Xing M, Alzahrani AS, Carson KA, et al.
Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer.
JAMA. 2013; 309(14):1493-501 [PubMed]

IMPORTANCE: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established.
OBJECTIVE: To investigate the relationship between BRAF V600E mutation and PTC-related mortality.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 1849 patients (1411 women and 438 men) with a median age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. MAIN OUTCOMES AND MEASURES: Patient deaths specifically caused by PTC.
RESULTS: Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) (P < .001) in BRAF V600E-positive vs mutation-negative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.43 [95% CI, 2.06-9.51]; adjusted HR, 1.46 [95% CI, 0.62-3.47]). In patients with distant tumor metastasis, deaths per 1000 person-years were 87.72 (95% CI, 62.68-122.77) vs 32.28 (95% CI, 16.14-64.55) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 2.63 [95% CI, 1.21-5.72]; adjusted HR, 0.84 [95% CI, 0.27-2.62]).
CONCLUSIONS AND RELEVANCE: In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC.

Chandra SR, Shenoy RK, Karthikeyan, et al.
Rare treatable limb girdle muscle disease.
J Assoc Physicians India. 2012; 60:62-5 [PubMed]

We report two cases of Limb Girdle pattern of muscle weakness caused by hyperparathyroidism due to parathyroid adenoma. It can be easily missed as early symptoms are non specific but once diagnosed it is easily treatable and complete recovery occurs over a period of time.

Salehi P, Koh CJ, Pitukcheewanont P, et al.
Persistent Müllerian duct syndrome: 8 new cases in Southern California and a review of the literature.
Pediatr Endocrinol Rev. 2012 Dec-2013 Jan; 10(2):227-33 [PubMed]

Persistent Müllerian Duct Syndrome (PMDS) is a 46,XY disorder of sex development (DSD) in which Müllerian structures are found in genotypic males with normally virilized external genitalia and unilateral or bilateral cryptorchidism. It is usually diagnosed incidentally during surgical repair of cryptorchidism or inguinal hernia. The majority of cases are due to a mutation of the anti-Müllerian hormone (AMH) gene or the AMH receptor, type II (AMH-RII) gene. Management of patients with PMDS requires a multidisciplinary approach. Long-term prognosis is good although fertility appears to be decreased and there may be a risk of malignancy due to cryptorchidism and retained Müllerian remnants. We describe 8 new cases of PMDS diagnosed in Southern California in the past 10 years and review the literature.

Son J, Lyssiotis CA, Ying H, et al.
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.
Nature. 2013; 496(7443):101-5 [PubMed]

Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.

Pushkarev VM, Kovzun OI, Pushkarev VV, Tronko MD
Biochemical effects of combined action of gamma-irradiation and paclitaxel on anaplastic thyroid cancer cells.
Ukr Biokhim Zh. 2013 Jan-Feb; 85(1):51-61 [PubMed]

The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), gamma-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). IR activated common DNA damage-induced signaling and manifested certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There was clear antagonism between Ptx and IR relative to cell cycle regulators--tumor suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but combined action of both agents enhanced caspase-3 and, especially, caspase-8 activation. The Ptx at low (1-25 nM) concentrations caused noticeable radioprotective effect. Thus, in ATC cells the ionizing radiation and Ptx exhibited competitive effects upon phosphorylation of cell cycle controllers: p53, pRb, CHK2, cAbl and expression of Bax. At the same time, the combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases activation and survivin expression. The net effect of these events during the first 48-72 h of cells incubation can be considered as antiapoptotic--Ptx attenuated cytotoxic effect of IR.

Aich RK, Dasgupta S, Chakraborty B, et al.
Primary fallopian tube carcinoma with metastasis in the contralateral ovary.
J Indian Med Assoc. 2012; 110(7):494-5, 498 [PubMed]

Primary malignant neoplasm of the fallopian tube is one of the rarest gynaecological malignancies and a pre-operative diagnosis is often missed due to its diagnostic confusion with the tubo-ovarian mass, hydrosalpinx, ectopic pregnancy and ovarian malignancy. Transcoelomic, lymphatic, transluminal and haematogenous spread may occur to the other abdominal and pelvic organs as well as to the distant sites. Though the body of the uterus, ovaries and the contralateral fallopian tube are frequently involved, in the present case the contralateral ovary was the only site of involvement which is very unusual.

