case-series study.
Ann Intern Med. 2015; 162(10):682-9 [PubMed] Related Publications
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described.
OBJECTIVE: To describe MHSs in patients with sporadic PNETs.
DESIGN: Retrospective, multicenter study.
SETTING: 4 French referral centers.
PATIENTS: Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014.
MEASUREMENTS: Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling.
RESULTS: Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs.
LIMITATION: Retrospective data collection and heterogeneity of pathologic specimen size and origin.
CONCLUSION: Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates.

Li HM, Qiang JW, Xia GL, et al.
Primary ovarian endometrioid adenocarcinoma: magnetic resonance imaging findings including a preliminary observation on diffusion-weighted imaging.
J Comput Assist Tomogr. 2015 May-Jun; 39(3):401-5 [PubMed] Related Publications
OBJECTIVE: This study aimed to investigate the magnetic resonance imaging (MRI) features of ovarian endometrioid adenocarcinoma (OEC) and to evaluate conventional MRI and diffusion-weighted imaging (DWI) for diagnosing OEC.
MATERIALS AND METHODS: Twenty patients with OEC proven by surgery and pathology underwent MRI. The MRI features of the tumors evaluated included laterality, shape, size, configuration, mural nodules, signal intensity, apparent diffusion coefficient (ADC) values, enhancement, peritoneal implants, ascites, and synchronous primary cancer (SPC) of the ovary and endometrium.
RESULTS: Unilateral ovarian masses were observed in 18 (90%) of the 20 patients with 22 OEC lesions, whereas the remaining 2 (10%) patients had bilateral masses. Oval, lobulated, and irregular shapes were observed in 13 (59%), 6 (27%), and 3 (14%) tumors, respectively. The maximum diameter of the tumors ranged from 3.7 to 22.5 cm, with a mean of 11.2 ± 5.1 cm. Fifteen (68%) masses were mainly cystic with mural nodules, 5 (23%) were mixed cystic-solid, and 2 (9%) were solid. The solid components of tumors showed isointensity (100%) on T1-weighted imaging (T1WI), heterogeneous hyperintensity on T2-weighted imaging (T2WI) (86%), and hyperintensity on DWI (82%), with a mean ADC value of (0.96 ± 0.20) × 10 mm/s. The cystic components showed isointensity or hyperintensity (85%) on T1WI, hyperintensity on T2WI (100%), and hypointensity on DWI (63%), with a mean ADC value of (2.27 ± 0.27) × 10 mm/s. Ten (50%) of the patients were SPC. The mean ADC values of the solid components were (0.85 ± 0.19) × 10 mm/s and (1.08 ± 0.15) × 10 mm/s in only-OEC and SPC, respectively, with a statistically significant difference (P = 0.012).
CONCLUSIONS: Ovarian endometrioid adenocarcinoma usually appears as a large, oval, or lobulated cystic mass with mural nodules. Cystic components show isointensity or hyperintensity on T1WI, solid components and hyperintensity on T2WI and DWI. Synchronous primary cancer of the ovary endometrium is another characteristic feature of OEC.

Lien RJ, Corcuera-Solano I, Pawha PS, et al.
Three-Tesla imaging of the pituitary and parasellar region: T1-weighted 3-dimensional fast spin echo cube outperforms conventional 2-dimensional magnetic resonance imaging.
J Comput Assist Tomogr. 2015 May-Jun; 39(3):329-33 [PubMed] Related Publications
OBJECTIVE: We explored how a novel T1-weighted 3-dimensional (3D) fast spin echo (FSE) sequence (Cube; GE, Waukesha, Wis) might outperform conventional 2-dimensional (2D) FSE techniques for contrast-enhanced imaging of the pituitary and parasellar region.
METHODS: Ninety-one patients were imaged with 3D Cube and conventional 2D FSE on a 3.0-T magnetic resonance scanner. Two neuroradiologists independently assessed images for anatomical delineation (infundibulum, optic apparatus, and cavernous sinus), degree of artifact, and confidence in lesion definition or exclusion using a 5-point scale. In addition, the readers were asked to rank overall preference.
RESULTS: Readers A and B found 3D Cube to be better or equal to 2D FSE in 84% and 86% of the cases. Three-dimensional Cube provided significantly better images than 2D FSE with respect to delineation of the infundibulum (P < 0.0001), cavernous sinus (P < 0.0001), optic apparatus (P = 0.002 for reader A and P = 0.265 for reader B), and fewer artifacts at the sellar floor (P < 0.0001). Three-dimensional Cube provided greater lesion conspicuity or confidence in lesion exclusion (P < 0.0001).
CONCLUSIONS: Three-dimensional Cube provides superior quality with thinner slices as well as diminished artifact and can replace conventional 2D FSE sequences for routine evaluations of the pituitary and parasellar region.

Ito T, Hamasaki M, Matsumoto S, et al.
p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer.
Am J Clin Pathol. 2015; 143(6):830-8 [PubMed] Related Publications
OBJECTIVES: It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC.
METHODS: p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion.
RESULTS: According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%.
CONCLUSIONS: Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.

