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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).

Fox RG, Lytle NK, Jaquish DV, et al.
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.
Nature. 2016; 534(7607):407-11 [PubMed] Related Publications
Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression both in genetic models and in patient-derived xenografts. Specifically, we developed Msi reporter mice that allowed image-based tracking of stem cell signals within cancers, revealing that Msi expression rises as pancreatic intraepithelial neoplasia progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreatic cancer: they preferentially harbour the capacity to propagate adenocarcinoma, are enriched in circulating tumour cells, and are markedly drug resistant. This population could be effectively targeted by deletion of either Msi1 or Msi2, which led to a striking defect in the progression of pancreatic intraepithelial neoplasia to adenocarcinoma and an improvement in overall survival. Msi inhibition also blocked the growth of primary patient-derived tumours, suggesting that this signal is required for human disease. To define the translational potential of this work we developed antisense oligonucleotides against Msi; these showed reliable tumour penetration, uptake and target inhibition, and effectively blocked pancreatic cancer growth. Collectively, these studies highlight Msi reporters as a unique tool to identify therapy resistance, and define Msi signalling as a central regulator of pancreatic cancer.

Preechasuk L, Pongpaibul A, Kunavisarut T
Non-insulinoma Pancreatogeneous Hypoglycemia Syndrome with False-Positive Somatostatin Receptor Scintigraphy: A Case Report and Review of Literature.
J Med Assoc Thai. 2016; 99(3):354-9 [PubMed] Related Publications
Non-insulinoma pancreatogeneous hypoglycemia syndrome (NIPHS) is a rare cause of hypoglycemia in adults. The cause of NIPHS is diffuse hyperinsulinism. As a result, computed tomography (CT) of pancreas, endoscopic pancreatic ultrasonography (EUS), and somatostatin receptor scintigraphy (SSRS), which are usually performed to locate an insulinoma, are not able to diagnose NIPHS. Moreover, SSRS can give a false-positive result. In this case report, we introduce a 22-year-old Thai woman who presented with fasting and postprandial hyperinsulinemic hypoglycemia. Accordingly, an insulinoma was suspected. She underwent several studies to locate the lesion. Pancreatic CT and EUS failed to locate a lesion; however, SSRS showed a faint focus of increased uptake at the pancreatic head. The suspected insulinoma was not identified during a first operation. Thereafter other diagnostic methods were performed in an effort to locate the suspected insulinoma, including selective arterial calcium stimulation test. The result of the selective arterial calcium stimulation test was negative. Intraoperative ultrasonography during a second operation also failed to locate a tumor. Finally, a pancreatic head resection was performed according to SSRS result, yet capillary blood glucose levels did not increase after resection. In response, a 95% pancreatectomy was performed. The pathology report was consistent with diffuse hyperinsulinism. This report emphasizes that SSRS can give false positive result in NIPHS.

Tsiambas E, Ragos V, Georgakopoulos G, et al.
E-cadherin/α-catenin deregulated co-expression in thyroid carcinoma based on tissue microarray digital image analysis.
J BUON. 2016 Mar-Apr; 21(2):450-5 [PubMed] Related Publications
PURPOSE: Deregulation of cell-to-cell adhesion molecules is a common and also critical genetic event in epithelial malignancies leading to an increasing metastatic potential. Among them, e-cadherin and catenins--especially α and β--, act as oncogenes during the carcinogenetic process affecting specific signaling transduction pathways (i.e. Wnt/ b-catenin). Concerning thyroid carcinoma, decreased or loss of expression in these proteins seems to affect the biological behavior of the neoplasm increasing its aggressiveness. The aim of this study was to investigate the deregulation of e-cadherin/α-catenin complex in thyroid carcinomas.
METHODS: Thirty-five paraffin-embedded tissue samples including thyroid carcinomas (N=20) and also 15 cases of benign follicular nodules were cored at 1 mm diameter and transferred to a microarray block. Immunohistochemistry (IHC) was performed using anti-e-cadherin/α-catenin antibodies. Digital image analysis was also implemented for measuring the corresponding protein expression levels.
RESULTS: E-cadherin/α-catenin protein expression demonstrated a significant progressive decrease regarding benign and malignant lesions (p=0.001). Simultaneous e-cadherin/α-catenin reduced or loss of expression was observed in 10/20 (50%) cancer cases correlated to advanced stage (especially nodal metastasis) of the examined tumours (p=0.02). Concerning the histological type, combined loss of e-cadherin/α-catenin expression was predominantly associated with follicular and anaplastic histology (p=0.001). Interestingly, α-catenin protein expression pattern was significantly correlated with the grade of differentiation of the examined malignancies (p=0.01).
CONCLUSIONS: Progressive loss of e-cadherin mainly and also α-catenin expression is associated with an aggressive phenotype (low differentiation, increased metastatic activity/advanced stage) in thyroid carcinomas. Based on their aberrant protein expression, novel agents have been developed for restoring their normal function.