Bertsch T, Aschenneller C, Bewarder N, et al.
European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.
Clin Lab. 2013; 59(1-2):185-92 [PubMed]

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions.
METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically.
RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used.
CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

Gómez-Ramírez J, Tagarro D, Bravo JM, et al.
Preoperative parathyroid harpoon localisation: a new technique helpful in reoperative patients with persistent hyperparathyroidism.
Ann R Coll Surg Engl. 2013; 95(2):e25-6 [PubMed]

Surgery for persistent primary hyperparathyroidism remains a major challenge for surgeons and these reoperative procedures require an experienced parathyroid surgeon. The goal of reoperative surgery is to excise the abnormal parathyroid gland(s) and limit exploration to help minimise the potential complications. At least two positive and concordant localising studies should be available before reoperation because the technical difficulties in these cases make an exact localisation necessary before surgery. We describe the placement of a metallic harpoon under ultrasonography guidance as a safe, simple and inexpensive technique for localisation of the enlarged gland prior to conservative surgery.

Batisse M, Raverot G, Maqdasy S, et al.
Aggressive silent GH pituitary tumor resistant to multiple treatments, including temozolomide.
Cancer Invest. 2013; 31(3):190-6 [PubMed]

Temozolomide (TMZ) has been proposed as a therapeutic option in aggressive pituitary tumors. Among the published cases, GH expressing tumors were rare. We describe a patient with initially benign silent GH adenoma that transformed into an aggressive GH secreting tumor resistant to usual therapy. MGMT expression was high and the MGMT promoter was unmethylated. Before this aggressive course, patient received three cycles of TMZ; no response was observed. Four cases of GH aggressive tumor treated by TMZ have been reported. Response to TMZ was observed in one of these four patients. Predictive factors of failure of TMZ remain unclear.

Lim SD, Kim WS, Kwon GY
ROR2 and Wnt5a expression in stage 1 pure testicular seminomas.
Anal Quant Cytol Histol. 2013; 35(1):41-51 [PubMed]

OBJECTIVE: To elucidate the prognostic utility of several biomarkers including ROR2/Wnt5a in stage 1 pure seminoma, which is a highly curable tumor in need of prognostic markers to avoid unnecessary treatment.
STUDY DESIGN: A total of 47 patients of stage 1 seminoma who underwent radical orchiectomy were included in the study. Tissue microarray-based immunohistochemical analysis of placental alkaline phosphatase, D2-40, c-Kit, Oct-3/4, ROR2, Wnt5a, beta-catenin, CD30, vimentin, pancytokeratin, beta-hCG and p53 was conducted, and relevant clinicopathologic features were assessed.
RESULTS: ROR2 protein revealed strong diffuse membranous immunoreactivity (IR) in 12.8% and partial weak IR in 40.4%, respectively. Cytoplasimc Wnt5a IR was observed in 27.7%. ROR2 IR was correlated with Wnt5a IR (p = 0.029) and Oct3/4 IR (p = 0.035). c-Kit IR was correlated with Wnt5a IR (p = 0.034). No significant differences were found between ROR2/Wnt5a protein expression and the prognostically relevant features such as lymphatic invasion or pathologic T stage. Pathologic T stage was not correlated with rete invasion (p= 0.23). The expression or loss of other aforementioned antibodies was not associated with the prognostic clinicopathologic characteristics.
CONCLUSION: Our results do not support the relevance of ROR2/Wnt5a as biomarkers in stage 1 pure seminomas. The utility of the explored biomarkers as prognostic or differentiation indicators remains to be clarified.

