Endocrine Malignancies
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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).

Rotruck S, Wilson JT, McGuire J
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a case report.
AANA J. 2014; 82(2):140-3 [PubMed] Related Publications
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex procedure used for the treatment of various types of cancer. Specifically, HIPEC has shown success where treatment failure sites (metastases) thrive. A classic example of one such area is the peritoneal surface, which remains a prominent failure site for patients with gynecologic and gastrointestinal cancer. Traditionally, most patients with advanced stages of cancer have undergone palliative procedures as part of their treatment modality or had no surgery at all. With the advent of cytoreductive surgery with HIPEC, patients with peritoneal cancer have shown increased survival rates. Anesthetic complications are common during this procedure with disturbances in hemodynamics, coagulation, and respiratory gas exchange. A knowledge of what to anticipate anesthetically will guide the practitioner to achieve successful management during and after the case. In this case report, a 71-year-old woman was treated for stage Ill peritoneal and ovarian cancer by cytoreductive surgery with HIPEC.

Related: Ovarian Cancer

Blanco R, Rodríguez Villar D, Fernández-Pello S, et al.
Massive bilateral adrenal metastatic melanoma of occult origin: a case report.
Anal Quant Cytol Histol. 2014; 36(1):51-4 [PubMed] Related Publications
BACKGROUND: Adrenal gland involvement by metastatic melanoma can be found in up to 50% of patients with ocular or cutaneous melanomas. Since these tumors are not hormone secreting, they usually present with locally advanced disease.
CASE: We report on the presence of a bilateral massive metastatic adrenal melanoma in an 80-year-old, symptomatic woman with the initial clinical diagnosis of adrenal hemorrhage/carcinoma. Histological assessment of the bilateral adrenalectomy showed a massive malignant melanoma in the adrenal glands, consistent with metastasis. Following that diagnosis, thorough studies revealed no ocular, mucocutaneous or primary tumor. The presence of melanoma in both adrenal glands favors metastatic melanoma over a primary adrenal melanoma.
CONCLUSION: What makes this case rare is the unusually great size of the symptomatic bilateral malignant melanoma adrenal metastasis of occult primary with wide hemorrhagic and necrotic areas, which was probably responsible for the patient's acute symptoms. The search for the primary tumor may be exigent, and it might not even be present at the time of diagnosis. Confirmation at autopsy is advisable, however this may not always be feasible.

Related: Cancer of Unknown Primary

Varinot J, Ménégaux F, Bitker MO, Compérat E
Renal metastasis from thyroid carcinoma: a case report.
Anal Quant Cytol Histol. 2014; 36(1):46-50 [PubMed] Related Publications
BACKGROUND: Renal metastases of thyroid carcinomas occur rarely and represent about 3% of all metastases to the kidney, with only 23 single case study reports in the English language literature.
CASE: A 77-year-old man presented with gross hematuria. CT scan showed a posterior and cortico-sinusal mass in the right kidney measuring 5 x 3 cm. On gross examination the kidney was occupied by a lobulated mass measuring 4.5 cm in its greatest dimension. Microscopically, there was a papillary and follicular proliferation with colloid-like materials in the intrafollicular space. The strong positive immunohistochemical stain of thyroglobulin and thyroid transcription factor-1 confirmed the origin of thyroid gland and the diagnosis of renal metastasis of thyroid carcinoma.
CONCLUSION: Although rare, the renal metastasis of a thyroid carcinoma is a diagnostic to consider even if the renal mass is unilateral and the patient has no history of thyroid surgery. The main differential diagnostic is the primitive thyroid-like follicular carcinoma of the kidney. Immunohistochemistry often leads to the right diagnosis, which is crucial for the management of the patient. Renal metastases of thyroid carcinomas are rare and often present as a primitive unilateral renal mass.

Related: Thyroid Cancer

Mosteiro L, Corominas-Cishek A, Muñiz G, et al.
Ultrasound-guided endoscopic fine needle aspiration cytology in pancreatic lesions: a series of 43 cases with histologic correlation from a single institution.
Anal Quant Cytol Histol. 2014; 36(1):9-14 [PubMed] Related Publications
OBJECTIVE: To describe the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC) in pancreatic lesions.
STUDY DESIGN: During a 5-year period (2007-2011) a total of 391 patients with pancreatic lesions have been studied using EUS-FNAC, with 43 of them having cytohistological correlation with core biopsy or surgical specimens. The diagnostic performance of this technique with and without the pathologist in the endoscopy room has been compared.
RESULTS: On the cytological smears, adenocarcinoma was diagnosed in 13 (30.2%) cases and neuroendocrine neoplasm in 2 (4.6%). Six (13.9%) cases were considered suspicious for malignancy, 2 (4.6%) were solid pseudopapillary tumors, and 20 (46.5%) were negative. There were no mucin-producing cystic neoplasms in the cytological diagnostic approach. After the cytohistological correlation, 23 (53.5%) cases were true positive, 11 (25.5%) were true negative, and 9 (21%) were false negative. There were no false positive cases in the series. Diagnostic precision was 79%, sensitivity 71.18%, specificity 100%, positive predictive value 100%, and negative predictive value 55%. The diagnostic performance of this technique is significantly higher (p < 0.015) when the pathologist is present in the endoscopy room.
CONCLUSION: Our data support the usefulness and reliability of EUS-FNAC in the diagnosis of pancreatic lesions. In our experience, significantly better results are obtained when the pathologist takes an active part in the procedure.