Kilic Sakarya D, Yetimalar MH
Is there a current change of maintenance treatment in ovarian cancer? An updated review of the literature.
J BUON. 2016 Mar-Apr; 21(2):290-300 [PubMed] Related Publications
Maintenance therapy in ovarian cancer has been introduced and evaluated in many large randomized trials; however, its efficacy is still unclear and includes concerns for both short-term and longer-term side effects. Thus far, some therapies that have been studied in this setting showed a delay in tumor progression but unfortunately no improvement in overall survival has been noticed. The introduction of new chemotherapeutic agents redirected research efforts. Assessing benefits of prolonged therapy and its impact in terms of toxicity is considerably important for the decision to administer such treatments. The purpose of this article was to provide an update on the randomized trials and review the role of maintenance therapy in the treatment of ovarian cancer.

Wierzbicka-Tutka I, Sokołowski G, Bałdys-Waligórska A, et al.
PTTG and Ki-67 expression in pituitary adenomas.
Przegl Lek. 2016; 73(2):53-8 [PubMed] Related Publications
INTRODUCTION: The unpredictable biology of pituitary adenomas makes it a therapeutic challenge. Moreover ,histopathology of pituitary carcinomas and locally invasive adenomas are indistinguishable from benign tumors and a new marker which would enable to differentiate those lesions is vital. The aim of the study was to evaluate Ki-67 and PTTG (pituitary tumour--transforming gene) expression in pituitary adenomas and their applicationas markers of tumour aggressiveness.
MATERIAL AND METHODS: A retrospective analysis of 55 patients: 32 females(58%) and 23 males (42%), mean age 50 ± 16 years who underwent pituitary tumor surgery between 2003-2012. Ki-67 and PTTG indices were determined by immunohistochemical staining. Magnetic resonance imaging or computed tomography was performed beforehand and one year after surgery to figure a potential tumour progression, tumour size and correlation to adjacent tissues.
RESULTS: The expression of Ki-67and PTTG was revealed in cell nucleiin 88% and 85% of adenomas, respectively. The median Ki-67 and PTTG indices were 1.4 and 1.0, respectively(p = 0.006). In the group with macroadenoma as compared with the group with microadenoma, median Ki-67 index was higher (1.4% vs. 1.03%; p = 0.02). We did not find correlation between both Ki-67 and PTTG indices and tumour progression. Tumours with positive immunostaining towards FSH revealed lower Ki-67 and PTTG indices than the rest with a negative one (0.6% vs.1.84%, p = 0.0004 and 0.67% vs 1.23%,p = 0.047; respectively). However, PTTG index was higher in the group with acromegaly as compared to the group with clinically non-functioning pituitary adenoma (NFPA) (1.28% vs.0.35%; p = 0.02).
CONCLUSIONS: Positive nuclear expression of Ki-67 and PTTG was observed in the majority of pituitary adenomas. Only higher Ki-67 expression was related to the tumour invasiveness found on MRI/CT. Tumour progressionwas not related to both Ki-67 and PTTG expression.

Stark A, Donahue TR, Reber HA, Hines OJ
Pancreatic Cyst Disease: A Review.
JAMA. 2016; 315(17):1882-93 [PubMed] Related Publications
IMPORTANCE: Cystic lesions of the pancreas are common and increasingly detected in the primary care setting. Some patients have a low risk for developing a malignancy and others have a high risk and need further testing and interventions.
OBSERVATIONS: Pancreatic cysts may be intraductal mucinous neoplasms, mucinous cystic neoplasms, serous cystadenomas, solid pseudopapillary neoplasms, cystic variations of pancreatic neuroendocrine tumors, pancreatic ductal adenocarcinomas, or 1 of several types of nonneoplastic cysts. Mucinous (intraductal mucinous neoplasm or mucinous cystic neoplasm) lesions have malignant potential and should be distinguished from serous lesions (serous cystadenomas) that are nearly always benign. Symptomatic patients or those having high-risk features on initial imaging (eg, main pancreatic duct dilatation, a solid component, or mural nodule) require further evaluation with advanced imaging, possibly followed by surgical resection. Advanced imaging includes endoscopic ultrasound with cyst fluid analysis and cytology to confirm the type of cyst and determine the risk of malignancy. Small cysts (size <3 cm) in asymptomatic patients without any suspicious features may be observed with serial imaging because the risk for malignancy is low.
CONCLUSIONS AND RELEVANCE: The management of pancreatic cysts requires risk stratification for malignant potential based on the presence or absence of symptoms and high-risk features on cross-sectional imaging. Because pancreatic cysts are becoming more frequently diagnosed, clinicians should have a systematic approach for establishing a diagnosis and determining which patients require treatment.