Unlü S, Ozdemir S, Sümer S, et al.
Investigation of DNA damage by the alkaline comet assay in 131I-treated thyroid cancer patients.
Anal Quant Cytol Histol. 2013; 35(1):36-40 [PubMed]

OBJECTIVE: To assess the possible applicability of comet assay in the evaluation of DNA damage caused by ionizing radiation. The alkaline comet assay or single-cell gel electrophoresis has been used as a standard method for measuring and analyzing DNA damage.
STUDY DESIGN: Peripheral blood samples were collected from papillary thyroid cancer patients who received 131I by oral administration. Blood samples were taken just before the treatment, on the first day of treatment, and 1 week posttreatment. To determine the radiation-induced DNA damage, alkaline comet assay was performed.
RESULTS: It was found that significantly high levels of DNA damage occurred in first day samples when compared to control samples according to tail moment measurements. Also, a decrease in the level of damage was observed in the 1-week samples.
CONCLUSION: Our observations and data confirmed that treatment with 131I for papilloma thyroid cancer can cause DNA damage in circulating lymphocytes, and the comet assay seemed suitable to assess the effect of radioactive iodine for the patients.

Mweempwa A, Prasad J, Islam S
A rare neoplasm of the thyroid gland.
N Z Med J. 2013; 126(1369):75-8 [PubMed]

Burkitt's lymphoma of the thyroid gland is a rare malignancy. We present a case of a 58-year-old female who developed a rapid enlargement of her thyroid gland. Core biopsy confirmed the diagnosis of Burkitt's lymphoma. The tumour resolved after three cycles of chemotherapy. This case report emphasises the importance of considering lymphoma when dealing with thyroid nodules and goitres, as its management is different from that of other thyroid pathologies and delaying treatment has an impact on prognosis.

Liu X, Ma S, Dai C, et al.
Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor α-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells.
Endocrinology. 2013; 154(4):1414-23 [PubMed]

There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)α is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRα-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRα and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRα plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRα.

Pointer DT, Slakey LM, Slakey DP
Safety and effectiveness of vessel sealing for dissection during pancreaticoduodenectomy.
Am Surg. 2013; 79(3):290-5 [PubMed]

Traditional pancreaticoduodenectomy dissection techniques are tedious and time-consuming. The LigaSure(®) Vessel Sealing System is an alternative to standard dissection methods. LigaSure(®) can be used in replace of ligatures, clips, and sutures in most of the pancreaticoduodenectomy procedure. The objective of this study was to examine our experience with LigaSure(®) in pancreaticoduodenectomies and to show the safety and time-effectiveness. Forty-three pancreaticoduodenectomies were performed by a single surgeon using the LigaSure(®) device in place of traditional dissection techniques. A retrospective chart review was conducted to evaluate patient management and outcome. Demographics, preoperative, intraoperative, and postoperative data were analyzed. The average patient age was 61 years. Primary pathologic diagnoses were: periampullary carcinoma (56%), chronic pancreatitis (5%), cystic lesion (26%), neuroendocrine tumor (7%), and other (5%). Our patient population demonstrated American Society of Anesthesiologists Class I (2%), Class II (14%), III (75%), and IV (9%). Average operative time was 4:11 hours. The study group required an average of 0.49 ± 1.35 units of blood. Eight patients (19%) received blood transfusion, receiving an average of 2.63 ± 2.13 units. Patients had a median hospital stay of 10 days (range, 5 to 41 days). An oral diet was ordered for most patients by Day 4. Fourteen patients (32.5%) had a complication, including two patients requiring additional surgery for drainage of abscess. There were no postoperative deaths. The use of LigaSure(®) is a practical and safe alternative to standard dissection techniques. Operative time, blood loss, and complication rate are favorable compared with published series.

Kolačkov K, Tupikowski K, Bednarek-Tupikowska G
Genetic aspects of pheochromocytoma.
Adv Clin Exp Med. 2012 Nov-Dec; 21(6):821-9 [PubMed]

Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bβ, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view.

Al Rawahi T, Lopes AD, Bristow RE, et al.
Surgical cytoreduction for recurrent epithelial ovarian cancer.
Cochrane Database Syst Rev. 2013; 2:CD008765 [PubMed]

BACKGROUND: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival.
OBJECTIVES: To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly.
SELECTION CRITERIA: Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm.
DATA COLLECTION AND ANALYSIS: Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.
MAIN RESULTS: There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.Adverse events, quality of life and cost-effectiveness were not reported in any of the studies.
AUTHORS' CONCLUSIONS: In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Shylasree TS, Bryant A, Athavale R
Chemotherapy and/or radiotherapy in combination with surgery for ovarian carcinosarcoma.
Cochrane Database Syst Rev. 2013; 2:CD006246 [PubMed]