Chernock RD, Hagemann IS
Molecular pathology of hereditary and sporadic medullary thyroid carcinomas.
Am J Clin Pathol. 2015; 143(6):768-77 [PubMed] Related Publications
OBJECTIVES: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease.
METHODS: A review of published literature was performed.
RESULTS: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors.
CONCLUSIONS: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.

Buzdugă CM, Găleşanu C, Vulpoi C, et al.
Thyroid fine-needle biopsy: aspiration versus capillary.
Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar; 119(1):45-50 [PubMed] Related Publications
UNLABELLED: Thyroid nodules are a common pathology of the thyroid gland. Thyroid fine-needle biopsy (FNB) is a technique used as the first step in the assessment of thyroid nodules. Some au- thors have demonstrated the superiority of nonaspiration compared with aspiration biopsy.
AIM: The objective was to assess whether there are significant differences between the two thyroid biopsy techniques.
MATERIAL AND METHODS: The study group comprised 309 patients with thyroid nodules admitted to the Endocrinology Clinic of the Iasi "St. Spiridon "Hospital between 2005 and 2008 in which fine-needle nonaspiration or aspiration biopsy was performed. The slides were read by one pathologist. The smears were stained using the May-Grunwald-Giemsa method (MGG). The quality of smears obtained by the two sampling techniques was evaluated by using the scoring system developed by Mair.
RESULTS AND DISCUSSION: No differences in smear quality between the two sampling techniques in terms of blood contamination, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and preservation of appropriate architecture were found.
CONCLUSION: The results of this study show that the sensitivity and specificity of both techniques allow their use as standard screening methods for thyroid nodular lesions.

Ilić MB, Jovanović DV, Milosavljević MZ, et al.
Hypercalcemic type of small cell carcinoma of the ovary.
Vojnosanit Pregl. 2015; 72(3):295-8 [PubMed] Related Publications
INTRODUCTION: Extrapulmonary small cell carcinoma is a rare, prognostically bad tumor category. Primary, it can be localized in every organ, even in the ovary, where, due to its clinical specificities, it represents a challenge in diagnosis, as well as in therapy. Small cell ovarian carcinoma (SCOC) is biologically very aggressive malignant tumor of unknown histogenesis. We presented a rare case of SCOC with hypercalcemia of aggressive course and fatal outcome in a postmenopausal woman at International Federation of Gynecology and Obstetrics (FIGO) Ia stage.
CASE REPORT: A 60-year-old woman, Caucasian, came to the doctor because of discomfort in the lower abdomen and pain of greater intensity in last few days. Ultrasound examination and CT scan of the abdomen confirmed the presence of large adnexal masses of cystic-solid appearance with the largest diameter of 13 cm, regular structure of the other gynecological organs, without verifying the existence of metastatic deposits. All the results of laboratory analysis gave normal values, except for calcium, which was elevated. Explorative laparotomy with complete hysterectomy, bilateral salpingo-oophorectomy, dissection of lymph nodes and omentectomy were conducted. Based on pathohistological analysis of the operative material, SCOC at FIGO Ia stage was diag- nosed. No complications were observed in a postsurgery period and after 10 days the patient was discharged in a good condition and with normal calcemia. The treatment was continued with concurrent radiotherapy and chemotherapy. However, in spite of overall treatment, the disease progressed, and the patient died of disseminated metastatic disease, 26 months after the diagnosis.
CONCLUSION: Small cell carcinoma localized in the ovary is generally a tumor category with bad prognosis depending on the stage of the disease.

Salehi M, Nalaini F, Izadi B, et al.
Gray-scale vs. color doppler ultrasound in cold thyroid nodules.
Glob J Health Sci. 2015; 7(3):147-52 [PubMed] Related Publications
We intended to compare gray-scale vs. color Doppler ultrasound findings in cold thyroid nodules. Sixty-four patients with cold thyroid nodules for whom the presumptive diagnosis of malignancy (based on isotope scan study) had been made were consecutively included. They underwent gray-scale and color Doppler sonography studies. Based on histopathologic examination of surgically removed nodules, there were respectively 25 (39%) and 39 (61%) malignant and benign nodules. On color Doppler sonography, preference central hypervascularity was the most common finding in malignant nodules (17 nodules, 68%). Among benign nodules, preference perinodular hypervascularity was the most common finding (26 nodules, 66.7%). The most sensitive and specific Doppler sonography findings for malignant nodules were preference central hypervascularity (68%) and only central vascularity (97%), respectively. On gray-scale sonography, absent halo sign was the most common finding in malignant nodules (20 nodules, 80%). Among benign nodules, microcalcification was the most common finding which was reported in 12 nodules (30.7%). Hypoechogenicity was the most specific finding (76.9%) for malignant nodules. Since both gray-scale and color Doppler ultrasonography are inexpensive, non-invasive, and accessible methods to diagnose thyroid malignant cold nodules, it is recommended that these methods be applied by clinicians to assist or even substitute other invasive methods.