Hammel P, Huguet F, van Laethem JL, et al.
Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial.
JAMA. 2016; 315(17):1844-53 [PubMed] Related Publications
IMPORTANCE: In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown.
OBJECTIVES: To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival.
DESIGN, SETTING, AND PARTICIPANTS: In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013.
INTERVENTIONS: In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine).
MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects.
RESULTS: A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea.
CONCLUSIONS AND RELEVANCE: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00634725.

Mirjalili SM, Hashemipour S, Salehi S, et al.
Thyroid metastasis of bladder transitional cell carcinoma.
Malays J Pathol. 2016; 38(1):65-70 [PubMed] Related Publications
The thyroid gland is a rare site for cancer metastasis. We report a 75-year-old man who was referred with a history of hematuria and generalized bone pain for the past few months. He had a past history of partial left lobe thyroidectomy for follicular adenoma. Subsequently he was referred for a thyroid mass and a subtotal thyroidectomy showed a poorly-differentiated carcinoma. On the latest admission, the patient underwent resection of a bladder tumour with malignant histology and an immunohistochemical profile of CK7+/CK20+/34 Beta E12+/CEA-/PSA-. Re-examination of thyroid sections with immunohistochemical stains revealed the malignant cells to be CK7+/CK20+/34 Beta E12+/CEA-/TTF1-. The findings were compatible with metastasis of the bladder transitional cell carcinoma to the thyroid gland.Scans revealed multiple liver and bone metastases. The patient died 2 months after the diagnosis.

Manea E, Munteanu A
Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar; 120(1):192-6 [PubMed] Related Publications
Bilateral breast cancer incidence is appreciated to be between 0.3 to 12% and is determined either by a hereditary load associated with chromosomal instability under the effect of environmental factors, or by the evolution in a particular hormonal context which gives biological aggressiveness. We present the case of a patient, aged 38 years, clinically, imagistic and bioptic diagnosed with left axillary lymph node metastases of breast carcinoma NST invasive G3, IHC-RE = 60%, RP = 30%, HER2neu = 2 +, Ki67 = 20%, in August 2013. Patient followed neoadjuvant chemotherapy treatment during September-October 2013. In December 2013 she was clinically and imaging diagnosed with bilateral breast cancer, for which surgical intervention was done which consisted of bilateral radical Madden mastectomy with bilateral axillary lymphadenectomy. BAP-invasive carcinoma NST: left breast-pT2mN3a G2, right breast--pT3mN3a G2, IHC-RE = 90%, RP =70% HER2neu = 2 +, Ki67 = 50%. During the period of January-March 2014, the patient followed adjuvant chemotherapy and Herceptin. Bilateral breast ultrasound assessment in April 2014 revealed: left axilla--liquid blade 29 / 6mm; right axilla--oval ganglion 9/5 mm. Abdominal and pelvic ultrasound: empty uterine cavity, bosselated contour; at left ovary level multiple cystic formations. During the period of May-June 2014, adjuvant radiation therapy and ovarian irradiationwas administered to the patient. Subsequently hormone therapy was initiated. Following CHT / ovarian irradiation patient continues to experience intermittent uterine bleeding, which is why a total hysterectomy with bilateral ovariectomy was done, and BAP: cervical, endometrialand left ovary with tumor multifocal infiltration with histopathological aspect of invasive breast carcinoma NST. Periodic imaging evaluations do not reveal local or distant recurrence. The particularity of this case is synchronous bilateral breast cancer diagnosis in a young patient complicated in its evolution by ovarian metastases. This form of metastasis is rare in young women and occurs in advanced stages of the disease.

Jovanović M, Janjusević N, Mirković D, et al.
Giant primary retroperitoneal seminoma: A case report.
Vojnosanit Pregl. 2016; 73(2):205-7 [PubMed] Related Publications
INTRODUCTION: Primary extragonadal seminomas are rare tumors. There have been only a few cases of the primary retroperitoneal seminomas reported in the literature up to date.
CASE REPORT: We reported a 56-year-old man with giant primary retroperitoneal seminoma presented with the enlargement of the left side of the abdomen and deep venous thrombosis of the left leg. Computed tomography of the abdomen showed a large tumor occupying the left part of the retroperitoneal space with 23 x 13 cm in diameter. Firm tumor mass having 25 x 15 cm in diameter was surgically removed from the left retroperitoneum. The tumor adhered the tunica adventitia of the aorta and it was carefully resected from the aortic wall. The diagnosis of seminoma was made during histopathological examination. The patient underwent chemotherapy. Two years after finished chemotherapy the patient accepted left orchiectomy with the aim of eliminating the possibility of the occult malignancy of the testicle. Histopathological analysis of the testicular tissue was normal and the diagnosis of primary retroperitoneal seminoma was confirmed. CONCLUSION. Despite its small incidence in general population, the diagnosis of retroperitoneal seminoma should be considered in male patients with nonspecific symptoms and with retroperitoneal tumor mass.