BACKGROUND: Ovarian carcinosarcoma, also known as malignant mixed Mullerian tumour, is a rare malignant gynaecological tumour constituting about 1% or less of all ovarian cancers. In over 80% of cases, there is extra-ovarian intra-abdominal spread at diagnosis. The primary treatment has traditionally been surgical cytoreduction followed by radiotherapy and chemotherapy or chemotherapy alone. Regimes have included cisplatin alone; a combination of doxorubicin, ifosfamide, dacarbazine, cyclophosphamide, taxol; and various other combinations. The effectiveness of these various regimens appears to be mixed. Therefore, there is a need to clarify if there is an optimum neoadjuvant or adjuvant therapy after surgical cytoreduction for this rare tumour. Also, it is important to address quality of life (QoL) issues related to treatment, particularly toxicity, as the overall prognosis appears to be poor.
OBJECTIVES: To assess the effectiveness and safety of various adjuvant and neoadjuvant chemotherapy and radiotherapy options or chemotherapy alone in combination with surgery in the management of ovarian carcinosarcoma.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field.
SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared neoadjuvant or adjuvant chemotherapy and radiotherapy, or chemotherapy alone, in women with ovarian carcinosarcoma (malignant mixed Mullerian sarcoma of the ovary). We also reviewed non-randomised studies (NRS) for discussion in the absence of RCTs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed.
MAIN RESULTS: The search strategy identified 297 unique references of which all were excluded.
AUTHORS' CONCLUSIONS: We found no evidence to inform decisions about neoadjuvant and adjuvant chemotherapy and radiotherapy regimens, or chemotherapy alone, for women with ovarian carcinosarcoma. Ideally, an RCT that is multicentre or multinational, or well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances, are needed to compare treatment modalities and improve current knowledge. Further research in genetic and molecular signalling pathways might improve understanding of this tumour subtype.

Lawrie TA, Medeiros LR, Rosa DD, et al.
Laparoscopy versus laparotomy for FIGO stage I ovarian cancer.
Cochrane Database Syst Rev. 2013; 2:CD005344 [PubMed]

BACKGROUND: This is an updated version of the original review that was first published in the Cochrane Database of Systematic Reviews 2008, Issue 4. Laparoscopy has become an increasingly common approach to surgical staging of apparent early-stage ovarian tumours. This review was undertaken to assess the available evidence on the benefits and risks of laparoscopy compared with laparotomy for the management of International Federation of Gynaecology and Obstetrics (FIGO) stage I ovarian cancer.
OBJECTIVES: To evaluate the benefits and risks of laparoscopy compared with laparotomy for the surgical treatment of FIGO stage I ovarian cancer (stages Ia, Ib and Ic).
SEARCH METHODS: For the original review, we searched the Cochrane Gynaecological Cancer Group Trials (CGCRG) Register, Cochrane Central Register of Controlled Trials (CENTRAL 2007, Issue 2), MEDLINE, EMBASE, LILACS, Biological Abstracts and CancerLit from 1 January 1990 to 30 November 2007. We also handsearched relevant journals, reference lists of identified studies and conference abstracts. For this updated review, we extended the CGCRG Specialised Register, CENTRAL, MEDLINE, EMBASE and LILACS searches to 6 December 2011.
SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and prospective case-control studies comparing laparoscopic staging with open surgery (laparotomy) in women with stage I ovarian cancer according to FIGO.
DATA COLLECTION AND ANALYSIS: There were no studies to include, therefore we tabulated data from non-randomised studies (NRS) for discussion.
MAIN RESULTS: We performed no meta-analyses.
AUTHORS' CONCLUSIONS: This review has found no good-quality evidence to help quantify the risks and benefits of laparoscopy for the management of early-stage ovarian cancer as routine clinical practice.

