Jean-Paul Travagli

Long-term results and prognostic factors in patients with differentiated thyroid carcinoma

A multivariate analysis of the prognostic factors was carried out on a series of 546 differentiated thyroid cancers followed for 8 to 40 years. For survival, the highest risk factor was associated with age; tumors diagnosed in patients younger than 45 years had higher relapse‐free survival (RFS) and total survival (TS) rates and a slower growth rate. In children, although the RFS and TS at 15 years were high, they decreased later. The second independent prognostic factor was histology. There was no difference between papillary and follicular well‐differentiated (FWD) tumors, but follicular moderately differentiated (FMD) had lower TS and RFS. Among FMD cancers, relapses occurred earlier and the interval between relapse and death was shorter. The third factor was sex. Tumors tended to disseminate more in male than in female patients. The survival rate after relapse was the same, however, suggesting that the growth rates are not different. The presence of palpable lymph nodes also had a significant independent impact on both TS and RFS. Patients treated after 1960 have a better outcome than patients treated earlier, although they did not differ in age distribution, histologic characteristics, sex ratio, or incidence of palpable lymph nodes. The distribution of time intervals between treatment and relapse was not compatible with an exponential failure time model but fit with a log‐logistic model. Relapses can occur as late as 30 years or more after initial treatment. Elevated levels of circulating thyroglobulin have been observed in about 12% of the patients who had been in complete remission for longer than 20 years.

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy

Abstract Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and a low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

Malignant pheochromocytoma: Clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases

Twenty patients, 16 males and 4 females, aged 11–76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11,10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuropeptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanilic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant métastase in 10. lodine-131 MIBG therapy was performed in 11, among whom 9 were évaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3–60). Response to therapy was poor and warrants further cooperative trials.

Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inflammatory stroma

The hallmarks of diagnosis of medullary breast cancer (MedBC) used by the authors since 1977 have been that the tumor is well circumscribed, has syncytial architecture in greater than 75% of its surface, contains diffuse inflammatory infiltrate, has atypical nuclei, and forms no glandular pattern. In order to assess the clinical utility of these criteria, we studied a series of 95 previously untreated, surgically operable patients with breast carcinoma at the Institut Gustave‐Roussy (IGR) between 1960 and 1979. A diagnosis of MedBC was initially made for these patients or suspected based on abundant inflammatory stroma observed in a histologic evaluation. Using these criteria, 26 cases were identified as typical medullary carcinoma (TMC), 23 cases as atypical medullary carcinoma (AMC), and 46 cases as nonmedullary carcinoma (NMC). The 26 cases of TMC represent a very small fraction of the total infiltrating operable breast carcinomas diagnosed at IGR during the same time period. The prognosis for these 26 patients was much more favorable than for the other groups. They had a 10‐year disease‐free survival of 92% compared with 53% for the AMC group and 51% for the NMC group. Neither distant metastasis nor secondary primaries of the same histology were seen. Therefore, it is possible with the use of strict histologic criteria to distinguish a group of patients with a much more favorable prognosis. This histologic diagnosis alone renders a most favorable prognosis for the patient even if other factors such as large tumor size and lymph node involvement are present and, by inference, the only therapy needed is the removal of all tumor. In contrast, atypical forms have a prognosis no different from other atypical types of breast carcinomas without inflammatory stroma, and adjuvant therapy appears to be justified if other factors warrant it.

Medullary thyroid carcinoma: Prognostic factors and treatment

Seventy-five patients with medullary thyroid carcinoma (MTC) have been treated at Institut Gustave-Roussy from 1932 to 1979. Of these, 13 patients had distant metastases and received palliative treatment, their median survival was 3 years. Sixty-two patients with MTC limited to the neck received curative treatment; 6 had exclusive external radiotherapy for inoperable disease and 56 were surgically treated: 23 by total thyroidectomy and 33 by partial thyroidectomy. After surgery 29 patients received external radiotherapy for cervical lymph node involvement (25/29) and/or incomplete surgical resection (12/27). The survival rate was 69% at 5 years and 48% at 10 years. It was lower in patients with distant metastases at presentation (p less than 10(-5)), with tumoral infiltration of the posterior tissue planes (p less than 0.025) and in patients in whom surgical excision had not been satisfactory (p less than 0.01). It was not correlated with cervical lymph node involvement probably because those patients with lymph node involvement had been irradiated. The 29 patients who received post-operative cervical radiotherapy had initially more extensive local disease (p less than 0.05) than the 27 patients treated by surgery alone, nevertheless their survival was slightly higher. No difference in survival rate was observed between patients treated by total thyroidectomy or partial thyroidectomy, among whom only 4 local recurrences occurred. Three of the 6 patients treated with external radiotherapy alone experienced long survival (4, 7 and 10 years) and a fourth is still in clinical remission 4 years after treatment. The effectiveness of chemotherapy in patients with metastases was poor, only one patient out of 6 had a partial remission following a treatment by adriamycin. In the familial form and multiple endocrine neoplasia type II, total thyroidectomy appears to be indicated. In the sporadic cases, partial thyroidectomy is usually sufficient. External radiotherapy is effective in MTC and seems to be able to eradicate small foci of residual tumor; it is indicated when surgical excision is impossible or incomplete.

Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course.

Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill‐defined.

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type IIa: Retrospective French Multicentric Study

Abstract. Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) type IIa is rare, occurring in 20% to 30% of the patients. The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d’Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group). This retrospective study was based on cases registered by the GETC (20 participating centers) from 1969 to 1994. Characteristics of PHPT in 56 patients (31 women, 25 men) with MEN-IIa were reviewed. All but two underwent cervicotomy. The median age at diagnosis was 37.6 years. PHPT was found concomitantly with medullary thyroid carcinoma (MTC) or pheochromocytoma in 43 patients (77%). PHPT was asymptomatic in 68% of the patients. Serum calcium levels ranged from 2.20 to 3.70 mmol/L (median 2.82 mmol/L; normal 2.10–2.60 mmol/L). The number of parathyroid glands removed at surgery was 0 (n = 2), 1 (n = 24), 2 (n = 5), > 2 (n = 12), 4 (n = 11). Pathology (initial surgery) consisted of 24 adenomas, 4 double adenomas, and 25 hyperplasia. Cure after initial surgery was obtained in 89%, including a 22% incidence of hypoparathyroidism. There were 6 cases (11%) with persistent PHPT. With a mean follow-up of 6.4 years, five patients (9%) had recurrent PHPT. The results indicate that MEN-IIa-related PHPT is generally associated with mild, often asymptomatic hypercalcemia. Despite recurrences encountered 5 to 15 years after the first cervicotomy, resection of only macroscopically enlarged glands generally appears sufficient. Subtotal or total parathyroidectomy with autotransplantation is associated with a high rate of hypoparathyroidism.

Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer.

SummaryImmunohistochemical (IHC) techniques should allow for a greater detection of bone marrow micrometastasis in patients with breast carcinoma. We studied a series of bone marrow (BM) biopsies negative by conventional histologic techniques from 93 patients with breast carcinoma. Prior to this study, twelve BM biopsies, positive by conventional histology, were stained with a panel of monoclonal antibodies (MoAb), directed either against cytokeratin (KL1, AE1-AE3, CAM5-2) or epithelial membrane antigen (EMA, HMFG2). KL1 appeared to be the most sensitive of the markers used in the detection of metastases and is available commercially. It therefore was the only MoAb used with the series of 93 BM biopsies negative by conventional examination. Within this series, among 45 patients clinically suspected of having bone marrow metastasis but with BM biopsies negative by conventional staining, one case showing myelofibrosis stained positive with KL1 demonstrating isolated tumor cells. For the 48 patients without suspicion of bone marrow metastasis at initial diagnosis for breast carcinoma, KL1 revealed no marrow metastasis.Single bone marrow biopsy techniques whether stained by conventional or IHC methods do not appear to be useful tests to detect occult bone marrow metastasis, especially at initial diagnosis of clinically Mo breast carcinoma patients.

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

Invasive apocrine carcinoma of the breast: a long term follow-up study of 34 cases

We have reviewed the morpho-functional criteria for infiltrating apocrine carcinomas of the breast and analysed long term follow-up of this entity. Thirty-four cases of pure apocrine carcinomas were retrieved from the files of the Dept. of Pathology, IGR, France, for the years 1955–1982. Each case was matched with two controls of other infiltrating ductal carcinomas according to the most important prognostic parameters: nodal status, histograde, anatomic tumor size, and patient age. No significant difference between the survival curves of the two groups was seen. Apocrine carcinoma, although possessing peculiar morphological, ultrastructural, biochemical, and immunohistochemical features to merit recognition as a separate histologic variant of breast cancer, by itself has no apparent clinical significance.