Zhai DK, Liu B, Bai XF, Wen JA
Identification of biomarkers and pathway-related modules involved in ovarian cancer based on topological centralities.
J BUON. 2016 Jan-Feb; 21(1):208-20 [PubMed] Related Publications
PURPOSE: The present study was designed to explore the significant biomarkers and pathway-related modules for predicting the effects of eribulin relative to paclitaxel in ovarian cancer.
METHODS: The gene expression data E-GEOD-50831 were downloaded from the European Bioinformatics Institute (EBI) database. Differentially expressed genes (DEGs) were screened. Subsequently, differential coexpression network was constructed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway-related modules mining were conducted. Topological centralities (degree, betweenness, closeness and stress) analyses for coexpression network and pathway-related modules were performed to explore hub genes and the most significant pathways. Then, we verified our findings in an independent sample set via RT-PCR and Western blotting.
RESULTS: Centralities results of ESCO1, CDC27and MCM4 ranked the top five. Moreover, among the top 10% hub genes, CDC27, MCM4 and SOS1 were pathway-enriched genes in two networks. A total of 5 and 6 pathway-related modules were obtained under two drugs treatment. Based analyses of degree, betweenness and other centralities, DNA replication pathway-related module was the most significant under paclitaxel treatment, while cell cycle pathway-related module was the most significant under eribulin treatment. RT-PCR and Western blotting results were consistent with the bioinformatics results. The expression level of MCM4 was remarkably decreased under eribulin treatment relative to paclitaxel.
CONCLUSIONS: The inhibition of ovarian cancer growth by paclitaxel and eribulin might be connected with downregulation of cell cycle and DNA replication pathway. Moreover, MCM4 signature might be a potential biomarker to predict the effect of eribulin in ovarian cancer.

Seifert L, Werba G, Tiwari S, et al.
The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.
Nature. 2016; 532(7598):245-9 [PubMed] Article available free on PMC after 06/10/2016 Related Publications
Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Zhou LY, Shi LY, Xiao Y
Changes of HMGB1 expression on angiogenesis of ovarian cancer and its mechanism.
J Biol Regul Homeost Agents. 2016 Jan-Mar; 30(1):233-8 [PubMed] Related Publications
This study was designed to investigate the changes of high-mobility group box-1 (HMGB1) expression and its effects on regulating the angiogenesis of ovarian cancer. HMGB1 eukaryotic expression plasmid and artificially synthesized small interfering ribose nucleic acid (siRNA) were constructed to transfer SKOV3 cell, respectively. Western blot was adopted to investigate the changes of HMGB1, CXCL12 and vascular endothelial growth factor (VEGF) before and after the transfection and flow cytometry (FCM) was applied to detect SKOV3 apoptosis. Results revealed that the apoptosis rates of SKOV3 cell were 32.8±2.2%, 33.9±1.9% and 11.7±1%, respectively, in the control group, no-load group and transfection group after 2-d cisplatin treatment (10 μg/mL). The apoptosis rate in the transfection group was obviously lower than that in the control group and no-load group (p = 0.00) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.75). Furthermore, the apoptosis rates of SKOV3 cell in the SKOV3 group, negative control group, SKOV3-ribose nucleic acid interfere (RNAi) group were 7.9±0.5%, 8.3±0.8% and 29.5±1.3% respectively. The apoptosis rate was notably higher in SKOV3-RNAi group than in the SKOV3 group and negative control group (p < 0.001) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.89). Thus, it can be concluded that HMGB1 interference can reduce VEGF and CXCL12 expression in ovarian cancer cells, but increase the apoptosis of ovarian cancer cells. Moreover, HMGB1 is highly expressed in cytoplasm and karyon.

Moszynski R, Szubert S, Tomczak D, et al.
Solitary fibrous mass of the omentum mimicking an ovarian tumor: case report.
Eur J Gynaecol Oncol. 2016; 37(1):144-7 [PubMed] Related Publications
There are some pelvic masses which are difficult to correctly classify as malignant or benign. The decision concerning method and choice of surgical intervention is not simple in this situation. Some tumors are extremely rare and need to be presented in the literature. The authors report a rare case of fibrous tumor of the omentum simulating a malignant ovarian tumor, which ultimately resulted to be a primary solitary fibrous tumor of the omentum. Ultrasound findings are mostly precise prognostic tools according ovarian masses. However, from time to time, Doppler blood flow examination may present false positive results.

