Papers by Dario Giuffrida
Annali italiani di chirurgia
Conservative surgery of thyroid is followed by recurrence in 2 to 70% of cases in an 8-20 years p... more Conservative surgery of thyroid is followed by recurrence in 2 to 70% of cases in an 8-20 years period. The surgical treatment of such recurrence is affected by higher morbidity than a primary total thyroidectomy. We wanted verify in our series this difference and discuss motivations for conservative or radical surgery of goiter. We compared a series of 91 primary total thyroidectomy (A) with 11 cases of total thyroidectomy for recurrence (B) performed between 2001 and 2005. Postoperative complications were: Transient hypocalcemia 7 (7.69%) in A and 3 (27%) in B, Permanent hypocalcemia only 1 (9%) in B, Transient RLN deficit 2 (2.1%) in A and 2 (18.1%) in B. Due to the need of a lifelong therapy with LT4 no utility is observed in conservative surgery of thyroid. Further, in primary surgery, differences in incidence of perioperative complications cannot be advocated to justify a conservative approach. Sophisticated technologies are not able to prevent all damages to parathyroid or to...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 1998
Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, accounting for 5% to 10% of ... more Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, accounting for 5% to 10% of all thyroid malignancies. Approximately 75% of cases are sporadic. Significant advances have been made in the molecular biology of MTC, but some aspects of diagnosis and management still remain controversial. We reviewed relevant articles published in major English-language medical journals. We used the MEDLINE database, selected bibliographies, and articles available in our personal files. Mutations of the RET proto-oncogene have been identified in the germline DNA of patients with familial MTC syndromes. Genetic testing can identify patients affected by multiple endocrine neoplasia types IIA and IIB and familial MTC, allowing early diagnosis and possible cure. Surgical treatment is total thyroidectomy. Plasma calcitonin measurements are excellent markers for postoperative follow-up. Adjunctive therapy includes radiotherapy and chemotherapy. The overall prognosis is worse than papillary...
Journal of Endocrinological Investigation, 2012
Background: The few epidemiological data available in literature on neuroendocrine tumors (NET) a... more Background: The few epidemiological data available in literature on neuroendocrine tumors (NET) are mainly based on Registry databases, missing therefore details on their clinical and natural history. Aim: To investigate epidemiology, clinical presentation, and natural history of NET. Design and setting: A large national retrospective survey was conducted in 13 Italian referral centers. Among 1203 NET, 820 originating in the thorax (T-NET), in the gastro-enteropancreatic tract (GEP-NET) or metastatic NET of unknown primary origin (U-NET) were enrolled in the study. Results: 93% had a sporadic and 7% a multiple endocrine neoplasia type 1 (MEN1)-associated tumor; 63% were GEP-NET, 33% T-NET, 4% U-NET. Pancreas and lung were the commonest primary sites. Poorly differentiated carcinomas were <10%, all sporadic. The incidence of NET had a linear increase from 1990 to 2007 in all the centers. The mean age at diagnosis was 60.0±16.4 yr, significantly anticipated in MEN1 patients (47.7±16.5 yr). Association with cigarette smoking and other non-NET cancer were more prevalent than in the general Italian population. The first symptoms of the disease were related to tumor burden in 46%, endocrine syndrome in 23%, while the diagnosis was fortuity in 29%. Insulin (37%) and serotonin (35%) were the most common hormonal hypersecretions. An advanced tumor stage was found in 42%, more frequently in the gut and thymus. No differences in the overall survival was observed between T-NET and GEP-NET and between sporadic and MEN1-associated tumors at 10 yr from diagnosis, while survival probability was dramatically reduced in U-NET. Conclusions: The data obtained from this study furnish relevant information on epidemiology, natural history, and clinico-pathological features of NET, not available from the few published Register studies. (J. Endocrinol. Invest. 35: 817-823, 2012) © 2012, Editrice Kurtis A.F. an P.F. share first authorship as they have equally contributed to the manuscript.
The Journal of Clinical Endocrinology & Metabolism, 2007
Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer charact... more Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC.
Journal of Clinical Endocrinology & Metabolism, 1997
Endocrine Related Cancer, 2001
Background: Clinically evident cardiac metastases from malignant neoplasms are uncommon. The freq... more Background: Clinically evident cardiac metastases from malignant neoplasms are uncommon. The frequency of thyroid metastasis to the heart is very low. To our knowledge, over the last 20 years only a few cases have been reported in the entire literature. Metastatic cardiac involvement occurs most often during the terminal stage. Patients: We present three cases of anaplastic thyroid cancer with metastatic involvement of the heart. Results: Two of the patients died from cardiac problems. The absence of early symptoms makes the clinical diagnosis of metastatic carcinoma difficult. Conclusions: Anaplastic thyroid cancer is an aggressive cancer with a dismal prognosis. It should be borne in mind as a source of cardiac metastasis and a cause of cardiac death.
