Authors' reply.

Cancer Causes Control. 2008 Nov 28;

Authors: Dragani TA, Zocchetti C

PMID: 19039673 [PubMed - as supplied by publisher]

Expression of obestatin and ghrelin in papillary thyroid carcinoma.

Mol Cell Biochem. 2008 Nov 28;

Authors: Karaoglu A, Aydin S, Dagli AF, Cummings DE, Ozercan IH, Canatan H, Ozkan Y

Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.

PMID: 19039650 [PubMed - as supplied by publisher]

Horner's syndrome as a complication of thyroidectomy: Report of a case.

Surg Today. 2008;38(12):1114-6

Authors: Cozzaglio L, Coladonato M, Doci R, Travaglini P, Vizzotto L, Osio M, Gennari L

We report a case of Horner's syndrome (HS) occurring as a complication after total thyroidectomy. Horner's syndrome is characterized by myosis, eyelid ptosis, enophthalmos, and lack of sweating, with vascular dilatation of the lateral part of the face, caused by damage of the cervical sympathetic chain. We found only 28 other reports of HS developing after thyroidectomy, and only seven of these patients recovered completely. Of the 495 thyroidectomies performed at our hospital between 1997 and 2007, only one (0.2%) was complicated by the development of HS. The patient was a 35-year-old woman who underwent total thyroidectomy for Basedow-Graves' disease. Horner's syndrome manifested on postoperative day 2, but without anhydrosis or vascular dilatation of the face, and the symptoms resolved spontaneously 3 days later. The possible causes of HS after thyroidectomy include postoperative hematoma, ischemia-induced neural damage, and stretching of the cervical sympathetic chain by the retractor. The prompt and complete recovery of this patient suggests that the cervical sympathetic chain was damaged by retractor stretching.

PMID: 19039637 [PubMed - in process]

Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation.

Int J Hematol. 2008 Nov 29;

Authors: Hiramatsu Y, Maeda Y, Fujii N, Saito T, Nawa Y, Hara M, Yano T, Asakura S, Sunami K, Tabayashi T, Miyata A, Matsuoka KI, Shinagawa K, Ikeda K, Matsuo K, Tanimoto M,

A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

PMID: 19039629 [PubMed - as supplied by publisher]

Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy.

Int J Hematol. 2008 Nov 29;

Authors: Abe A, Minami Y, Hayakawa F, Kitamura K, Nomura Y, Murata M, Katsumi A, Kiyoi H, Jamieson CH, Wang JY, Naoe T

Chronic myelogenous leukemia (CML) is effectively treated with imatinib mesylate (IM), a small molecule inhibitor of the BCR-ABL tyrosine kinase that is expressed in the entire hematopoietic compartment including stem cells (HSC) and progenitors in CML patients. While IM induces disease remission, it does not appear to eradicate BCR-ABL-positive stem cells. We investigated the residual CML cells in HSC and myeloid progenitors isolated using fluorescence-activated cell sorting after IM-therapy. Quantitative real-time polymerase chain reaction detecting BCR-ABL transcripts showed that CML progenitors were eradicated within 12 months while the BCR-ABL-positive HSC remained. However, IM-therapy continuation could significantly decrease the ratio of BCR-ABL to BCR also in the HSC population. Our results implicate that the sorted and purified stem cells are useful for more sensitive quantification of BCR-ABL-positive minimal residual disease.

PMID: 19039626 [PubMed - as supplied by publisher]

TGFB1 gene polymorphism Leu10Pro (c.29T>C), prostate cancer incidence and quality of life in patients treated with brachytherapy.

World J Urol. 2008 Nov 28;

Authors: Meyer A, Dörk T, Bogdanova N, Brinkhaus MJ, Wiese B, Hagemann J, Serth J, Bremer M, Baumann R, Karstens JH, Machtens S

OBJECTIVES: Transforming growth factor beta1 gene (TGFB1) variant Leu10Pro (L10P) has previously been implicated in prostate cancer risk and radiation-induced side-effects. We investigated whether prevalence of this polymorphism is increased in prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. METHODS: A series of 445 consecutive patients treated for early-stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between 10/2000 and 10/2007 at our institution and a comparison group of 457 healthy male control individuals were screened for TGFB1 L10P (869T>C) polymorphism. Morbidity was assessed prospectively and compared between carriers versus non-carriers using International Prostate Symptom Score (IPSS), disease-specific Quality-of-Life single question added to the IPSS and International Index of Erectile Function with its subgroups. RESULTS: The Leu/Leu genotype was found in 150 patients (34%) versus 180 controls (39%), the Pro/Pro genotype in 75 patients (17%) versus 65 controls (14%) and the Leu/Pro genotype in 220 patients (49%) versus 212 controls (46%) without any statistically significant differences between the two groups. There was a trend towards an increased prevalence of the L10P substitution among patients with a per allele odds ratio of 1.19 (95% CI 0.99-1.44; P = 0.08). After a median follow-up of 18 months (range 1-60 months) there were no statistically significant differences regarding morbidity. CONCLUSIONS: TGFB1 polymorphism L10P is not strongly associated with prostate cancer risk. After 18 months, there was no evidence for increased adverse radiotherapy responses in heterozygote or rare homozygote carriers. Longer follow-up may be necessary to detect a statistically significant difference.