Doron O, Carmon E
An incidental suprasellar mass in a military flying cadet: implications for aircrew.
Aerosp Med Hum Perform. 2015; 86(5):477-80 [PubMed] Related Publications
BACKGROUND: Incidental findings pose a dilemma in aviation medicine, where every finding must be carefully considered in order to ensure the well-being of the aircrew for flight and mission safety. Since suprasellar masses are not uncommon, their possible effects should be addressed.
CASE REPORT: We present an incidental finding of 11.5 mm × 14.4 mm, hyper-intense on T2 and iso-intense on T1-weighted images, of a suprasellar mass in a 19-yr-old man. This finding led to the re-evaluation of his position as a military flight cadet, followed by his later disqualification.
DISCUSSION: No medical waiver regarding asymptomatic suprasellar mass exists. We have carefully examined the differential diagnosis and generated a profile for each possible diagnosis consisting of risks for sudden incapacitation, progression likelihood, and the effect of an aerial environment on a brain lesion. We were able to draw up a medical waiver for some of the possible diagnoses (namely, Rathke's cyst or craniopharyngioma) for nonhigh performance aircraft.

Moore JL, Jackson CR, Ellis JC, Norrid C
You're the flight surgeon: myelolipoma.
Aerosp Med Hum Perform. 2015; 86(4):421-3 [PubMed] Related Publications
Moore JL, Jackson CR, Ellis JC, Norrid C. You're the flight surgeon: myelolipoma. Aerosp Med Hum Perform. 2015; 86(4):421-423.

Luo S, Wang J, Ma Y, et al.
PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b.
Biochem Biophys Res Commun. 2015; 462(2):85-90 [PubMed] Related Publications
miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer.

Hiraoka N, Ino Y, Yamazaki-Itoh R, et al.
Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer.
Br J Cancer. 2015; 112(11):1782-90 [PubMed] Related Publications
BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs.
METHODS: We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics.
RESULTS: There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes.
CONCLUSIONS: Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained.

Rizzo S, Origgi D, Brambilla S, et al.
Radiation exposure of ovarian cancer patients: contribution of CT examinations performed on different MDCT (16 and 64 slices) scanners and image quality evaluation: an observational study.
Medicine (Baltimore). 2015; 94(17):e765 [PubMed] Related Publications
The objective of this study is to compare radiation doses given to ovarian cancer patients by different computed tomographies (CTs) and to evaluate association between doses and subjective and objective image quality.CT examinations included were performed either on a 16-slice CT, equipped with automatic z-axis tube current modulation, or on a 64-slice CT, equipped with z-axis, xy-axis modulation, and adaptive statistical iterative algorithm (ASIR). Evaluation of dose included the following dose descriptors: volumetric CT dose index (CTDIvol), dose length product (DLP), and effective dose (E). Objective image noise was evaluated in abdominal aorta and liver. Subjective image quality was evaluated by assessment of image noise, spatial resolution and diagnostic acceptability.Mean and median CTDIvol, DLP, and E; correlation between CTDIvol and DLP and patients' weight; comparison of objective noise for the 2 scanners; association between dose descriptors and subjective image quality.The 64-slice CT delivered to patients 24.5% lower dose (P < 0.0001) than 16-slice CT. There was a significant correlation between all dose descriptors (CTDIvol, DLP, E) and weight (P < 0.0001). Objective noise was comparable for the 2 CT scanners. There was a significant correlation between dose descriptors and image noise for the 64-slice CT, and between dose descriptors and spatial resolution for the 16-slice CT.Current dose reduction systems may reduce radiation dose without significantly affecting image quality and diagnostic acceptability of CT exams.

Xia D
Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro.
Nat Prod Commun. 2015; 10(2):249-52 [PubMed] Related Publications
The effect and mechanism of ovarian cancer HO-8910 cell apoptosis induced by crocin.MTT assay was performed to detect the inhibitory action of crocin on the proliferation of HO-8910 cells. Flow cytometry was used to test the cell cycle distribution and apoptosis rate of ovarian cancer HO-8910 cells. Western blot analysis was utilized to measure the levels of apoptotic proteins such as p53, Fas/APO-1, and Caspase-3. MTT analysis revealed that crocin significantly inhibited the growth of HO-8910 cells. Additionally, flow cytometry illustrated that crocin raised the proportion of HO-8910 cells in the G0/G1 phase and increased their apoptosis rate. Furthermore, Western blot analysis revealed that crocin up-regulated the expression of p53, Fas/APO-1, and Caspase-3. The results of this study showed that crocin can significantly inhibit the growth of HO-8910 cells and arrest them in the G0/G1 phase. Crocin can also promote ovarian cancer HO-8910 cell apoptosis, most likely by increasing p53 and Fas/APO-1 expression, and then activating the apoptotic pathway regulated by Caspase-3.

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