The American Journal of Medicine, 1995
Some aspects of thyroid nodule evaluation and management remain controversial. Radionuclide scann... more Some aspects of thyroid nodule evaluation and management remain controversial. Radionuclide scanning provides functional information about nodules and differentiates cold from hot nodules. Although thyroid cancers are cold on scan, most cold nodules are benign. Ultrasonography visualizes the thyroid gland and nodules with remarkable clarity and provides structural information about location, number, size, and consistency of nodules. Widespread application of ultrasonography has resulted in the frequent discovery of incidental (occult) nodules in the general population. The clinical significance of these nodules remains unknown, and their management has created a dilemma for physicians. Current cost-effective evaluation of nodules does not include scanning or ultrasonography as routine frontline tests. In most centers, fine-needle aspiration biopsy has supplanted imaging studies as the routine initial procedure for differentiating benign from malignant nodules. Cytologic diagnosis is reliable and inexpensive, and it results in a better selection of patients for surgery. Limitations include false-negative diagnoses, nondiagnostic results, and indeterminate &quot;suspicious&quot; results. Laboratory test results are usually normal, but determination of serum thyrotropin may identify a hot nodule, and plasma calcitonin may help diagnose medullary thyroid carcinoma. Treatment of thyroid nodules is controversial. In some practices, benign colloid nodules are treated with suppressive doses of levothyroxine. Recent reports cast doubt on the efficacy of this approach, and it is no longer acceptable to select patients for surgical treatment on the basis of suppressive therapy. Furthermore, suppressive levothyroxine therapy may be associated with significant bone and cardiac side effects, especially in elderly patients and postmenopausal women. Our approach is observation for most patients, and we suggest a careful risk-benefit analysis when suppression is considered. Hot (autonomous) nodules can be treated with radioiodine, surgery, or ethanol injection. The use of sensitive thyrotropin assays has revealed that the &quot;euthyroid&quot; hot nodule is often associated with subclinical hyperthyroidism, warranting treatment if risks of osteoporosis are significant. Small (&lt; 1.5 cm) occult nodules can be observed. Larger (&gt; 1.5 cm) nodules can be selectively evaluated by ultrasonographically guided fine-needle aspiration. It is prudent to consider cost of care, risk-benefit analysis, and the low incidence of malignancy in thyroid nodules when diagnostic tests are selected and the treatment plan is outlined.
La Clinica terapeutica
Anaplastic thyroid carcinoma (ATC), accounting for 5% to 15% of primary malignant thyroid neoplas... more Anaplastic thyroid carcinoma (ATC), accounting for 5% to 15% of primary malignant thyroid neoplasm, is one of the most aggressive solid tumors in humans. It is rapidly fatal, with a mean survival of 6 months after diagnosis. Multimodality treatment with surgery and/or external beam radiotherapy and chemotherapy are of fundamental importance for local control of disease and to enhance survival. Molecular biology studies have shown that ATC is associated with a p 53 mutation. ATC usually does not concentrate radioiodine or express thyroglobulin. It is essential to verify the diagnosis histologically because insular thyroid cancer, lymphomas, and medullary thyroid cancer are occasionally confused with undifferentiated neoplasms. Immunohistochemical study is helpful in establishing the diagnosis. Multimodal therapy and development of effective systemic chemotherapy agents would provide to result in improvements in survival although no single agent has yet been identified. Aggressive multimodality treatment regimens show promise in improving local control in patients with ATC. Survival rates however remain low. Despite intense applications of such integrated therapy, no standardized successful treatment protocol has yet been established.
Annals of Oncology
Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histological examination of a tumo... more Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histological examination of a tumor showed the characteristic of epithelial carcinoma and mesenchymal differentiation. We retrospectively analyzed the course of the patient and reviewed the literature in which only 19 other cases are described. Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. Survival is very short despite aggressive multimodal treatment.
European Journal of Cancer Supplements, 2007
European Journal of Cancer Supplements, 2009
Journal of Oncology, 2012
Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH sup... more Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment.
Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasibl... more Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasible, and malignant tissue ablation by 131I administration. This procedure requires levothyroxine withdrawal to obtain high levels of endogenous thyrotropin (TSH) to stimulate radioactive iodine uptake by the malignant tissue. Levothyroxine withdrawal may cause severe adverse effects and complications in patients with concomitant illness or advanced metastatic disease. The recent availability of recombinant human thyrotropin (rhTSH) allows diagnostic whole-body scan (WBS) and thyroglobulin testing without levothyroxine withdrawal. We describe six patients with metastatic differentiated thyroid cancer (DTC) and concomitant illness in whom the use of rhTSH was effective in preventing the complications that patients had previously experienced during hypothyroidism consequent to levothyroxine withdrawal. Our results indicate that rhTSH can be particularly advantageous to avoid signs and symptoms of hypothyroidism and complications because of associated diseases in view of 131I treatment of DTC metastases in selected cases in which levothyroxine withdrawal may be dangerous. Its efficacy to treat advanced metastatic disease should be further investigated.
Diagnostic Pathology, 2013
Surgery, 2001
Anaplastic thyroid carcinoma (ATC) is among the most aggressive of human malignancies. However, t... more Anaplastic thyroid carcinoma (ATC) is among the most aggressive of human malignancies. However, there have been few large studies of histologically well-defined ATC. We report the results of a 50-year experience of this lethal malignancy. We reviewed all cases of ATC managed in this institution between 1949 and 1999. One pathologist (J.R.G.) reviewed all pathologic material. Clinical details were obtained from medical records, and current status of all patients was determined. There were 134 cases, with a female-to-male ratio of 1.5:1 and a mean age of 67 years. Benign thyroid disease was present in 27 cases (20%) and well-differentiated thyroid carcinoma in 31 (23%). Sixty-two patients (46%) had distant metastases at diagnosis, and 98% of the tumors were locally invasive. Primary treatment was surgical for 96 patients (72%). Complete resection was achieved in 29 cases (30%), with &quot;minimal residual disease&quot; in 25. Neither extent of operation nor completeness of resection affected survival (P &gt; .4). Postoperative radiotherapy gave slightly longer median survival (5 vs 3 months), which was not significant (P &lt; .08). Multimodal therapy, including operation, chemotherapy, and radiotherapy, did not improve survival. The outlook for patients with ATC remains grim. Novel treatments for ATC are desperately needed.
Oncology, 2005
was achieved in 4 patients. No surgery-related mortality or signifi cant morbidity was reported. ... more was achieved in 4 patients. No surgery-related mortality or signifi cant morbidity was reported. Adjuvant radiotherapy was delivered in 15 patients, and 30 patients received defi nitive radiotherapy. Conclusion: In the present study, the combination of paclitaxel, carboplatin and gemcitabine has been a safe and active regimen in poorprognosis stage IIIA N2 bulky NSCLC.
Lung Cancer, 2005
The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-tr... more The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease. Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment. Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity. The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy.
Lung Cancer, 2006
Lung cancer is the leading cause of tumour-related deaths in the elderly population but the optim... more Lung cancer is the leading cause of tumour-related deaths in the elderly population but the optimal management of advanced NSCLC in older patients has not been defined to date. The present phase II study was planned to evaluate the efficacy and toxicity of the combination of carboplatin and paclitaxel in elderly patients with advanced NSCLC. Patients (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;70 years old) who had pathologically been proven to have a NSCLC and measurable lesions were treated with paclitaxel (175 mg/m2 for 3h) and carboplatin [area under the concentration-time curve (AUC=5)] on day 1 every 3 weeks. Forty patients were enrolled into the study. The median age was 74 years (range, 70-78 years). Approximately 85% of the patients had stage IV and 80% had a performance status (PS) of 0-1. Nine of the 40 (22.5%; 90% CI 17.6-28.1) included patients had a partial response; one patient (2.5%; 90% CI 1.7-3.2) achieved a complete response. The overall response rate was 25% (90% CI 15.3-38.6). In addition stable disease was observed in 13 patients (32.5%; 90% CI 24.3-40.7). The median survival was 7.8 months (95% confidence interval, 5.1-11.8 months). The actual 1-year survival was 18% (95% confidence interval, 12-29%). The median time to disease progression was 4.1 months (95% CI 2.8-8.5). Overall, 37.5% of patients experienced grade 3-4 neutropenia of any duration with only two patients (5%) developing neutropenic fever. Grade 3 or 4 non-haematological toxicity was uncommon apart alopecia. In the present phase II study the combination of paclitaxel and carboplatin has demonstrated to be active and safe in an age-selected population.
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Papers by Dario Giuffrida