Zieliński G, Witek P, Koziarski A, Podgórski J
Spontaneous regression of non-functioning pituitary adenoma due to pituitary apoplexy following anticoagulation treatment - a case report and review of the literature.
Endokrynol Pol. 2013; 64(1):54-8 [PubMed]

Pituitary apoplexy (PA) is a rare, potentially life-threatening medical condition due to acute ischaemia or haemorrhage of the pituitary gland. The main clinical features are: abrupt onset of severe headache, nausea, vomiting, deteriorating level of consciousness, visual impairment and/or endocrine deficiency. Correct and prompt diagnosis is essential for effective therapy, but there are no randomised studies or strict recommendations defining treatment modalities. We present the case of a 59 year-old woman with pituitary tumour apoplexy, presenting with severe headache, vomiting and visual field deterioration. The patient was treated conservatively because of her refusal of surgery and was followed-up for five years. In the course of treatment, recovery of the visual field defects, as well as right sixth cranial nerve paresis, was observed. Repeated magnetic resonance imaging (MRI) revealed regression of the tumour without signs of its re-growth. We discuss therapeutic modalities with particular emphasis on morbidity and review the literature relating to the management of pituitary tumour apoplexy.

Le A, Shang L, Xiao T, et al.
Pheochromocytoma in ectopic pregnancy: a case report.
Clin Exp Obstet Gynecol. 2012; 39(4):553-5 [PubMed]

OBJECTIVE: To study pregnancy characteristics in women with pheochromocytoma and to improve awareness of this comorbidity among obstetricians and gynecologists.
METHODS: The diagnosis and treatment of a case of ectopic pregnancy with pheochromocytoma is described.
RESULTS: The patient was diagnosed with a ruptured left Fallopian tube isthmus due to pregnancy, with comorbid left adrenal pheochromocytoma.
CONCLUSION: Ectopic pregnancy with heavy bleeding and elevated blood pressure is indicative of pheochromocytoma. Measurement of the levels of urinary vanillylmandelic acid and urinary and serum catecholamines, as well as ultrasonography, can help diagnose this comorbidity.

Chentli F, Bey A, Belhimer F, Azzoug S
Spontaneous resolution of pituitary apoplexy in a giant boy under 10 years old.
J Pediatr Endocrinol Metab. 2012; 25(11-12):1177-9 [PubMed]

AIM: Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association.
OBSERVATION: A boy aged 9 years and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record has been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of visual acuity with diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient's brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient's vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH) = 39 ng/mL, n ≤ 5, prolactin ( PRL) = 470 ng/mL, n < 15]. Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor.
CONCLUSION: This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.

Peshev ZV, Borisov BB, Genova SN, Danev VH
Parathyroid carcinoma of the mediastinum.
Folia Med (Plovdiv). 2012 Oct-Dec; 54(4):80-3 [PubMed]

Parathyroid carcinoma accounts for about 4% of all diseases of the parathyroid glands. It usually presents as a tumor mass in the neck region. Mediastinal parathyroid carcinoma has been reported very rarely. The present paper reports an ectopic parathyroid carcinoma in the anterior mediastinum in a 54-year male that failed to be recognized antemortem. The markedly elevated serum calcium levels were repeatedly put down to laboratory errors, and the clinical features of primary hyperparathyroidism were misjudged and managed only symptomatically. The terminal cardiogenic shock was associated with myocardial infarction. Coronary plastic surgery was carried out and a stent was placed. The postmortem examination found a solid elastic tumor mass (4 cm) firmly encapsulated in the upper half of the anterior mediastinum having trabecular structure, mild nuclear and cellular polymorphism, single irregular mitoses and an area of necrosis. The mass invaded the capsule and the surrounding adipose tissue, there were tumor emboli found in the lymph and blood vessels. Immunohistochemical study showed diffuse expression of low molecular weight cytokeratin, chromogranin A and synaptophysin, and more than 20% of the tumor cells were Ki-67 positive. Glycogen granules were found in their cytoplasm. There were clearly seen metastatic calcifications in the intramural coronary vessels, the cardiomyocytes, the kidneys and the lungs. The present case report contributes considerably to the differential diagnosis of hypercalcemia.

