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Background: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent., Methods: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears., Results: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts., Conclusions: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

Background: Solitary adrenal metastases (AM) are rare and their management unclear. Surgery, especially laparoscopic adrenalectomy (LA), is debatable in the management of AM. This retrospective study analysed the feasibility and the results of LA for AM., Methods: From 1997 to 2003, 16 patients underwent LA for isolated AM. Completeness of resection, postoperative morbidity and follow-up (FU) were recorded., Results: There were 10 synchronous AM and 6 metachronous AM. Primary tumours included lung cancer (n = 9), melanoma (n = 3), mesothelioma (n = 1), rhabdomyosarcoma (n = 1), colonic adenocarcinoma (n = 1) and renal cell carcinoma (n = 1). Five patients required conversion to an open procedure. Minor complications occurred in three patients. Pathology confirmed the diagnosis of AM. Mean tumour size was 60 (range: 15-110) mm. Nine patients (56%) had complete resections, 3 had positive margins and 4 had incomplete macroscopic resections. Mean observed FU was 25 (range: 1-68) months. Median overall calculated survival was 23 months. Overall 5-year survival was 33% (Kaplan-Meyer). At the end of study, 8 patients were alive with a mean FU of 35 months (3 without evidence of disease). No patient presented with local relapse or port-site metastasis. We did not identify any predictive factors. All patients with incomplete macroscopic resection died within 24 months., Conclusions: LA can achieve an acceptable 5-year survival, comparable to open surgery but with better postoperative comfort. It should be considered for AM with the intention of complete resection. It offers the patient the possibility of tumour resection with the benefit of a laparoscopic approach.

Introduction: Endoscopic thyroid surgery has been shown to be feasible. Most minimal access procedures have been performed via a midline approach. Based on our experience of more than 500 endoscopic parathyroidectomies via a lateral approach we have used the same method for thyroid lobectomy., Methods: We present our experience of endoscopic thyroid lobectomy via a lateral approach (ETLA) and review of the results over a 1-year period (2004). Inclusion criteria for ETLA were (1) solitary nodule with atypical/suspicious fine-needle biopsy (FNB) or solitary toxic nodule; (2) lesions with a diameter of < 3 cm. Patients with a history of previous neck surgery or radiation exposure were excluded. All patients underwent postoperative vocal cord checks and plasma calcium evaluation., Results: A total of 742 thyroid procedures were performed during 2004. Among them, 38 patients (5.1%) underwent ETLA. Indications for surgery were suspicious FNB results (36 patients) and a toxic nodule (2 patients). Mean nodule size was 19.2 mm. Mean +/- SD operating time was 102 +/- 27 minutes. All recurrent laryngeal nerves were identified (including one that was nonrecurrent). Of the 38 patients, the superior parathyroid gland was identified in 36 and the inferior parathyroid gland in 33. There were two conversions due to difficulty with the dissection. Two operations were converted because malignancy was diagnosed on frozen section examination. Two patients underwent a delayed completion thyroidectomy when definitive histology necessitated it. There were no permanent operative complications, and all patients were discharged on the first postoperative day., Conclusions: ETLA offers excellent intraoperative visualization of the vital structures and is a safe alternative to conventional thyroid lobectomy in selected cases.

Because of the rarity of adrenocortical carcinoma, survival rates and the prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors over an 18-year period. A trend study was associated to assess changes in the clinical and biochemical presentations as well as the surgical evolution. A total of 253 patients (158 women, 95 men) with a mean age of 47 years were included. Cushing syndrome was the main clinical presentation (30%), and hormonal studies revealed secreting tumors in 66% of the cases. Altogether, 72% (n = 182) of patients underwent resection for cure, and 41.5% (n = 105) of them had an extensive resection because of metastatic cancer. A lymphadenectomy was performed in 32.5% (n = 89) of the cases. The operative mortality was 5.5% (n = 14). Patients were given mitotane as adjuvant therapy in 53.8% of the cases (n = 135). The results of staging were stage I in 16 patients (6.3%), stage II (local disease) in 126 patients (49.8%), stage III (locoregional disease) in 57 patients (22.5%), and stage IV (metastases) in 54 patients (21.3%). Neither tumor staging nor the rate of curative surgery changed during the study period. More subcostal incisions were performed, and the use of mitotane increased significantly. The 5-year actuarial survival rates were 38% overall, 50% in the curative group, 66% for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV. Multivariate analysis showed that mitotane benefited only the group of patients not operated on for cure. A better prognosis was found in patients operated on after 1988 (p = 0.04), in those with precursor-secreting tumors (p = 0.005), and in those at local stages of the disease (p = 0.0003). Thus mitotane benefited only patients not operated on for cure. Curative resection, precursor secretion, recent diagnosis, and local stage were favorably associated with survival.