Related: Cancer of the Pancreas Pancreatic Cancer

Kawada N, Tanaka S, Uehara H, et al.
Alteration of strain ratio evaluated by transabdominal ultrasound elastography may predict the efficacy of preoperative chemoradiation performed for pancreatic ductal carcinoma: preliminary results.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):480-3 [PubMed] Related Publications
BACKGROUND/AIM: We evaluated the usefulness of ultrasound-elastography (US-elastography) for prediction of therapy effect by measuring strain ratio (SR).
METHODOLOGY: Consecutive patients with resectable pancreatic ductal carcinoma who underwent US-elastography before and after neoadjuvant chemoradiation were included. Patients were classified into either response group or non-response group according to the histological evaluation of resected specimens. Serum carbohydrate antigen 19-9 (CA19-9), SR, and maximum standard uptake value (SUVmax) obtained from 18F-fuluoro-deoxy-D-glucose positron emission tomography and computerized tomography were measured before and after chemoradiation. Alteration rate of each parameter was compared between response group and non-response group.
RESULTS: Seven patients met the inclusion criteria. One patient was excluded from pancreatectomy because liver metastasis was found by laparotomy. Serum CA19-9 was not elevated for 2 patients throughout the chemoradiation. Three patients were classified into response group and the remaining three into non-response group. Alteration rate of CA19-9 and SR was shown to be grater in response group (26.83 +/- 19.69 vs. 4.87 +/- 4.25, and 3.61 +/- 2.40 vs. 1.39 +/- 0.20, respectively), whereas that of SUVmax was not (1.56 +/- 0.43 vs. 2.11 +/- 0.10).
CONCLUSIONS: Increase rate of SR may predict the therapy effect of neoadjuvant chemoradiation for patients with pancreatic ductal carcinoma, especially for patients without elevation of tumor markers.

Related: Cancer of the Pancreas Pancreatic Cancer

Cao W, Zhou G, Qiu J, et al.
Research on the epigenetic modification of pancreatic cancer vaccine.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):272-7 [PubMed] Related Publications
Pancreatic cancer is characterized as a type of gastrointestinal tumor with a poor prognosis and high degree of malignancy. CIITA gene was found highly methylated in pancreatic carcinoma cell line PANC-1 and responsible for the low expression of MHC-II that may lead to immune evasion. Here, we tried to prepare pancreatic cancer vaccine with PANC-1 cells via epigenetic modification to enhance the MHC-II expression. Then the vaccine was injected into C57BL/6J mice and the effect was examined. Our study found that the vaccine could promote the proliferation of antigen-specific T cells, enhance the killing activity of cytotoxic lymphocytes (CTL), promote Th1-type cells mediated secretion of cytokines IFN-gamma and IL-2 while inhibiting Th2-type cells mediated secretion of IL-4, and inhibit the secretion of TGF-beta. Generally, the epigenetically modified vaccine could enhance the body's anti-tumor immune response, providing feasibility research on cancer vaccine for therapy of pancreatic cancer.

Related: Cytokines Cancer of the Pancreas Pancreatic Cancer

Kuroki T, Kitasato A, Adachi T, et al.
Single-incision laparoscopic distal pancreatectomy: our initial experience.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):212-4 [PubMed] Related Publications
BACKGROUND/AIMS: Single-incision laparoscopic surgery (SILS) is gaining popularity as a minimally invasive surgery. However, SILS distal pancreatectomy (SILS-DP) remains a challenging surgical procedure. In this study, we describe our initial experience with five cases of SILS-DP.
METHODOLOGY: We present an initial series of SILS-DP, performed between August 2010 and January 2013.
RESULTS: Five patients successfully underwent SILS-DP. The median operative time was 264 min (range, 232-345 min). The median intraoperative blood loss was 71 cc (range, 5-200 cc). All the patients left the hospital in good condition after SILS-DP.
CONCLUSIONS: Although SILS-DP is a safe, feasible, and esthetic procedure, a randomized controlled study is required to determine the advantages of SILS-DP in comparison with the standard laparoscopic method.