Sofoudis C, Kouiroukidou P, Louis K, et al.
Enormous ovarian fibroma with elevated Ca-125 associated with Meigs' syndrome. Presentation of a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):142-3 [PubMed] Related Publications
In medicine, Meigs' syndrome is the triad of ascites, pleural effusion, and benign ovarian tumor (fibroma, Brenner tumour, and occasionally granulosa cell tumour). It resolves after the resection of the tumor. Because the transdiaphragmatic lymphatic channels are larger in diameter on the right, the pleural effusion is classically on the right side. The etiologies of the ascites and pleural effusion are poorly understood. Atypical Meigs' syndrome,characterized by a benign pelvic mass with right-sided pleural effusion but without ascites, can also occur. As in Meigs syndrome, pleural effusion resolves after removal of the pelvic mass. The authors would like to share their own experience of a case of Meigs' syndrome associated with an enormous ovarian fibroma and elevated Ca-125.

Kuno I, Hashiguchi Y, Kasai M, et al.
Krukenberg tumor in a 18-year-old-female: a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):139-41 [PubMed] Related Publications
BACKGROUND: Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare.
CASE: A 18-year-old female presented with colon cancer which was accompanied by Krukenberg tumor. The present case was a very rare case of metastatic ovarian tumor in very young age. The present patient presented with abdominal pain. On examination, colon tumor was detected and bilateral ovary were almost normal with only slight swelling. During the operation for colon tumor, biopsy of bilateral ovary was performed for histopathological evaluation. Although there were no specific findings in bilateral ovary, microscopic examination revealed poorly differentiated adenocarcinoma, diffusely invading the ovarian parenchyma. Diagnosis of colon cancer was made postoperatively and ovarian Krukenberg tumor was confirmed.
CONCLUSION: In case of suspecting colon cancer even in very young patient with normal ovary, biopsy of ovary should be considered for the diagnosis of Krukenberg tumor.

Li X, Yang J, Wang X, et al.
Role of TWIST2, E-cadherin and Vimentin in epithelial ovarian carcinogenesis and prognosis and their interaction in cancer progression.
Eur J Gynaecol Oncol. 2016; 37(1):100-8 [PubMed] Related Publications
UNLABELLED: Globally, most patients are at late-stage when they have been diagnosed with ovarian cancer. Investigating the potential mechanisms involved in tumor progression and prognosis is essential for improving treatment options, outcomes, and survival.
OBJECTIVE: This study elucidated the clinico-pathological significance of TWIST2 and the relationship of TWIST2, E-cadherin, and Vimentin expression in the progression and prognosis of epithelial ovarian cancer (EOC).
MATERIALS AND METHODS: Immunohistochemical staining was used to quantify the expression and relevance of TWIST2, E-cadherin, and Vimentin in 103 ovarian specimens, including 30 cases of benign ovarian tumors, 30 cases of borderline ovarian tumors, and 43 cases of EOC.
RESULTS: The expression of TWIST2 in the cytoplasm may help to maintain characteristics of epithelial cancer cells with E-cadherin normal membranous expression, while nuclear TWIST2 induces tumor translation front with membranous expression of Vimentin, which eventually promotes cancer metastasis. Moreover, the upregulation of TWIST2 was also related to the aberrant expression of E-cadherin and the increased expression of Vimentin, which were reported as important indicators of epithelial-mesenchymal transition (EMT).
DISCUSSION: The data suggested that co-expression of TWIST2/Vimentin was an independent prognostic indicator for both overall survival and disease-free survival by multivariate Cox proportional hazards model. TWIST2 regulates EMT by depriving the epithelial cell phenotype of E-cadherin and endowing the mesenchymal cell phenotype with Vimentin, which may be involved in the progression and prognosis of ovarian cancer, and TWIST2/Vimentin co-expression might be a novel indicator with prognostic potential in EOC patients.