Laparoscopic adrenalectomy (LA) has become the gold standard for adrenalectomy. Review of the literature indicates that the rate of intra- and postoperative complications is not negligible. The aim of this study was to evaluate the complications observed in a series of 169 consecutive LAs performed at a same center for a variety of endocrine disorders. Between June 1994 and December 1998 a series of 169 LAs were performed in 159 patients: 149 unilateral LAs and 10 bilateral LAs. There were 98 women and 61 men with a mean age of 49. 7 years (range 22-76 years). There were patients with 61 Conn syndrome, 41 with Cushing syndrome, 1 androgen-producing tumor, 29 pheochromocytomas, and 37 nonfunctioning tumors. Mean tumor size was 32 mm (range 7-110 mm). LA was performed by a transperitoneal flank approach in the lateral decubitus position. Mean operating time was 129 minutes (range 48-300 minutes) for unilateral LA and 228 minutes (range 175-275 minutes) for bilateral LA. There was no mortality. Twelve patients had a significant complication (7.5%): three peritoneal hematomas requiring (in two cases) laparotomy and (in one case) transfusion; one parietal hematoma; three intraoperative bleeding episodes without need for transfusion; one partial infarction of the spleen; one pneumothorax; one capsular effraction of the tumor; and two deep venous thromboses. Eight tumors were malignant at final histology (4.7%), of which four were completely removed laparoscopically. Conversion to open surgery was required in eight cases (5%): for malignancy in four cases, difficulty of dissection in three cases, and pneumothorax in one case. With a mean follow-up of 26.58 months (range 6-60 months) all patients are disease-free. We conclude that LA is a safe procedure. With increasing experience the morbidity becomes minor. To avoid complications LA should be converted to open surgery if local invasion is suspected or if there is difficulty with the dissection.

Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical stage often associated with lymph node involvement. Hence surgical treatment does not result in definitive cure in many patients. Studies have demonstrated that routine measurement of serum basal calcitonin (CT) in patients with nodular thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim of this work was to assess the results of surgery in patients operated on for subclinical SMTC detected preoperatively by measurement of serum CT. Results were compared with those obtained in patients with SMTCs diagnosed at a clinical stage and operated on during the same period. During a 4-year period (1993-1996) 24 SMTCs were diagnosed and treated in our department. They were diagnosed at a clinical stage in 13 patients (group 1): palpable thyroid tumor (n = 11), palpable metastatic lymph node (n = 6), distant metastases (n = 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery.

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.

We have previously demonstrated that in 95.6% of malignant thyroid tumors the enzyme thyroid peroxidase (TPO) presents antigenic changes detectable by a monoclonal antibody termed MoAb47. The aim of this study was to investigate the interest of TPO immunodetection for the diagnosis of malignancy on fine-needle aspiration biopsy (FNAB) of thyroid nodules. The study was performed on 300 patients. Slides of FNAB aspirate were air-dried and stained by anti-TPO-MoAb47. According to the percentage of TPO-positive epithelial cells, patients were divided into two groups: benign (> 80%) and malignant (< 80%). In 279 cases additional slides were available for Giemsa stain and standard cytology. All the patients were operated on, and the final diagnosis was recorded as benign in 248 cases (183 macrofollicular nodules, 23 microfollicular adenomas, 18 atypical adenomas, 11 oncocytomas, 11 thyroiditis, 2 Graves' disease) and malignant in 52 cases (44 papillary carcinomas and 8 follicular carcinomas). Samples from 215 of 248 benign nodules yielded 80% to 100% TPO-positive cells, whereas samples from all malignant tumors yielded less than 80% positive cells. The sensitivity of TPO staining for diagnosis of malignancy was thus 100%, its specificity 86.7%, and its overall accuracy 89%. With conventional cytology, sensitivity, specificity, and accuracy were 91.6%, 79.2%, and 81.0%, respectively. We conclude from this study that TPO staining with MoAb47 should become an essential adjunct in the preoperative cytologic diagnosis of thyroid nodules.