Bunyavejchevin S, Phupong V
Laparoscopic surgery for presumed benign ovarian tumor during pregnancy.
Cochrane Database Syst Rev. 2013; 1:CD005459 [PubMed]

BACKGROUND: The surgical management of ovarian tumors in pregnancy is similar to that of non-pregnant women. The procedures include resection of the tumor (enucleation), removal of an ovary or ovaries (oophorectomy), or surgical excision of the fallopian tube and ovary (salpingo-oophorectomy). The procedure can be done by open surgery (laparotomy) or keyhole surgery (laparoscopy) technique. The benefits of laparoscopic surgery include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain. However, conventional laparoscopic surgery techniques required the infusion of gas carbon dioxide in the peritoneum to distend the abdomen and displace the bowel upward to create the room for surgical manipulation. Serious complications such as abnormally high levels of carbon dioxide in the circulating blood (hypercarbia) and perforation of internal organs have also been reported. These serious complication may be harmful to the fetus.
OBJECTIVES: To compare the effects of using laparoscopic surgery for benign ovarian tumor during pregnancy on maternal and fetal health and the use of healthcare resources.
SEARCH METHODS: We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 11 November 2012.
SELECTION CRITERIA: Randomized controlled trials with reported data that compared outcomes of laparoscopic surgery for benign ovarian tumor in pregnancy to conventional laparotomy technique.
DATA COLLECTION AND ANALYSIS: Two review authors planned to independently assess trial quality and extract data.
MAIN RESULTS: The updated search did not identify any randomized controlled trials.
AUTHORS' CONCLUSIONS: The practice of laparoscopic surgery for benign ovarian tumour during pregnancy is associated with benefits and harms. However, the evidence for the magnitude of these benefits and harms is drawn from case series studies, associated with potential bias. The results and conclusions of these studies must therefore be interpreted with caution.The available case series studies of laparoscopic surgery for benign ovarian tumour during pregnancy provide limited insight into the potential benefits and harms associated with this new surgical technique in pregnancy. Randomized controlled trials are required to provide the most reliable evidence regarding the benefits and harms of laparoscopic surgery for benign ovarian tumour during pregnancy.

North DL
Uptake of ¹³¹I in households of thyroid cancer patients.
Health Phys. 2013; 104(4):434-6 [PubMed]

Fifty persons and pets living with thyroid cancer patients who were treated with large administered activities of I have been surveyed to ascertain their uptake of radioiodine from the domestic environment. All patients had been hospitalized for one night after the therapeutic administration, and the thyroids of the cohabitants were assayed 3-10 d after the patients returned home. Seven of the assays were positive for I in the thyroid gland. The transmitted quantities absorbed by the cohabitants were all less than 10 of the patients' burdens at discharge.

Jiang W, Zeng ZC
Is it time to adopt external beam radiotherapy in the NCCN guidelines as a therapeutic strategy for intermediate/advanced hepatocellular carcinoma?.
Oncology. 2013; 84 Suppl 1:69-74 [PubMed]

OBJECTIVE: External beam radiotherapy (EBRT) is recommended as a therapeutic strategy for stage III hepatocellular carcinoma (HCC) in national guidelines of the Chinese Society of Liver Disease and in Korea Liver Cancer Study Group practice guidelines, but has not been considered a therapeutic option for HCC in Western countries. In this study, we review evidence supporting EBRT as an option for HCC treatment.
METHODS: Retrospective investigation was made of 775 patient records of intermediate/advanced HCC treated in our hospital during the last 10 years, including 98 patients with confined intrahepatic tumor, 181 with portal vein (PV) or inferior vena cava (IVC) tumor thrombi, 191 with lymph node metastases, 55 with adrenal gland metastases, 205 with bone metastases, 13 with lung metastases and 32 with brain metastases.
RESULTS: Transcatheter arterial chemoembolization combined with radiotherapy was found to constitute an improved therapeutic strategy for unresectable but confined intrahepatic HCC with poor lipid accumulation. Survival of HCC patients with PV/IVC tumor thrombi was prolonged to 10.7 months by radiotherapy, and it was 8.0 months in patients with abdominal lymph node metastasis. Radiotherapy also shrinks adrenal and lung metastatic HCC lesions, resulting in median survival times of 13.6 and progression-free survival of 13.4 months, respectively. In bone metastatic HCC, radiotherapy significantly relieved symptoms, although median survival time was only 7.4 months. Radiotherapy is effective for treatment of intermediate/advanced stages of HCC. Although our finding is based only on retrospective analysis, no therapeutic option that provides better treatment than EBRT in this indication has thus far been identified. Because sorafenib has been recommended as a treatment strategy by the National Comprehensive Cancer Network (NCCN) for HCC, we compared the survival after EBRT with sorafenib treatment on the basis of published clinical data. From this comparison, we found that EBRT treatment was more effective than sorafenib for improving patient survival when tested on tumors of comparable metastatic size.
CONCLUSION: Based on the evidence reviewed, we propose that EBRT be included in the NCCN guideline as a treatment strategy for intermediate/advanced HCC.