Ma X, Hui Y, Lin L, et al.
Possible relevance of tumor-related genes mutation to malignant transformation of endometriosis.
Eur J Gynaecol Oncol. 2016; 37(1):89-94 [PubMed] Related Publications
OBJECTIVE: Despite studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood so far. Endometriosis-associated ovarian cancer (EAOC) or ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, the authors analysed mutations of tumour-related genes (PTEN and p53) in EAOC cases (n=23, group 1), including 19 cases which were detected co-existence of endometriosis and cancer and four cases which fulfilled the histological criteria in malignant transformation of endometriosis (OCEMs), and in atypical hyperplasia ovarian endometriosis (aEMs) (n = 10, group 2), as well as in solitary ovarian endometriosis (EMs) (n = 20, group 3), simultaneously, to study the correlation of the two genes in the development and progression of the ovarian endometriosis malignancy.
MATERIALS AND METHODS: Each paraffin block was sliced into serial ten-µm-thick sections. Extracted DNA was amplified by nested PCR. Mutations of PTEN and p53 were examined by bidirectional DNA sequencing.
RESULTS: It was acknowledged by experiments that the PTEN and p53 mutation frequency in EAOCs were significantly higher than that in aEMs and EMs. There was significant difference to compare EAOCs with EMs (p < 0.01, p < 0.05), and converse to compare with aEMs (p > 0.05), respectively. No definite involvement between the frequency of PTEN and p53 mutations in EAOCs and age difference, histological type, clinical stage, pathological grade, and whether accompanied by metastasis (p > 0.05); however, a decreasing trend of PTEN mutation with the increased age, decreased clinical stage and pathological grade, and when accompanied by metastasis was detected. Adversely, an increasing trend of p53 mutation was represented. In EAOCs group, the authors detected eight PTEN and four p53 mutation events, respectively. Moreover, one case occurred PTEN and p53 mutation simultaneously. With 23 EAOCs, two cases which fulfilled the histological criteria in malignant transformation of endometriosis, which may be a specific entity distinct from non-endometriosis-associated ovarian cancer, the authors named them the OCEMs, occurred PTEN or p53 mutation, respectively.
CONCLUSION: The present study suggested that the mutation and functional incapacitation of certain tumor-related genes may be involved in malignant transformation of endometriosis. PTEN mutation is the pristine event, but p53 mutation is the late.

Kanis MJ, Kolev V, Getrajdman J, et al.
Carcinosarcoma of the ovary: a single institution experience and review of the literature.
Eur J Gynaecol Oncol. 2016; 37(1):75-9 [PubMed] Related Publications
PURPOSE: To evaluate the management and outcome in patients with advanced stage primary carcinosarcoma (CS) of the ovary in a single institution.
MATERIALS AND METHODS: The authors performed a retrospective analysis of all patients treated for CS of the ovary between 1994 and 2011. The medical records, operative reports and pathology records were abstracted for baseline characteristics, surgical staging, degree of cytoreduction and chemotherapy regimens used. Standard statistical methods for analysis of the data were used.
RESULTS: A total of 33 patients with ovarian CS were identified. Of these, 28 records were available for analysis. One patient was Stage I (3.5%), two were Stage II (11.1%), 20 were Stage III (71.4%), and five (17.9%) were Stage IV. The early stage (Stage I and II) patients were excluded from analysis. Of the 25 advanced stage (III and IV) patients, 21 (84.0%) were optimally cytoreduced to a residual disease of < one cm and four (16.0%) were suboptimally cytoreduced. The median progression free survival (PFS) and overall survival (OS) were ten and 21 months, respectively, for advanced stages. Twenty-one (75%) patients received adjuvant chemotherapy and 62% (13 of 21) of treated patients received paclitaxel/carboplatin (T/C) as first-line chemotherapy. The median PFS and OS were 15.6 and 31.7 months, respectively, for those treated with T/C. There was no.difference in PFS (p = 0.42) and OS (p = 0.91) between the patients who received T/C vs. other chemotherapy regimens as a first-line adjuvant chemotherapy. Patients with optimal cytoreduction had an improved PFS compared to those with suboptimal cytoreduction (ten vs. four monthsp = 0.015); however, there was no difference in OS (21 vs. 13 p = 0.117). The two-year OS was 48.0%. In the preset study, PFS was improved in patients who were optimally cytoreduced at the time of diagnosis.
CONCLUSION: T/C is an active regimen in the treatment of ovarian CS and has the potential to be the backbone for addition of biologic targeted therapies in the future. For advanced ovarian CS the authors recommend optimal cytoreductive surgery followed by T/C chemotherapy.

Nieuwenhuyzen-de Boer GM, Gerestein CG, Eijkemans MJ, et al.
Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.
Eur J Gynaecol Oncol. 2016; 37(1):63-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment.
MATERIALS AND METHODS: Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk.
RESULTS: 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups.
CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

Santotoribio JD, Garcia-de la Torre A, Cañavate-Solano C, et al.
Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian tumors.
Eur J Gynaecol Oncol. 2016; 37(1):26-9 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous ovarian cancer (MOC).
MATERIALS AND METHODS: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC.
RESULTS: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125.
CONCLUSIONS: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.