An immunohistochemical study using two monoclonal antibodies (MoAb 30 and MoAb 47) against thyroid peroxidase (TPO) was performed on surgical specimens of human thyroid carcinoma (n = 65), adenoma (n = 70) and Graves' disease (n = 10). Normal adjacent thyroid tissue was used as positive control. Monoclonal antibody 30 reacted significantly with all adenoma and most carcinoma, whereas MoAb 47 reacted with 66 adenoma but only two carcinoma. Of the four adenomas that did not react with MoAb 47, three were of the fetal type. Both carcinoma reacting with MoAb 47 were of the well-differentiated follicular type. These findings further confirm the hypothesis that thyroid carcinoma is associated with changes in the quantity and antigenic properties of TPO. Although the alterations in antigenic behavior revealed by MoAb 47 are not 100% specific, they may allow more accurate diagnosis of malignancy in thyroid tumors.

Among 258 patients operated on for secondary hyperparathyroidism (HPT II) from 1971 to 1988, a total of 33 had one or more reoperations for persistent or recurrent HPT II. These reoperations did not induce any mortality or significant morbidity. After inadequate parathyroidectomy (25 cases), 15 patients were reoperated. Twelve of these had undergone initial surgery at another institution. Three patients died of causes unrelated to their HPT II. The other 12 patients are disease-free. After successful subtotal parathyroidectomy (79 cases), 2 patients (2.5%) had a recurrence 5 and 6 years later, respectively. Currently, the 2 patients remain disease-free. After total parathyroidectomy with autotransplantation (152 cases), 16 patients (10.5%) had reoperations on the grafts. The mean time before reoperation was 2 1/2 years. Hypertrophy of grafted fragments was observed in 4 cases (2.6%), but only 2 of these 4 patients were cured by removal of the grafts. Residual parathyroid tissue or a supernumerary gland in the neck or the mediastinum was suspected in 5 patients, but this could not be confirmed because one had already been reoperated on in the neck without success, another still refuses reoperation, and 3 died. In 6 other patients, the recurrence was debatable and HPT II was not confirmed. In the last 3 patients, the diagnosis was incorrect and aluminum intoxication was proved later. Results of reoperations for persistent or recurrent HPT II depend, first, on a correct diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effectiveness of an immunoperoxidase technique using four monoclonal antibodies (mAb) is compared to a technique using one polyclonal antibody (pAb) to detect human thyroglobulin (Tg) in paraffin sections of 55 thyroid carcinomas. With the pAb, a positive reaction was found in 82% of the cases. With the four mAb, the presence of Tg was demonstrated in 96.5% of the cases. The mAb gave better results than the pAb on poorly differentiated and anaplastic thyroid carcinomas. Many of the thyroid carcinomas in this study, especially the poorly differentiated and anaplastic type, failed to react with all four mAb to Tg. These results confirm the notion of the heterogeneity of Tg in thyroid carcinomas and indicate that a battery of carefully selected mAb can be successfully used for routine histopathologic detection of Tg in these tumors.

Lactoferrin has been identified as the factor in human colostrum that accounts for the increased incorporation of thymidine into DNA in a rat crypt enterocyte bioassay. Commercially available infant formulas used in the refeeding of infants who have severe dietary intolerance associated with mucosal atrophy were tested in this bioassay. In contrast to human milk, no stimulation was observed with these formulas in the assay. All formulas inhibited basal thymidine incorporation. The degree of inhibition of the basal assay progressed from 14% with cow's-milk formula to 30% with soy-based formulas to 45% with hydrolyzed casein formulas. When the formulas were supplemented with lactoferrin to match the level of that in human milk, the result was a 35% relative increase in thymidine incorporation into DNA. The quantitative level of response was primarily influenced by the baseline inhibitions associated with the specific formulas. The most profound effect was observed with the hydrolyzed casein formula, when lactoferrin supplementation reversed the baseline inhibition but did not result in a response greater than that seen in control basal bioassays. The supplementation of infant formulas with lactoferrin improved the thymidine incorporation in rat crypt enterocytes; a response equivalent to that of human milk, however, would require a redesign of other formula components to reduce basal inhibition.