Mixed medullary-papillary carcinoma of the thyroid: report of a case and review of the literature.

BACKGROUND: Mixed medullary-follicular thyroid carcinoma denotes a rare and heterogeneous group of tumors displaying morphological and immunophenotypical features of both origins within the same lesion. METHOD: We report a case of a 41-year-old woman with a lump in the right side of the neck, increasing in pain and size over several weeks. Serum levels of calcitonine (1140 ng/L) and carcinoembryonic antigen (288 microg/L) were very high. Fine-needle aspiration cytology suggested a diagnosis of medullary thyroid carcinoma. Total thyroidectomy, along with bilateral functional neck and mediastinal lymph-node dissection, were performed. RESULTS: The histopathological examination yielded a diagnosis of medullary carcinoma in the right thyroid lobe, closely intermingled with a nonencapsulated classical papillary carcinoma. One ipsilateral lymph node showed micrometastasis of the medullary counterpart. CONCLUSION: When compared with other cases reported in literature, this particular presentation should be recognized, if required, morphologic and functional criteria are used. The treatment is mostly surgical, driven by the medullary component. The presence of micrometastasis in 1 ipsilateral cervical lymph-node underlines the importance of cervicomediastinal lymph-node dissection and careful searching for metastatic disease.

Vitreoretinal surgery for complications of choroidal tumor biopsy.

OBJECTIVE: To determine the outcomes of vitreoretinal surgery after choroidal tumor biopsy. DESIGN: Retrospective, single-center, consecutive case series. PARTICIPANTS: A total of 739 consecutive patients undergoing choroidal tumor biopsy. METHODS: All subjects who underwent transretinal or transscleral choroidal tumor biopsy for diagnostic or prognostic purposes between May 1993 and May 2013 were identified in our database. We then reviewed patients who subsequently required secondary vitreoretinal surgery for complications arising from such biopsies. MAIN OUTCOME MEASURES: Reason for vitreoretinal surgery, association with biopsy procedure, best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR]), intraocular or extrascleral tumor dissemination, resolution of vitreous hemorrhage, reattachment of the retina with a single vitreoretinal procedure, number of additional vitrectomies undertaken, and number of enucleations. RESULTS: A total of 20 of 739 eyes (2.7%) underwent vitreoretinal surgery for complications arising from choroidal tumor biopsy. The tumors consisted of choroidal melanoma in all 20 eyes. The reasons for the secondary surgery included persistent vitreous hemorrhage in 1.9% (14/739), rhegmatogenous retinal detachment in 0.7% (5/739), and endophthalmitis in 0.14% (1/739). Median BCVA improved from 2.0 logMAR (mean, 1.92 logMAR; range, 0.8-2.7 logMAR) before vitrectomy to 0.72 logMAR (mean, 0.88 logMAR; range, -0.14 to 2.7 logMAR) after vitrectomy and 0.76 logMAR (mean, 1.14 logMAR; range, 0.1-3.0 logMAR) at the final visit (P < 0.0001, t test). Permanent resolution of vitreous hemorrhage was achieved in 6 of 14 patients, and reattachment of the retina was achieved in 2 of 5 patients after the first vitrectomy. A median of 1 (mean, 1.5; range, 1-3) additional vitrectomy was performed. Enucleation was necessary in 3 of 20 eyes (15%). There were no cases of intraocular invasion or extrascleral extension after vitrectomy. CONCLUSIONS: Vitrectomy for complications of choroidal tumor biopsy is rare. Such corrective surgery is complex and is best undertaken by specialized ocular oncologists or vitreoretinal surgeons with experience in managing this problem.

Nouvelles stratégies thérapeutiques en oncologie ophtalmo-pédiatrique [New strategies in pediatric ophthalmic oncology]

Le rétinoblastome représente 11% de tous les cancers apparaissant pendant la première année de vie. Pour éviter les effets secondaires de la chimiothérapie systémique ou de la radiothérapie externe, de nouveaux médicaments et de nouvelles techniques de traitement focalisé ont été développés. Des voies d'administration telles la voie périoculaire (topotécan) ou la voie artérielle ophtalmique directe (carboplatine) sont utilisées aujourd'hui dans certains cas résistants. La radiothérapie actuelle, appliquée exclusivement en deuxième intention, fait appel également à des techniques ciblées, permettant d'éviter les tissus sains et de réduire le risque de cancers radio-induits non oculaires. La radiothérapie stéréotaxique conformationnelle ou conformale et la proton-thérapie font ainsi partie du nouvel arsenal thérapeutique du rétinoblastome. Retinoblastoma represents 11% of all cancers during the first year of life. New drugs and focal treatments have been developed in order to avoid the side effects of systemic chemotherapy and external radiotherapy. New targeted and local administration strategies such as periocular chemotherapy (topotecan) or direct ophthalmic artery delivery (carboplatin), are already used today in selected resistant cases. Radiotherapy, presently indicated only as a second-line treatment, is also subject to new techniques, targeting tumors more closely to avoid involving healthy tissue and reduce the risk of radio-induced nonocular tumors. Stereotactic conformal radiotherapy and proton therapy may thus be included in the new range of treatment methods in retinoblastoma

Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.

Peroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes. However, PPARdelta's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARdelta decreases intestinal adenoma growth in Apc(Min/+) mice and inhibits tumor-promoting effects of a PPARdelta agonist GW501516. More importantly, we found that activation of PPARdelta up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARdelta agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer.

Infrequent expression of the MAGE gene family in uveal melanomas.

It has previously been reported that MAGE-1, -2, -3 and -4 genes are expressed in human cancers including cutaneous melanoma. MAGE-1 and MAGE-3 represent targets for specific immunotherapy because they encode peptide antigens which are recognised by cytotoxic T lymphocytes (CTL) when presented by HLA class I molecules, and pilot clinical trials with these peptides are currently in progress. It is likely that other members of the MAGE gene family may also encode antigens recognised by CTL. Uveal melanomas, like cutaneous melanomas, arise from melanocytes that are derived from the neural crest. To determine if uveal melanoma patients would be suitable for MAGE-peptide immunotherapy, the expression of MAGE-1, -2, -3 and -4 genes was assessed by reverse transcription followed by polymerase chain reaction (RT-PCR) amplification and ethidium bromide staining. Expression of MAGE genes was not detected in any of 27 primary tumours. Either MAGE-1 or MAGE-4 was expressed in only 2 of 26 metastatic samples, but expression of MAGE-2 or -3 was not detected. Our data suggest that, unlike cutaneous melanomas, uveal melanomas may not be suitable candidates for MAGE-peptide immunotherapy.

Small cell (neuroendocrine) carcinoma of the prostate: etiology, diagnosis, prognosis, and therapeutic implications--a retrospective study of 30 patients from the rare cancer network.

Within the framework of the Rare Cancer Network Study, we examined 30 patients suffering from small cell neuroendocrine prostate cancer, either in an early/localized or an advanced/metastatic stage. Patients were treated with cisplatin-based chemotherapy, with or without pelvic radiotherapy. Two patients with early disease achieved complete remission for a duration of 19 and 22 months. Three patients with advanced disease achieved complete remission for 6, 7, and 54 months, respectively. Twenty-five patients succumbed to massive local and/or distant failure. No patient presented with brain metastases as the initial site of relapse. Small cell neuroendocrine prostate carcinoma is a very aggressive disease with a poor prognosis, even in its localized form. Despite initial response, the common cisplatin-based chemotherapy plus radiotherapy failed to improve outcome markedly. Improvement will come from understanding the biology of the disease and integrating new targeted therapies into the treatment of this rare and aggressive tumor.

Breast sarcomas: current and future perspectives.

Breast sarcomas are rare neoplasms of the breast that need to be clearly distinguished from the very common breast carcinomas and treated in a multidisciplinary manner modelled after treatment paradigms in other sarcoma locations. An increasing need to differentiate sarcoma sub-types based on molecular characteristics that will also be depicted in differential treatment sensitivities and development of specifically targeted therapies are equally valid in sarcomas in general and in breast sarcomas in particular. Of special interest in breast are sarcomas developing after breast irradiation for a previous breast carcinoma, a scenario that is increasingly common, given the increasing trends of breast conservation in the surgical treatment of breast carcinoma that necessitates the adjuvant use of radiotherapy.

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.

Immunotherapy of melanoma is aimed to mobilize cytolytic CD8+ T cells playing a central role in protective immunity. Despite numerous clinical vaccine trials, only few patients exhibited strong antigen-specific T-cell activation, stressing the need to improve vaccine strategies. For a rational development, we propose to focus on molecularly defined vaccine components, and evaluate their immunogenicity with highly reproducible and standardized methods for ex vivo immune monitoring. Careful immunogenicity comparison of vaccine formulations in phase I/II studies allow to select optimized vaccines for subsequent clinical efficacy testing in large scale phase III trials.

Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975.

BACKGROUND: To update the pattern of cancer mortality in Europe. Materials and methods: We analysed cancer mortality in 34 European countries during 2000-2004, with an overview of trends in 1975-2004 using data from the World Health Organization. RESULTS: From 1990-1994 to 2000-2004, overall cancer mortality in the European Union declined from 185.2 to 168.0/100 000 (world standard, -9%) in men and from 104.8 to 96.9 (-8%) in women, with larger falls in middle age. Total cancer mortality trends were favourable, though to a variable degree, in all major European countries, including Russia, but not in Romania. The major determinants of these favourable trends were the decline of lung (-16%) and other tobacco-related cancers in men, together with the persistent falls in gastric cancer, and the recent appreciable falls in colorectal cancer. In women, relevant contributions came from the persistent decline in cervical cancer and the recent falls in breast cancer mortality, particularly in northern and western Europe. Favourable trends were also observed for testicular cancer, Hodgkin lymphomas, leukaemias, and other neoplasms amenable to treatment, though the reductions were still appreciably smaller in eastern Europe. CONCLUSION: This updated analysis of cancer mortality in Europe showed a persistent favourable trend over the last years.