Bonilla-Musoles F, Cadete C, Raga F, et al.
HDLive ultrasound images of ovarian dermoid cysts: diagnostic accuracy.
Clin Exp Obstet Gynecol. 2016; 43(1):16-24 [PubMed] Related Publications
OBJECTIVE: To demonstrate that the use of 3D/4D HDLive increases the image quality in the diagnosis of benign cystic ovarian teratomas.
MATERIALS AND METHODS: 3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian cystic teratoma using vaginal 2D US. The following pathognomonic images of mature cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid levels; 4) dermoid mesh with hyperechogenic calcifications indicating the presence of bone, teeth, or other ectodermally-derived structure; 5) multiple mobile spherical structures (fat globules).
RESULTS: Dermoids present a wide spectrum of images depending on the predominant tissue type. In the vast majority of cases there are dense echogenic structures that correspond to complex masses of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone. If we catalogue all the images together, the pathognomonic of dermoid are: 1) cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine bands that correspond with hair inside sebum (four cases, 12.9%) and that may form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three cases, 11.5%).
CONCLUSIONS: HDLive U.S. provides some images of exceptional quality that enhance the definition of the structures of these tumors (fat, hair, cartilage, bone, etc.) compared to 2D/3D/4D.

Appel SJ, Cleiment RJ
Identifying Women at Risk for Hereditary Breast and Ovarian Cancer Syndrome Utilizing Breast Care Nurse Navigation at Mammography and Imaging Centers.
J Natl Black Nurses Assoc. 2015; 26(2):17-26 [PubMed] Related Publications
Approximately 5-10% of breast cancer cases appear in families at a higher rate and at an earlier onset than in the average population. Two known gene defects, BRCA1 and BRCA2, account for the majority of these hereditary related breast cancers. Additionally, BRCA1 and BRCA2 are related to the Hereditary Breast and Ovarian Cancer syndrome (HBOC), where risk for other related cancers are increased. Various health-care professional organizations provide guidelines that speak to the need for conducting risk assessments, but little research has been conducted focusing on the initial screening for this syndrome. This quality improvement project attempts to determine if Nurse Navigators can effectively perform the initial education and screening for HBOC syndrome within a mammography and women's breast imaging setting using a simplified patient history tool. E. M. Rodgers' Diffusion of Innovation model, a map of how new ideas and programs have become adopted and accepted, guided this project's development and implementation. Over the course of 8 weeks, 1,420 women seeking service at 3 mammography and imaging sites were given a new risk assessment tool for HBOC. Additionally, the use of Nurse Navigation to identify women who may be at risk for HBOC was implemented. Two populations seeking service at the study sites were evaluated: (1) women obtaining breast screening/imaging services and (2) women receiving breast biopsy results. Patients identified as "at-risk" were defined by evidence-based practice guidelines from the National Comprehensive Cancer Network and were referred for further genetic evaluation by a genetic professional. During this initial implementation of the HBOC risk assessment program, low participation of screening/imaging patients requesting HBOC education and evaluation occurred (129 screening patients or 9%). High rates of positive biopsy patients (5 patients or 34.7%) werefound to be at risk for HBOC compared to similar studies. Identifying HBOC risk at the time of breast biopsy results gave the opportunity to impact the timing and kind of surgical management of patients at risk for this syndrome.The Commission on Cancer (CoC), an arm of the American College of Surgeons, provides practice guideline standards and accreditation for cancer programs. Patients will become more familiar with being assessed for HBOC and other hereditary cancers during their annual health-care visits and more identification of patients at riskfor HBOC should occur as new CoC 2012 standards requiring hereditary cancer risk assessments for a cancer program's certification are enacted.

Sorafenib (NEXAVAR) and differentiated thyroid cancer. Toxic, and no proof of improved survival.
Prescrire Int. 2016; 25(168):37 [PubMed] Related Publications
Radiological progression was delayed by 5 months in one trial, but its design does not allow reliable analysis of survival. Numerous, sometimes serious, adverse effects occurred.

Hong CM, Ahn BC
Can calcified pulmonary metastases detected by (18)F-FDG PET/CT suggest the primary tumor?
Hell J Nucl Med. 2016 Jan-Apr; 19(1):10-2 [PubMed] Related Publications
Many calcified nodules are encountered on the (18)F-FDG PET/CT scan and even though most of them are benign, the possibility of calcified pulmonary metastases (CPM) should be considered. The CT portion can often differentiate benign diseases due to their morphology. Measuring SUVmax is very important. Understanding the mechanism of calcification in malignant metastatic pulmonary lesions may be useful to suggest their origin.