Related: Cancer of the Pancreas Pancreatic Cancer

Ueda J, Kayashima T, Mori Y, et al.
Hepaticocholecystojejunostomy as effective palliative biliary bypass for unresectable pancreatic cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):197-202 [PubMed] Related Publications
BACKGROUND/AIMS: The majority of patients with pancreatic cancer present with far advanced disease and jaundice. With the advancement of endoscopic interventional techniques, the role of surgical bypass has declined. However, surgical bypass is still considered to be appropriate in patients who are able to tolerate surgery. We performed hepaticocholecystojejunostomy consecutively as a palliative surgical biliary bypass for the purpose of long-term palliation. The aim of this study was to analyze the results of our palliative surgical biliary bypass, hepaticocholecystojejunostomy.
METHODOLOGY: Between January 2001 through December 2009, 69 patients received palliative surgical biliary bypass (bypass group) and 33 patients received endoscopic biliary stenting (stent group) for unresectable pancreatic cancers. Mortality, morbidity and survival between the two groups were compared.
RESULTS: There was no in-hospital death in the bypass group, but 2 patients (6%) in the stent group died in the hospital (p = 0.04). The surgical morbidity rate was 15% in the bypass group, while 20 patients (61%) in the stent group developed complications, mainly due to stent blockage. There was no significant difference in overall survival between the two groups. Among patients who underwent systemic chemotherapy but did not present with jaundice at the time of diagnosis, those who underwent prophylactic surgical biliary bypass before chemotherapy showed better survival than those who underwent systemic chemotherapy preceding biliary bypass or biliary stenting after occurrence of jaundice (p = 0.01).
CONCLUSIONS: Hepaticocholecystojejunostomy resulted in negligible mortality, low morbidity and effective long-term palliation. Prophylactic surgical biliary bypass with gastrointestinal bypass might be a good treatment option for non-jaundiced patients undergoing chemotherapy for unresectable pancreatic cancer.

Related: Cancer of the Pancreas Pancreatic Cancer

Josephides E, Gala A, Chowdhury S
GPs have key role in managing men with testicular cancer.
Practitioner. 2014; 258(1770):19-23, 2-3 [PubMed] Related Publications
Testicular cancer accounts for 1% of all malignancies in males. However, it is the most frequently occurring solid tumour in men between the ages of 15 and 34 years. Testicular germ cell tumours are classified into two main types: pure seminomas and non-seminomas which are also called non-seminomatous germ cell tumours (NSGCTs). NSGCTs are more clinically aggressive than seminomas so those patients who have both seminoma and non-seminoma components are managed according to NSGCT guidelines. Testicular tumours have excellent cure rates, even in those with metastases, as they are extremely sensitive to chemotherapy and radiotherapy. Early diagnosis is, however, very important as treatment is more successful and less intensive, and long-term health consequences can be minimised. Treatment options include surgery, chemotherapy, radiotherapy, or a combination of the above, depending on the histology, presence of tumour markers and radiological staging. In most patients, there is recovery of spermatogenesis two years after completion of chemotherapy but in all patients, sperm banking should be offered before chemotherapy. The risk of developing a secondary malignancy is increased in patients treated for testicular cancer. Men who have been treated with infradiaphragmatic radiotherapy or chemotherapy also have an increased incidence of cardiovascular disease and metabolic syndrome. Patients should be screened for cardiovascular risk factors, given healthy lifestyle advice and advised not to smoke.

Related: Germ Cell Tumors Testicular Cancer

Bombil I, Bentley A, Kruger D, Luvhengo TE
Incidental cancer in multinodular goitre post thyroidectomy.
S Afr J Surg. 2014; 52(1):5-9 [PubMed] Related Publications
BACKGROUND: The risk of malignancy in patients with multinodular goitre (MNG) is approximately 7.2%. The gold standard for diagnosis of thyroid cancer is fine-needle aspiration biopsy (FNAB). Unsuccessful, inconclusive or suspicious results mandate further investigations. The concern is that with a benign FNAB result there is no indication for surgery unless the patient has compression symptoms or cosmetic issues, but the risk of missed malignancy is nevertheless present.
OBJECTIVE: To determine the prevalence and histological features of incidental cancers in patients who had thyroidectomy for MNG.
METHOD: Records of patients who underwent thyroidectomy between January 2005 and December 2010 at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, were retrospectively reviewed. Data retrieved included demographic characteristics of the patients, type of thyroidectomy, thyroid function test results, FNAB cytology and final histology results.
RESULT: A total of 166 thyroidectomies were performed on 162 patients, the majority (139) of whom were females. The mean age was 46 years (range 15 - 79 years). A total of 120 pre-operative FNABs were available for analysis, 78 of which were suggestive of benign nodular goitre; 70 benign FNAB results were histologically confirmed to be MNG after thyroidectomy. Incidental malignancy was found in four of 70 cases of MNG (5.7%); all were papillary carcinomas, predominantly (75.0%) the follicular variant.
CONCLUSION: The risk of missing cancer in patients with MNG was 5.7%. The commonest histological subtype of thyroid cancer found in MNG was papillary carcinoma.