PMID: 19039592 [PubMed - as supplied by publisher]

Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma.

Cancer Immunol Immunother. 2008 Nov 28;

Authors: Johansson CC, Egyházi S, Masucci G, Harlin H, Mougiakakos D, Poschke I, Nilsson B, Garberg L, Tuominen R, Linden D, Stolt MF, Hansson J, Kiessling R

PURPOSE: New prognostic markers are needed for malignant melanoma. Inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) have been described to correlate with progression of melanoma. Moreover, activating mutations in BRAF/NRAS oncogenes are often detected in melanoma. The BRAF/NRAS mutation status and expression of COX-2 and iNOS were examined to compare their prognostic value for overall survival (OS) in stage III malignant cutaneous melanoma. EXPERIMENTAL DESIGN: The expression of iNOS and COX-2 in metastatic lymph nodes from 21 rapidly progressing (OS from date of diagnosis of stage III disease </=14 months) and 17 slowly progressing (OS >/=60 months) stage III cutaneous melanoma patients was examined by immunohistochemistry. The presence of BRAF/NRAS mutations was analyzed using direct DNA sequencing. chi(2) exact trend test and logistic regression analysis were used for statistical analysis. RESULTS: Both iNOS (P = 0.002) and COX-2 (P = 0.048) alone significantly predicted OS. The BRAF/NRAS mutation status did not significantly differ between patient groups, although iNOS significantly (P = 0.013) correlated with BRAF mutation frequency. Furthermore, the odds ratio (OR) with respect to OS of iNOS (OR = 10.4) was higher than that of COX-2 (OR = 5.6) and was stable in the multivariate analysis of OS together with disease stage IIIB/C, ulceration, number of metastatic lymph nodes, and Breslow tumor thickness. CONCLUSION: Our data show that iNOS is an independent and stronger prognostic factor for OS in stage III malignant cutaneous melanoma than COX-2.

PMID: 19039588 [PubMed - as supplied by publisher]

Pathogenesis of myeloma bone disease.

Leukemia. 2008 Nov 27;

Authors: Roodman GD

Bone disease in multiple myeloma (MM) is characterized by lytic bone lesions, which can cause severe bone pain, pathologic fractures and hypercalcemia. However, the lytic bone disease in MM differs from that in other cancer patients who have lytic bone metastases. Although increased osteoclastic bone destruction is involved in MM and other tumors involving bone, in contrast to other tumors, once the MM tumor burden exceeds 50% in a local area, osteoblast activity is either suppressed or absent.(1) The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been a topic of intensive investigation over the last several years and will be reviewed in this article.Leukemia advance online publication, 27 November 2008; doi:10.1038/leu.2008.336.

PMID: 19039321 [PubMed - as supplied by publisher]

Influence of chemotherapy on the biodistribution of [(99m)Tc]hydrazinonicotinamide annexin V in cancer patients.

Q J Nucl Med Mol Imaging. 2008 Nov 28;

Authors: Rottey S, Van Den Bossche B, Slegers G, Van Belle S, Van De Wiele C

AIM: The aim of this study was to determine whether administration of chemotherapy interferes with the quantitative uptake of [(99m)Tc]hydrazinonicotinamide (HYNIC) annexin V in normal human tissues at 5-7 h and 40-44 h after treatment initiation. METHODS: Eleven cancer patients were prospectively included in this study after written informed consent. Five patients underwent two scintigraphic scans with [(99m)Tc]HYNIC annexin V within 40-44 h from each other without any treatment given in between (control group or group 1). Six other patients starting a new chemotherapy or bisphosphonate regimen (treated group or group 2) underwent a scintigraphic scan with [(99m)Tc]HYNIC annexin V pretreatment (within 1 week of treatment initiation) and at 5-7 h and 40-44 h following treatment initiation. Whole-body and organ-specific geometric mean counts, corrected for background activity, were obtained from regions of interest drawn on the earliest images and kept constant over all subsequent images per patient. Differences in whole-body and organ uptake between successive scans were assessed using non-parametric statistics. RESULTS: No significant differences in mean percentages of injected dose uptake in whole body or organ tissues were observed between scan 1 and scan 2 in the control group and between scan 1, 2, and 3 in the treated group. CONCLUSION: Prior administration of [(99m)Tc]HYNIC annexin V and administration of chemotherapy does not interfere with quantitative specific uptake in healthy human tissues when using a schedule of baseline and 5-7 h and 40-44 h post-treatment imaging.

PMID: 19039304 [PubMed - as supplied by publisher]

Imaging in multicentric Castleman's disease.