Ledermann JA, Embleton AC, Raja F, et al.
Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet. 2016; 387(10023):1066-74 [PubMed] Related Publications
BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer.
METHODS: In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase. Participants were randomly allocated (2:3:3), with five stratification factors and in alternating blocks, to receive placebo alongside chemotherapy and then placebo only maintenance (arm A; reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance). Patients continued treatment to progression or excessive toxic effects. The primary efficacy endpoint was progression-free survival between arms A and C. Efficacy analysis was by intention to treat. Safety was assessed in all patients who received the allocated study drug. This trial is registered with ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003.
FINDINGS: We randomly assigned 486 [corrected] women between Nov 13, 2007, and Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent to the 30mg safety phase. During a median of 19·5 months (IQR 14-26) follow-up, 113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C had disease progression. Median progression-free survival was 11·0 months (95% CI 10·4-11·7) in arm C and 8·7 months (7·7-9·4) in arm A (hazard ratio 0·56, 0·44-0·72, p<0·0001). 156 (90%) of 174 patients in arm B had disease progression, and median progression-free survival was 9·9 months (95% CI 9·4-10·5). Diarrhoea, neutropenia, hypertension, and voice changes were significantly more common, during chemotherapy with cediranib, and diarrhoea, hypothyroidism and voice changes were more common during maintenance. Poor compliance with cediranib was noted during maintenance treatment with toxic effects being the most common cause for discontinuation.
INTERPRETATION: Cediranib, when given orally with chemotherapy and continued as maintenance, yielded a meaningful improvement [corrected] in progression-free survival in women with recurrent platinum-sensitive ovarian cancer, albeit with added toxic effects. The positive results in ICON6 could provide women with a new therapeutic option for recurrent ovarian cancer. Assessment of the secondary endpoint of overall survival will need longer follow-up.
FUNDING: Medical Research Council, Cancer Research UK, Canadian Cancer Society Research Institute, Cancer Australia, National Gynecological Cancer Centre, and AstraZeneca.

Husen Y, Saeed MA, Siddiqui S
J Ayub Med Coll Abbottabad. 2015 Oct-Dec; 27(4):936-7 [PubMed] Related Publications
Acinar cell carcinoma is a rare tumour arising from pancreatic acinar cells. Typical radiological patterns associated with it may suggest the unusual diagnosis even before final confirmation by histopathology. We present a case of an 8 year old boy who presented to clinic with symptoms of abdominal pain without associated jaundice or vomiting. Imaging revealed an atypical mass arising from head of the pancreas. Histopathology confirmed the diagnosis of acinar cell carcinoma. An idea about atypical and rare pancreatic masses is necessary to help direct the diagnosis and guide the pathologist for suspecting atypical pathology.

Jaszczyński J, Wilk W, Kruczak A, et al.
Histopathological assessment of residual retroperitoneal mass removed in patients after chemotherapy for non-seminomatous germ cell tumours of the testis.
Pol J Pathol. 2015; 66(4):420-5 [PubMed] Related Publications
Between 1990 and 1999, 182 men were treated for non-seminomatous germ cell testicular tumours. In 24 of them after chemotherapy a residual retroperitoneal mass was removed. In 14 of them additional immunohistochemical (IHC) examinations using antibodies against cytokeratins, vimentin, PLAP, CD30, AFP, βhCG, p53, and MIB-1 were performed. We compared the results of those additional studies with the results of routine histopathological examination. Histological assessment revealed most frequently (ca. 54% of cases) non-neoplastic lesions, i.e. fibro-cystic, necrotic or inflammatory tumours and lymphatic tissue. In about 33% of cases, surviving live neoplastic cells were found.

Lacout A, Chevenet C, Marcy PY
Mummified Thyroid Syndrome.
AJR Am J Roentgenol. 2016; 206(4):837-45 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to highlight the various sonographic characteristics that should help to differentiate a restructured benign collapsed thyroid nodule from histologically proven thyroid carcinoma by different imaging means, including Doppler sonography, and fine-needle aspiration cytologic analysis.
CONCLUSION: Benign thyroid nodules may display morphologic changes over time, which can have misleading sonographic features suggestive of malignancy. Precise knowledge of certain sonographic imaging features, such as regular eggshell calcifications, peripheral hypoechoic or hypoechoic rim, posterior shadowing, and absence of intranodular vascularization, and meticulous comparison with previous images showing thyroid nodule shrinkage over time are useful for reaching the correct final diagnosis. Fine-needle aspiration cytologic assessment of such initially suspicious thyroid nodules and sonographic follow-up contribute to establishing the final diagnosis of benign thyroid findings. Knowledge of the elements described should help to identify the so-called mummified thyroid nodule and avert surgical excision.

Stanculeanu DL, Mosoiu D, Mihnea A, et al.
Actualities in Ovarian Cancer in the Perspective of 2015 (ASCO and ECCO).
Chirurgia (Bucur). 2016 Jan-Feb; 111(1):9-11 [PubMed] Related Publications
Ovarian cancer represents the 4-th reason of cancer related death in women, the majority of patients being diagnosed in advanced stages of the disease, (III-IV). The loco-regional advanced ovarian cancer should be considered a chronic disease, with multiple evolutionary relapses and where the adjuvant treatment is mandatory.The treatment of the disease is multidisciplinary and the oncologist is the centerpiece.

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