Related: Thyroid Cancer

Ahmed T, Kayani N, Ahmad Z, Haque MN
Non-Hodgkin's thyroid lymphoma associated with Hashimoto's thyroiditis.
J Pak Med Assoc. 2014; 64(3):342-4 [PubMed] Related Publications
We report two cases of thyroid lymphoma. First was of a 54-year-old lady who presented with a 10 year history of goiter. Examination revealed an enlarged thyroid gland extending sub-sternally, with no palpable lymph nodes. She had been on thyroxine for 4 months, due to a high TSH with positive antibodies. Fine needle aspiration cytology of thyroid showed Hashimoto thyroiditis (HT). A total thyroidectomy was done because of pressure symptoms. Histopathology revealed HT in right lobe and Diffuse Large B-cell Non-Hodgkin's lymphoma (DLBCL) in left lobe. Second case was of a 30 year-old man who presented with dyspnoea secondary to rapidly enlarging thyroid. On examination, thyroid was diffusely enlarged together with palpable lymph nodes. His TSH was elevated & Anti-TPO antibodies were positive suggesting an autoimmune etiology. Ultrasound showed, an ill-defined heterogeneous mass in the left lobe of thyroid gland with multiple enlarged lymph nodes. Ultrasound guided thyroid core biopsy revealed DLBCL.

Related: Non Hodgkin's Lymphoma Thyroid Cancer

Conzo G, Calò PG, Sinisi AA, et al.
Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: a retrospective study of a large clinical series.
Surgery. 2014; 155(6):998-1005 [PubMed] Related Publications
BACKGROUND: In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy.
METHODS: The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared.
RESULTS: The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups.
CONCLUSION: In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.

Related: Thyroid Cancer

Bockhorn M, Uzunoglu FG, Adham M, et al.
Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).
Surgery. 2014; 155(6):977-88 [PubMed] Related Publications
BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.
METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.
RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers.
CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

Related: Cancer of the Pancreas Pancreatic Cancer

Sato Y, Maekawa S, Ishii R, et al.
Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.
Science. 2014; 344(6186):917-20 [PubMed] Related Publications
Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.

Related: Adrenocortical Cancer Adrenocortical Carcinoma - Molecular Biology

Baandrup L, Friis S, Dehlendorff C, et al.
Prescription use of paracetamol and risk for ovarian cancer in Denmark.
J Natl Cancer Inst. 2014; 106(6):dju111 [PubMed] Related Publications
It has been suggested that paracetamol reduces the risk for ovarian cancer. We examined the association between prescription use of paracetamol and ovarian cancer risk in a nationwide case-control study nested within the Danish female population. Case patients (n = 3471) were all women with a first diagnosis of epithelial ovarian cancer during the period from 2000 to 2009. Population control subjects (n = 50576) were selected by risk set sampling. Data were derived from prescription and other nationwide registries. Conditional logistic regression was used to estimate odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for ovarian cancer associated with use of paracetamol or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). All statistical tests were two-sided. Use of paracetamol was associated with a reduced odds ratio for ovarian cancer (OR = 0.82; 95% CI = 0.74 to 0.92; P < .001) compared with nonuse, and the odds ratio decreased further with long-term (≥10 years), high-intensity paracetamol use (OR = 0.45; 95% CI = 0.24 to 0.86; P = .02). Use of nonaspirin NSAIDs was not associated with ovarian cancer risk.

Related: Ovarian Cancer

Lee JM, Hays JL, Annunziata CM, et al.
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses.
J Natl Cancer Inst. 2014; 106(6):dju089 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
METHODS: Eligible patients had measurable or evaluable disease, gBRCAm, and good end-organ function. A 3 + 3 dose escalation tested daily oral capsule olaparib (100 or 200mg every 12 hours; dose level1 or 2) with carboplatin area under the curve (AUC) on day 8 (AUC3 day 8), then every 21 days. For dose levels 3 to 6, patients were given olaparib days 1 to 7 at 200 and 400 mg every 12 hours, with carboplatin AUC3 to 5 on day 1 or 2 every 21 days; a maximum of eight combination cycles were permitted, after which daily maintenance of olaparib 400mg every12 hours continued until progression. Dose-limiting toxicity was defined in the first two cycles. Peripheral blood mononuclear cells were collected for polymorphism analysis and polyADP-ribose incorporation. Paired tumor biopsies (before/after cycle 1) were obtained for biomarker proteomics and apoptosis endpoints.
RESULTS: Forty-five women (37 OvCa/8 BrCa) were treated. Dose-limiting toxicity was not reached on the intermittent schedule. Expansion proceeded with olaparib 400mg every 12 hours on days 1 to 7/carboplatin AUC5. Grade 3/4 adverse events included neutropenia (42.2%), thrombocytopenia (20.0%), and anemia (15.6%). Responses included 1 complete response (1 BrCa; 23 months) and 21 partial responses (50.0%; 15 OvCa; 6 BrCa; median = 16 [4 to >45] in OvCa and 10 [6 to >40] months in BrCa). Proteomic analysis suggests high pretreatment pS209-eIF4E and FOXO3a correlated with duration of response (two-sided P < .001; Pearson's R (2) = 0.94).
CONCLUSIONS: Olaparib capsules 400mg every 12 hours on days 1 to 7/carboplatin AUC5 is safe and has activity in gBRCAm BrCa/OvCa patients. Exploratory translational studies indicate pretreatment tissue FOXO3a expression may be predictive for response to therapy, requiring prospective validation.