Volpe C, Höög A, Ogishima T, et al.
Immunohistochemistry improves histopathologic diagnosis in primary aldosteronism.
J Clin Pathol. 2013; 66(4):351-4 [PubMed]

BACKGROUND: In primary aldosteronism (PA) the main source of aldosterone hypersecretion is an aldosterone-producing adenoma (APA) or a bilateral hyperplasia. Histopathology of the adrenal gland from patients with PA has been difficult, as there are no morphological criteria to ascertain which are the cells that produce aldosterone. We therefore applied new specific antibodies to explore which cells in the adrenal contain the enzymes for aldosterone and cortisol production, respectively.
METHODS: Adrenals from 24 patients with PA were studied. After routine preparation, consecutive sections were stained with antibodies for CYP11B1 (cortisol) and CYP11B2 (aldosterone) enzymes.
RESULTS: APA had a strong immunoreactivity for CYB11B2. In adrenals from seven patients, we found no APA, but several nodules with strong CYB11B2 immunoreactivity, indicating aldosterone-producing nodular hyperplasia.
CONCLUSIONS: Immunohistochemistry of adrenal steroidogenic enzymes provides novel diagnostic information. This may become an important part of routine histopathology, and contribute to improved clinical management in PA.

Kawamoto S, Johnson PT, Shi C, et al.
Pancreatic neuroendocrine tumor with cystlike changes: evaluation with MDCT.
AJR Am J Roentgenol. 2013; 200(3):W283-90 [PubMed]

OBJECTIVE: The objective of our study was to determine the prevalence and CT appearance of cystlike changes of pancreatic neuroendocrine tumor (NET), particularly of small (≤ 3 cm) tumors.
MATERIALS AND METHODS: The clinical records, images, and pathologic reports of 74 consecutive patients (average age, 55.5 years) with surgically resected pancreatic NETs who underwent preoperative CT were retrospectively reviewed. The size and location of the pancreatic NETs were recorded. The tumors were classified on the basis of CT appearance as small (≤ 3 cm) or large (> 3 cm) and as solid, partially (≤ 50% or > 50%) cystic, or purely (≈ 100%) cystic. Peripheral contrast enhancement on CT was characterized, and lymph node and liver metastases found by pathologic examination were recorded.
RESULTS: A total of 78 pancreatic NETs were reviewed. Five were not visualized on CT, leaving 73 pancreatic NETs in 69 patients (multiple tumors were visualized on CT of three patients) for analysis. The mean size of the 73 tumors was 3.0 ± 2.6 (SD) cm (range, 0.7-13.1 cm); 52 tumors were 3 cm or smaller and 21 tumors were larger than 3 cm. Gross pathologic results confirmed that 13 of the 73 (17.8%) tumors were predominantly (> 50% or ≈ 100%) cystic: 10 of the 52 (19.2%) tumors 3 cm or smaller and three of the 21 (14.3%) tumors larger than 3 cm. Peripheral contrast enhancement was seen in 11 of the 13 (85%) predominantly cystic pancreatic NETs. Compared with solid pancreatic NETs, predominantly cystic pancreatic NETs were less commonly associated with lymph node and liver metastases.
CONCLUSION: Cystic pancreatic NETs are not rare and should be included in the differential diagnosis of a cystic pancreatic mass, particularly if the cystic mass is associated with peripheral contrast enhancement. A minority of cystic pancreatic NETs can present with no peripheral enhancement.