J HIV Ther. 2008 Sep;13(3):72-4

Authors: Barker R, Kazmi F, Bower M

Multicentric Castleman[']s disease (MCD) is an uncommon lymphoproliferative disorder that presents with fevers, anaemia and multifocal lymphadenopathy and nowadays is most commonly diagnosed in individuals infected with HIV-1. CT scan findings are not sufficiently reliable to establish a diagnosis of MCD which requires histological confirmation. Newer imaging techniques have therefore been studied in patients with HIV-associated MCD in an attempt to improve diagnostic accuracy. Preliminary findings suggest that FDG PET-CT may assist in the monitoring of disease activity in MCD along with familiar clinical and laboratory tools and the more recently introduced plasma HHV8 DNA viral load measurement.

PMID: 19039298 [PubMed - in process]

Disseminated Peritoneal Leiomyomatosis Responds to Systemic Chemotherapy.

Oncology. 2008 Nov 27;76(1):55-58

Authors: Lin YC, Wei LH, Shun CT, Cheng AL, Hsu CH

Leiomyomatosis peritonealis disseminata (LPD) is a rare disease entity characterized by multiple peritoneal tumors composed of benign but proliferative smooth muscle cells. Surgery is the mainstay treatment for LPD. We present a 50-year-old woman who had previously undergone several surgical resections including bilateral oophorectomy for recurrent LPD. Because of progressive tumors in the peritoneum and metastatic tumors in the liver and lungs, systemic chemotherapy with doxorubicin and dacarbazine was prescribed. Objective tumor response was achieved and sustained for 1 year. This case presentation suggests that systemic chemotherapy may be considered as a treatment option for LPD patients developing unresectable or metastatic disease.

PMID: 19039249 [PubMed - as supplied by publisher]

Carboplatin and Pegylated Liposomal Doxorubicin for Advanced Ovarian Cancer: Preliminary Activity Results of the MITO-2 Phase III Trial.

Oncology. 2008 Nov 27;76(1):49-54

Authors: Pignata S, Scambia G, Savarese A, Breda E, Sorio R, Pisano C, Lorusso D, Cognetti F, Vernaglia Lombardi A, Gebbia V, Scollo P, Morabito A, Signoriello G, Perrone F

Background: Based on the efficacy of pegylated liposomal doxorubicin (PLD) in relapsed ovarian cancer, we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer. Because of limited phase I and II data on PLD plus carboplatin in this setting, we conducted an interim activity analysis. Patients and Methods: Patients with stage 1c-IV epithelial ovarian cancer were randomized to carboplatin AUC 5 plus either paclitaxel 175 mg/m(2) or PLD 30 mg/m(2) every 3 weeks for 6 cycles. The interim activity analysis was planned according to a single-stage phase II design with an auspicated 50% response rate; 50 patients eligible for response assessment were required. Response was defined according to RECIST (Response Evaluation Criteria in Solid Tumors). Results: A complete response was achieved in 14 patients (28%) and a partial response in 20 (40%), which produced an overall response rate of 68%. The activity exceeded the minimum required for study continuation. Stable disease was reported in an additional 10 patients (20%). Conclusions: The adopted schedule of PLD plus carboplatin demonstrates activity as a first-line treatment for advanced ovarian cancer.

PMID: 19039248 [PubMed - as supplied by publisher]

The Shrinking Thyroid: How Does Thyroid Size Change Following Radiation Therapy for Laryngeal Cancer?

AJNR Am J Neuroradiol. 2008 Nov 27;

Authors: Miller-Thomas MM, Kumar AJ, Sellin RV, Azimpoor S, Ang KK

BACKGROUND AND PURPOSE: External beam radiation therapy (XRT) for head and neck cancer is known to induce hypothyroidism and cause morphologic changes in the thyroid gland. This retrospective study investigates change in the size of the thyroid gland detectable by CT after XRT for laryngeal cancer. MATERIALS AND METHODS: The measured width of the thyroid lobes in 61 patients treated nonsurgically with XRT for laryngeal cancer between 2000 and 2003 on posttherapy CT was compared with that on pretherapy CT. Absolute and percentage changes in measured thyroid width following XRT were analyzed according to chemotherapy administration and posttherapy thyroid function. RESULTS: Eighty-five percent (52/61) of patients had a decrease in the width of the thyroid gland. The average change in width measuring -4.7 mm and -13.8% (SD, 5.7 mm and 19.9%) occurred at an average of 758 days following completion of XRT (mean, 402-1534 days) and was significant (P = .002). Average change in width between hypothyroid patients (n = 19, -6.1 mm and -20.0% change) and euthyroid patients (n = 42, -4.1 mm and -11.1% change) was not significant (P = .20 absolute change and P = .11 percentage change). The average change in width between patients receiving chemotherapy (n = 31, -5.5 mm and -16.1% change) and patients not receiving chemotherapy (n = 30, -3.9 mm and -11.5% change) was not significant (P = .26 absolute change and P = .37 for percentage change). CONCLUSIONS: Most nonsurgical patients receiving XRT for laryngeal cancer have a significant decrease in the width of their thyroid glands detected on CT. The average change in the size of the thyroid gland does not differ when development of hypothyroidism or chemotherapy administration are considered.

PMID: 19039044 [PubMed - as supplied by publisher]