Related: Breast Cancer Carboplatin Ovarian Cancer

Zhou F, Ma M, Tao G, et al.
Detection of circulating methylated opioid binding protein/cell adhesion molecule-like gene as a biomarker for ovarian carcinoma.
Clin Lab. 2014; 60(5):759-65 [PubMed] Related Publications
BACKGROUND: Hypermethylation of the opioid binding protein/cell adhesion molecule-like (OPCML) gene is frequently observed in ovarian carcinoma. We evaluated the detection of circulating hypermethylated OPCML for detecting ovarian carcinoma and assessing its prognosis.
METHODS: We studied 85 tissue samples including 45 ovarian cancer tissues and 40 normal ovarian tissues and blood samples from 45 ovarian cancer patients and 20 healthy individuals. Bisulfite sequencing and methylation-sensitive restriction enzyme-PCR (MSRE-PCR) were used to detect the frequency of OPCML hypermethylation.
RESULTS: We detected that the frequency of OPCML hypermethylation for tissue and serum samples in ovarian carcinoma were 86.7% (39/45) and 80.0% (36/45), respectively, but none was detected in ovarian tissue and serum of healthy individuals. The frequency of OPCML hypermethylation in endometrioid carcinoma, serous cystadenocarcinoma, mucinous cystadenocarcinoma, clear cell carcinoma, and undifferentiated carcinoma were 80.0%, 85.5%, 50.0%, 80.0%, and 100%, respectively (p > 0.05). The frequencies of OPCML hypermethylation in patients were also different in terms of tumor differentiation degree. We detected hypermethylated OPCML in the sera of 50% of well differentiated, 62.5% of moderately differentiated, 93.1% of poorly differentiated tumors (p < 0.05). The frequency of OPCML hypermethylation at FIGO stage I was 42.9%, stage II was 66.7%, stage III was 85.7%, stage IV was 100% (p < 0.05).
CONCLUSIONS: Detection OPCML methylation in the serum is useful for ovarian carcinoma diagnosis.

Related: Ovarian Cancer

Williams AR, Hammer GD, Else T
Transcutaneous biopsy of adrenocortical carcinoma is rarely helpful in diagnosis, potentially harmful, but does not affect patient outcome.
Eur J Endocrinol. 2014; 170(6):829-35 [PubMed] Related Publications
CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The utility, sensitivity, and effect on patient outcome of transcutaneous adrenal biopsy (TAB) for single, large, adrenal masses are unclear.
OBJECTIVE: This study evaluated the utility, diagnostic sensitivity, and effect on patient outcome of TAB in patients with ACC.
DESIGN AND SETTING: We conducted a retrospective review of the electronic medical records of all ACC patients who were evaluated at the University of Michigan Health System from 1991 to 2011. We evaluated the sensitivity of TAB for tumors with the final pathological diagnosis of ACC. We compared the characteristics and survival of patients with stage I-III disease who underwent TAB with those who did not undergo TAB.
RESULTS: A total of 75 ACC patients with TAB were identified. Complications occurred in at least 11% of patients and were mainly associated with bleeding. The maximum sensitivity of the procedure in diagnosing ACC was 70%. For stage I-III patients, baseline characteristics, stage at diagnosis, and adjuvant treatment with mitotane or radiation were not significantly different between the TAB (n=36) and the non-TAB (n=254) groups. There was no significant difference in recurrence-free (P=0.7) or overall survival (P=0.7) between patients who underwent TAB and those who did not.
CONCLUSIONS: TAB of single, large, adrenal masses is usually unnecessary, exposes patients to risk, but does not affect recurrence-free or overall survival.

Related: Adrenocortical Cancer Adrenocortical Carcinoma - Molecular Biology Mitotane

Friebel TM, Domchek SM, Rebbeck TR
Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis.
J Natl Cancer Inst. 2014; 106(6):dju091 [PubMed] Related Publications
BACKGROUND: There is substantial variability in cancer risk in women who have inherited a BRCA1 or BRCA2 (BRCA1/2) mutation. Numerous factors have been hypothesized to modify these risks, but studies are of variable quality, and it remains unclear which of these may be of value in clinical risk assessment.
METHODS: PubMed and Web of Science databases were searched for articles published through September 2013. Fixed effects meta-analysis was done using the hazard ratios and/or odds ratios to estimate the pooled effect estimates (ES) and 95% confidence intervals (CIs) to identify factors that are associated with cancer risk modification in BRCA1/2 mutation carriers.
RESULTS: We identified 44 nonoverlapping studies that met predefined quality criteria. Sufficient evidence is available to make clinically relevant inferences about a number of cancer risk modifiers. The only variable examined that produced a probable association was late age at first live birth, a meta-analysis showed a decrease in the risk of breast cancer in BRCA1 mutation carriers with women aged 30 years or older vs. women younger than 30 years (ES = 0.65; 95% CI =0.42 to 0.99). The same was shown for women aged 25 to 29 years versus those aged less than 25 years (ES = 0.69; 95% CI = 0.48 to 0.99). Breastfeeding and tubal ligation were associated with reduced ovarian cancer risk in BRCA1 mutation carriers; oral contraceptives were associated with reduced risk among BRCA1/2 mutation carriers. Smoking was associated with increased breast cancer risk in BRCA2 mutation carriers only.
CONCLUSIONS: Data assessing many potential risk modifiers are inadequate, and many have not been externally validated. Although additional studies are required to confirm some associations, sufficient information is available for some risk factors to be used in risk counseling or lifestyle modification to minimize cancer risk in BRCA1/2 mutation carriers