Tsili AC, Argyropoulou MI, Astrakas LG, et al.
Dynamic contrast-enhanced subtraction MRI for characterizing intratesticular mass lesions.
AJR Am J Roentgenol. 2013; 200(3):578-85 [PubMed]

OBJECTIVE: The objective of our study was to analyze the enhancement patterns of various intratesticular mass lesions at dynamic contrast-enhanced subtraction MRI and assess the value of the technique in distinguishing between benign and malignant lesions.
MATERIALS AND METHODS: We retrospectively evaluated the records and images of 44 consecutive men (11 benign and 16 malignant intratesticular lesions) who presented to the department of urology with a variety of clinical symptoms and were referred for imaging. Dynamic contrast-enhanced subtraction MRI was performed using a 3D fast-field echo sequence after the administration of paramagnetic contrast medium. Patients were divided into three groups according to the final diagnosis: benign intratesticular lesions, malignant intratesticular lesions, and normal testes. The patterns of contrast enhancement of both the normal testes and the intratesticular lesions were evaluated. Time-signal intensity plots were created and classified according to shape: Type I presented a linear increase of contrast enhancement throughout the examination, type II showed an initial upstroke followed by either a plateau or a gradual increase in the late contrast-enhanced phase, and type III presented an initial upstroke followed by gradual washout of the contrast medium. The relative percentages of peak height, maximum time, and mean slope were also calculated.
RESULTS: Normal testes enhanced homogeneously with a type I curve. Most benign intratesticular lesions showed inhomogeneous or homogeneous contrast enhancement and a type II curve. Testicular carcinomas showed heterogeneous contrast enhancement with a type III curve. The relative percentages of maximum time to peak proved the most important discriminating factor in differentiating malignant from benign intratesticular masses (p < 0.001).
CONCLUSION: Dynamic contrast-enhanced MRI may be used to distinguish between benign and malignant intratesticular mass lesions.

Raman SP, Kawamoto S, Blackford A, et al.
Histopathologic findings of multifocal pancreatic intraductal papillary mucinous neoplasms on CT.
AJR Am J Roentgenol. 2013; 200(3):563-9 [PubMed]

OBJECTIVE: The criteria for resection of solitary pancreatic side-branch intraductal papillary mucinous neoplasm (IPMN) have been well described by the Sendai consensus statement. However, the management of multiple pancreatic cystic lesions is less certain, with no clear guidelines in the literature to date. The purpose of this study was to evaluate the histopathologic findings in pancreatic IPMNs in patients with multiple (≥ 4) pancreatic cysts.
MATERIALS AND METHODS: The CT scans of all patients with a pathologically proven IPMN at our institution were reviewed, and a total of 52 patients with four or more pancreatic cysts were found. Each case was reviewed for the number of cysts and the presence of signs of invasive malignancy including a coexistent solid pancreatic mass, pancreatic ductal dilatation, and mural nodularity.
RESULTS: A total of 52 patients (19 men, 33 women; mean age, 71.8 years) were found to have multifocal IPMNs, defined as four or more cysts, on CT. Of these 52 patients, nine also had evidence of a solid pancreatic mass on CT. Retrospective review of the pathologic results for the remaining 43 patients (17 men, 26 women; mean age, 71.76 years) showed 18 cases of an IPMN with either high-grade dysplasia or a coexistent invasive carcinoma. Most important, 37% (7/19 patients) had no CT findings of an invasive malignancy according to the Sendai criteria (i.e., cysts ≥ 3 cm in the axial plane, main pancreatic ductal dilatation ≥ 6 mm, or mural nodularity within a cyst) but were found to have an IPMN with either high-grade dysplasia or invasive carcinoma. When the pancreas contained 10 or more cysts, high-grade dysplasia or invasive carcinoma tended to be more likely than low- or intermediate-grade dysplasia (odds ratio, 3.83; 95% CI, 0.87-16.8; p = 0.075).
CONCLUSION: The presence of multiple pancreatic cysts should be looked on with suspicion, particularly when there are a large number of cysts, even when none of the cysts individually meet the imaging criteria for resection according to the Sendai consensus recommendations. At the very least, these patients need to be followed very closely.

Yao JC, Phan AT, Jehl V, et al.
Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.
Cancer Res. 2013; 73(5):1449-53 [PubMed]

The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo.