The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma.

BACKGROUND: BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment. METHODS: Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome. RESULTS: The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients. DISCUSSION: In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).

Clinical outcome of low-risk differentiated thyroid cancer patients after radioiodine remnant ablation and recombinant human thyroid-stimulating hormone preparation.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved in Europe as a preparation tool for radioiodine ablation of post-surgical thyroid remnants in patients with low-risk differentiated thyroid cancer (DTC). Published studies report that, both thyroid hormone withdrawal and rhTSH preparation result in similar rates of successful remnant ablation, but few studies have determined the effectiveness of rhTSH preparation on disease recurrence. We sought to determine the clinical outcome, considering both ablation success and disease recurrence, of low-risk DTC patients who underwent (131)I ablation. MATERIALS AND METHODS: This retrospective study describes the clinical outcome of 100 patients treated with (131)I remnant ablation after preparation with rhTSH. After ablation, patients were classified as in complete remission, as having no evidence of persistent disease, or as having clinical recurrence on the basis of a subsequent diagnostic whole body scan with (131)I, stimulated thyroglobulin and cross-sectional imaging studies. RESULTS: Overall assessment of ablation success was verified and obtained in 75% of patients (75/100). Considering only patients who underwent a diagnostic whole body scan and stimulated thyroglobulin without interfering anti-thyroglobulin antibody, complete ablation was obtained in 96% of patients (75/78). After a follow-up of about 4 years, 78 patients are in complete remission: 75 with initial ablation success and three who achieved a complete remission during subsequent follow-up. Among the remaining 22 patients, 21 have no clinical evidence of disease (NCED), indicating the inability to verify the complete remission or to detect residual disease, as in patients with positive thyroglobulin antibody, whereas one has persistent disease demonstrated only by stimulated thyroglobulin. No recurrences were observed. Of four patients initially classified as having persistent disease, one obtained a complete remission and two are now considered NCED. CONCLUSION: Our data confirm the favourable outcome, with low rates of recurrence and persistent disease, of patients with low-risk DTC who underwent (131)I ablation after rhTSH. Moreover, our results compare favourably with those reported in the literature in patients prepared with rhTSH, but also in patients prepared with hormone withdrawal.

The role of external beam radiotherapy in the management of differentiated thyroid cancer.

Well differentiated thyroid cancers (DTC), usually having an indolent course, are generally treated by surgery, i.e., total or near total thyroidectomy, followed by radioiodine and TSH suppressive therapy with thyroid hormone. The beneficial effect of external beam radiotherapy (EBRT) in the treatment of selected metastatic sites (i.e., brain and bone) or for palliation in cases of locally advanced inoperable disease is widely accepted. In contrast, its efficacy in improving postoperative locoregional disease control is still controversial. A better definition of subgroups of patients at high risk of local failure is mandatory. At present, patients older than 40-45 years affected by papillary cancers with macro- or microscopic postoperative residual disease and with extensive extrathyroid invasion appear to benefit from EBRT performed in addition to surgery and radioiodine. The role of EBRT in patients with radioiodine non-responsive progressive disease will also be discussed.

Quality of life in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative irradiation.

AIM OF THE STUDY: To evaluate the quality of life (QL) in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative irradiation. MATERIAL AND METHODS: A self-completed questionnaire covering many disease-, symptom-, and treatment-specific issues was administered to 106 conservatively treated patients affected by non-infiltrating breast cancer. The questionnaire was based on a series of 34 items assessing five main fields of post-treatment adjustment: physical well being, sexual adaptation, aesthetic outcome, emotional/psychological well being, relational behaviour. Furthermore, the patients were requested to evaluate the degree of information provided by the medical staff concerning surgical procedures and radiation therapy, and to evaluate the effects of the treatment on their social and overall life. RESULTS: The questionnaire was completed by 83 patients (78%), who had a median follow-up of 54.5 months. This final sample had a median age of 50 years (range 29-88) at the time of treatment and 54 years (range 32-94) at the time of study. The patients claimed to be in good physical condition. Data relating to sexual life were provided by 93% of the sample. Some limitations in sexuality, some interference with sexual desire, and some modifications during intercourse were reported by 5, 6, and 5 patients, respectively. The subjective evaluations of the cosmetic results of the therapies were generally good. Only 13 patients (16%) reported the perception of a worsened body image. Forty-six percent of the sample (38 patients) declared that they felt tense, 48% (39 patients) nervous, 29% (38 patients) lonely, 59% (41 patients) anxious, and 41% (34 patients) depressed. Only seven patients (8%) declared that the treatment had had a bad effect on their social life, and 15 (18%) thought that their current life had been affected by the treatment. The amount of information received concerning the disease and treatment (surgery and radiotherapy) was considered sufficient by 79%, 75%, and 79% of the sample, respectively. CONCLUSIONS: This study revealed a good QL in patients treated with breast conservation and postoperative irradiation, with a preserved favourable body image and a lack of negative impact on sexuality. Radiation therapy did not lead to any significant additional problems capable of affecting the QL.

[Analysis of recurrences following conservative treatment of breast carcinoma]. / Analisi delle recidive dopo trattamento conservativo del carcinoma mammario.

In the conservative treatment of early breast cancer, great attention must be paid to define the prognostic factors correlated with the local recurrence rate. The goal is to customize surgery, radiotherapy and chemotherapy to the risk predicted in every single patient. To investigate the impact of some prognostic factors in a group of patients treated with homogeneous treatment schedules, 251 women with UICC stage I or II breast cancer were examined in the Padua Radiotherapy Department from 1988 to 1990. All patients underwent conservative surgery consisting in quadrantectomy, axillary node dissection and radiotherapy. During a median follow-up period of 49.2 months, 12 patients presented a breast relapse (4.8%). In 4 patients the relapse occurred in the same quandrant as the primary lesion, whereas a different quadrant was involved in the other 8 patients. The relapse rate in women under 60 was 5% and 4.7% in older patients, with p = 0.73. In pT1 patients, the relapse rate was 4.5% and in pT2 patients it was 7.9% (p = 0.37). No significant difference was observed between pN- and pN+ patients (4.5% vs. 6.25%, p = 0.37). In our series, none of the studied factors significantly influenced breast relapse rates. The number of patients may be too little relative to the low rate of relapses. However, an unfavorable trend was observed in the patients under 60, in pT2 or pN+ patients, or in the patients with positive or unknown surgical margins.

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

Androblastoma de ovario; aspectos clinico-patologicos presentacion de un caso / Clinicopathologycal aspects of a case of androblastoms of ovary

Presentamos un caso de androblastoma, en una paciente de 52 anos de edad, que acudio con un cuadro clinico de amenorrea y signos de virilizacion. El objetivo de este reporte es mostrar un caso de neoplasia rara entre los tumores ovaricos y analizar las caracteristicas clinicas y patologias.

[Neoplasms of the gallbladder and the extrahepatic bile ducts: radio-chemotherapeutic combined treatment. Results in 18 treated cases]. / Neoplasie della colecisti e delle vie biliari extraepatiche: trattamento integrato radio-chemioterapico. Risultati in 18 casi trattati.

According to current literature, the main cause of death in patients with gallbladder (GB) and extrahepatic biliary ducts (EHBD) neoplasms is related to local and locoregional tumor spread rather than to distant metastases. Surgery, even when radical, is followed by a high number of relapses. That is why postoperative radiation therapy (RT) is usually combined with surgery. Alone, however, RT is not effective enough to markedly improve loco-regional control, considering that the adjacent organs would be damaged by higher doses. Referring to experimental studies published in the 1960s and relative to the biological effect of ionizing radiation with 5-Fluorouracil (5-FU) in slowing the pace of tumor growth, the Department of Radiotherapy, together with the Department of Medical Oncology in Padua General Hospital, began administering a combined surgical-chemo-radiotherapeutic protocol in January 1982, to January 1989. The protocol included 5-FU administration both 3 days before and during RT, after a surgical intervention as radical as possible. Eighteen patients were given this treatment. By the end of December 1989, 7 patients were alive--6 of them disease-free with a 26-month mean survival. Eleven patients died--7 due to local/loco-regional relapse, 1 from a distant metastasis, 1 from gastric hemorrhage, with no disease, and 2 from unknown causes. Overall mean survival in the two groups was 16 months. The combined treatment proved to be tolerable and feasible, even though severe complications were observed in 2 patients, 1 case of toxic death (gastric hemorrhage) and another with complete duodenal stenosis which required further surgery.(ABSTRACT TRUNCATED AT 250 WORDS)