Related: Breast Cancer Ovarian Cancer

Rinaldi S, Plummer M, Biessy C, et al.
Thyroid-stimulating hormone, thyroglobulin, and thyroid hormones and risk of differentiated thyroid carcinoma: the EPIC study.
J Natl Cancer Inst. 2014; 106(6):dju097 [PubMed] Related Publications
BACKGROUND: Increased levels of thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) are associated with differentiated thyroid carcinoma (TC) risk, but strong epidemiological evidence is lacking.
METHODS: Three hundred fifty-seven incident TC case patients (n = 300 women and 57 men; mean age at blood collection = 51.5 years) were identified in the EPIC cohort study and matched with 2 (women) or 3 (men) control subjects using incidence density sampling. Matching included study center, sex, age, date, time, and fasting status at blood collection. Levels of total and free (f) thyroxine (T4) and triiodo-thyronine (T3), TSH, Tg, and anti-Tg antibodies (TgAb) were measured by commercially available immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. All statistical tests were two-sided.
RESULTS: TC risk was positively associated with Tg (OR for the highest vs lowest quartile = 9.15; 95% CI = 5.28 to 15.90; P < .001) and negatively associated with TSH level (OR = 0.56; 95% CI = 0.38 to 0.81; P = .001). Odds ratios were not modified by adjustment for weight and height and were consistent across sexes, age groups, and countries. The association with Tg was stronger in follicular than papillary TC. The odds ratio for TgAb-positivity was 1.50 (95% CI = 1.05 to 2.15; P = .03). Among case patients, TSH level was stable over time, whereas Tg level was higher in proximity to TC diagnosis. Areas under the receiver operating characteristic curve were 57% and 74% for TSH and Tg level, respectively.
CONCLUSIONS: High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease. Low TSH levels may predispose to TC onset. Neither marker has sufficient accuracy to be a screening test.

Related: Thyroid Cancer

Rabban JT, Garg K, Crawford B, et al.
Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.
Am J Surg Pathol. 2014; 38(6):729-42 [PubMed] Related Publications
Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

Related: Cancer Screening and Early Detection Fallopian Tube Cancer MKI67 TP53

Chan KK, Leung TH, Chan DW, et al.
Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer.
J Endocrinol. 2014; 221(2):325-36 [PubMed] Related Publications
Ovarian cancer cells express both estrogen receptor α (ERα) and ERβ, and hormonal therapy is an attractive treatment option because of its relatively few side effects. However, estrogen was previously shown to have opposite effects in tumors expressing ERα compared with ERβ, indicating that the two receptor subtypes may have opposing effects. This may explain the modest response to nonselective estrogen inhibition in clinical practice. In this study, we aimed to investigate the effect of selectively targeting each ER subtype on ovarian cancer growth. Ovarian cancer cell lines SKOV3 and OV2008, expressing both ER subtypes, were treated with highly selective ER modulators. Sodium 3'-(1-(phenylaminocarbonyl)-3,4-tetrazolium)-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay revealed that treatment with 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP) (ERα antagonist) or 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) (ERβ agonist) significantly suppressed cell growth in both cell lines. In contrast, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) (ERα agonist) or 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]-pyrimidin-3-yl]phenol (PHTPP) (ERβ antagonist) significantly enhanced cell growth. These results were confirmed on a xenograft model where SKOV3 cells were injected s.c. into ovariectomized mice. We observed that the average size of xenografts in both the DPN-treated group and the MPP-treated group was significantly smaller than that for the vehicle-treated group. In addition, we found that phospho-AKT expressions in SKOV3 cells were reduced by 80% after treatment with MPP and DPN, indicating that the AKT pathway was involved. The combined treatment with MPP and DPN had a synergistic effect in suppressing ovarian cancer cell growth. Our findings indicate that targeting ER subtypes may enhance the response to hormonal treatment in women with ovarian cancer.

Related: Ovarian Cancer

Dimov RS, Kantchev RI, Boev BG, et al.
Laparoscopic resection of the pancreatic tail with preservation of the spleen in a patient with a large pseudopapillary tumor of the pancreas.
Folia Med (Plovdiv). 2014 Jan-Mar; 56(1):56-9 [PubMed] Related Publications
Laparoscopic resections of the pancreas have gained in popularity in the last few years. Those preserving the integrity of the spleen are performed very rarely and are a challenge for every surgeon. We hereby report a case of laparoscopic resection of the pancreatic tail with preservation of the spleen and the integrity and the blood supply to the spleen in a 26 year-old patient with a large pseudopapillary tumor of the pancreas. Postoperative recovery was quick and without complications. The functional and aesthetic result was satisfactory. Laparoscopic resection of the pancreas is a safe and effective therapeutic procedure in selected patients.

Related: Cancer of the Pancreas Pancreatic Cancer

Qiang W, Jin T, Yang Q, et al.
PRIMA-1 selectively induces global DNA demethylation in p53 mutant-type thyroid cancer cells.
J Biomed Nanotechnol. 2014; 10(7):1249-58 [PubMed] Related Publications
The p53 tumor suppressor pathway blocks carcinogenesis by triggering apoptosis and cellular senescence in response to oncogenic stress. Over 50% of human cancers including thyroid cancer carry loss-of-function mutations in the p53 gene. Recently, the identification of mutant p53-reactivating small molecules such as PRIMA-1 (p53 reactivation and induction of massive apoptosis) renders possibilities for the development of more efficient anticancer drugs. Although PRIMA-1 has been widely used for cancer therapy and exhibits a promising anticancer activity, its biological effect, particularly the epigenetic aspect, remains to be well elucidated. The present study attempts to explore the effect of PRIMA-1 on DNA methylation in a panel of thyroid cancer cell lines using luminometric methylation assay (LUMA). Our results showed that only p53 mutant-type cells were inhibited upon PRIMA-1 treatment. Conversely, p53 wild-type cells were non-sensitive to PRIMA-1. Moreover, our data demonstrated that PRIMA-1 selectively induced significant global DNA demethylation in p53 mutant-type cells. Mechanically, PRIMA-1 induced global DNA demethylation in these cells mainly through inhibiting the expression of DNA methyltransferase (DNMT) 1, 3a and 3b, and upregulating the expression of GADD45a. Notably, PRIMA-1 dramatically increased the expression of the ten-eleven translocation (TET) family of 5mC-hydroxylases, particularly TET1, in p53 mutant-type cells, further contributing to DNA demethylation. Thus, this study uncovered a previously unrecognized and prominent biological effect of PRIMA-1 through which it can cause global DNA demethylation in p53 mutant-type cancer cells mainly by rescuing the function of mutant p53 protein.

Related: CDKN1A Thyroid Cancer TP53 TET1

Oliver A, Overton C
Detecting ovarian disorders in primary care.
Practitioner. 2014; 258(1769):15-9, 2 [PubMed] Related Publications
Ovarian cysts occur more often in premenopausal than postmenopausal women. Most of these cysts will be benign, with the risk of malignancy increasing with age. The risk of a symptomatic ovarian cyst in a premenopausal female being malignant is approximately 1:1,000 increasing to 3:1,000 at the age of 50. Ovarian cysts may be asymptomatic but presenting symptoms include pelvic pain, pressure symptoms and discomfort and menstrual disturbance. Functional cysts in particular can be linked with irregular vaginal bleeding or menorrhagia. Ovarian torsion is most common in the presence of an ovarian cyst. Dermoid cysts are most likely to tort. Torsion presents with sudden onset of severe colicky unilateral pain radiating from groin to loin. There may be nausea and vomiting. It is often confused with ureteric colic where the pain is similar but radiates loin to groin. Symptoms which may be suggestive of a malignant ovarian cyst, particularly in the over 50 age group, include: weight loss, persistent abdominal distension or bloating, early satiety, pelvic or abdominal pain and increased urinary urgency and frequency. CA125 levels should be checked in women who present with frequent bloating, feeling full quickly, loss of appetite, pelvic or abdominal pain or needing to urinate quickly or urgently. Symptomatic postmenopausal women, those with a cyst > or = 5 cm, or raised CA125 levels, should be referred to secondary care. Functional cysts, particularly when they are < 5 cm diameter, usually resolve spontaneously without the need for intervention. In premenopausal women simple cysts > or = 5 cm are less likely to resolve and need an annual ultrasound assessment as a minimum.

Related: Ovarian Cancer

Cruz-Galarza D, Pérez-Rodríguez O, Laboy-Torres J, Gutiérrez-Rivera S
An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.
Bol Asoc Med P R. 2014; 106(1):54-6 [PubMed] Related Publications
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

Related: Breast Cancer Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer

Hernán Martínez J, Figueroa-Núñez C, Mansilla-Letelier P, et al.
Young female with acromegaloid features and pituitary macroadenoma: what is your diagnosis?
Bol Asoc Med P R. 2014; 106(1):49-53 [PubMed] Related Publications
Pseudoacromegaly is a extremely rare condition previously described and characterized by acromegaloid changes, tissue overgrowth, without elevations in insulin-like growth factor or growth hormone as seen in Acromegaly. We present the case of a young female seen initially with acromegaloid features and a pituitary microadenoma. After work-up the patient was diagnosed as insulin-mediated pseudoacromegaly. Only a few cases of pseudoacromegaly has been reported and should always be considered when evaluating patients for acromegaloid features with negative biochemical and hormonal levels.

Related: Pituitary Tumors Breast cancer in pregnancy

Sneesby L
Home is where I want to die: Kelly's journey.
Contemp Nurse. 2014; 46(2):251-3 [PubMed] Related Publications
The definition of a 'good death' is centred on being peaceful, dignified and pain free. The preferred place of death has also been highlighted as an important concept in defining a good death (Cox, Almack, Pollack, & Seymour, 2011). Seventy percent of Australians express the desire to spend their last days at home. In reality only 16% of people die at home (Preferred Place of Death, 2008). With 10% of Australians dying in residential aged care facilities and approximately 20% in hospices, the rest die in hospitals (Parish et al., 2006). Family support and the family's care giving ability play a major role in determining whether a person is able to die at home. Other factors include the availability of medical and nursing care. This story has been written with the consent of Kelly's husband. All efforts have been made to maintain privacy and confidentiality: Pseudonyms have been used.

Related: Australia Ovarian Cancer

Saab M, Noureddine S, Abu-Saad Huijer H, Dejong J
Surviving testicular cancer: the Lebanese lived experience.
Nurs Res. 2014 May-Jun; 63(3):203-10 [PubMed] Related Publications
BACKGROUND: Testicular cancer is thought to have a great impact on its survivors, yet there has been limited literature on the topic globally and no literature on the topic in Lebanon and the Arab region.
OBJECTIVE: The purpose of this study was to explore the lived experience of Lebanese testicular cancer survivors and gain an in-depth understanding of the psychosexual aspect of their experience.
METHODS: A hermeneutic phenomenological approach with semistructured digitally recorded interviews and observational field notes was utilized. A purposive sample of Lebanese testicular cancer survivors, aged between 18 and 50 years, in remission for at least 3 years, and willing to share personal information was recruited. Interviews were transcribed verbatim in Arabic. Data saturation was achieved at the seventh interview; a total of eight informants were recruited. The opening question was, "Tell me about your life since you got treated for testicular cancer," and was followed by probing questions. Two to three weeks after the initial interview, informants were called to validate the investigators' primary analysis.
RESULTS: Six core themes emerged: cancer perception in the Lebanese culture; "do not show, do not tell"; cancer experience is a turning point; fertility, manhood, and relationships; coping with cancer; and preserved aspects of life.
DISCUSSION: The findings provide an in-depth understanding of the experience of Lebanese testicular cancer survivors with a focus on the psychosexual aspect of this experience. The results suggest the need to educate patients about testicular cancer and its effect on their fertility.

Related: Testicular Cancer

Okusaka T, Ikeda M, Fukutomi A, et al.
Safety, tolerability, pharmacokinetics and antitumor activity of ganitumab, an investigational fully human monoclonal antibody to insulin-like growth factor type 1 receptor, combined with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer: a phase 1b study.
Jpn J Clin Oncol. 2014; 44(5):442-7 [PubMed] Related Publications
OBJECTIVE: Previous Phase 1 studies have shown the acceptable safety profile of ganitumab-a fully human monoclonal antibody to insulin-like growth factor Type 1 receptor-in patients with advanced solid tumors. However, ganitumab 20 mg/kg in combination with gemcitabine had not been administered to patients with metastatic pancreatic cancer. To evaluate the safety, tolerability, pharmacokinetics and antitumor activity of ganitumab 20 mg/kg combined with gemcitabine 1000 mg/m(2) as first-line therapy in patients with metastatic pancreatic cancer, we conducted a Phase 1b study.
METHODS: Eligible patients were adults with previously untreated metastatic adenocarcinoma of the pancreas. Patients received gemcitabine 1000 mg/m(2) on Days 1, 8 and 15 plus ganitumab 20 mg/kg on Days 1 and 15 of each 28-day cycle. Gemcitabine was administered intravenously over 30-60 min. Ganitumab was administered intravenously over 60 min after completing gemcitabine infusion.
RESULTS: Six patients were enrolled and received the study treatment. All patients had thrombocytopenia and leukopenia. Other most common adverse events were neutropenia and nausea. One patient had a dose-limiting toxicity defined as Grade 3 neutropenia with fever. Exposure to ganitumab 20 mg/kg was not affected by the administration of gemcitabine. No apparent pharmacokinetic drug-drug interaction was observed. No anti-ganitumab antibodies were detected. Five patients had a measurable tumor region at baseline. Of these, four patients had a best response of stable disease.
CONCLUSIONS: Ganitumab 20 mg/kg combined with gemcitabine 1000 mg/m(2) was tolerable and showed an acceptable safety profile in patients with untreated metastatic pancreatic cancer.

Related: Monoclonal Antibodies Cancer of the Pancreas Pancreatic Cancer IGF1R Gemcitabine

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