Surgical treatment of anaplastic thyroid carcinoma. Our experience.

BACKGROUND: In anaplastic thyroid carcinoma (ATC) surgical resection associated to radiotherapy and chemotherapy can ameliorate local disease control with occasional long-term survivals. PATIENTS AND METHODS: Resection of the tumor was accomplished in 20 ATC patients, with no macroscopic (13 cases) or minimal residual neck disease infiltrating vital structures (7 cases). Ten of these patients (50%) had distant metastases. Sixteen cases were also treated with radiotherapy and chemotherapy, while in one patient only chemotherapy was possible; 2 patients refused further therapy; the last one is starting adjuvant treatment. Morbidity and survival were analysed, and compared with other 15 ATCs submitted to partial tumor debulking or not operated at all (control group). RESULTS: Function of at least one laryngeal recurrent nerve was preserved in all 20 patients; none experienced permanent hypoparathyroidism. At last follow-up examination 17 patients had died and 3 were alive 1, 6 and 80 months after the operation, the latter being free of disease. Survival of dead patients ranged from 3 to 28 months (mean: 8 months). In the control group all patients died, survival ranging from 1 to 13 months (mean: 4 months). Actuarial analysis of survival showed a significant difference between the two groups (p = 0.0112); multivariate analysis of several prognostic factors confirmed that complete or near complete tumour resection was the most relevant. CONCLUSIONS: Surgical resection is an important component of the multimodal treatment of ATC and should be attempted whenever possible.

Is central neck dissection a safe procedure in the treatment of papillary thyroid cancer? Our experience.

BACKGROUND AND AIMS: The role of central neck dissection in the treatment of papillary thyroid carcinoma is debated. This retrospective investigation was undertaken to assess whether it augments total thyroidectomy morbidity. PATIENTS/METHODS: A total of 305 consecutive patients who had undergone total thyroidectomy for papillary thyroid carcinoma were divided into three groups: group A (n = 64) showed evidence of node metastases and received therapeutic bilateral central node dissection; group B (n = 93) showed negative nodes and received prophylactic ipsilateral central node dissection; group C (n = 148) showed negative nodes and received total thyroidectomy alone. The rates of transient and permanent complications within the three groups were compared. RESULTS: Histopathological examination detected node metastases in 46 (72%) group A patients and in 20 (21%) group B patients. Parathyroid autotransplantation was carried out in 41 (64%) patients in group A, 55 (59%) in group B, and 43 (29%) in group C (P < 0.001). One or more parathyroid glands were found in 20% of the specimens from group A, 11% of those from group B, and 9% of those from group C. None of the patients in either group A or group B reported permanent laryngeal recurrent nerve paralysis, but two (1.3%) in group C did. Transient laryngeal recurrent nerve paralysis occurred most often in group A patients (7.8% versus 5.4% versus 1.3%, respectively) and was bilateral in two patients (one in group A and one in group B). None of the patients in either group A or group B developed permanent hypoparathyroidism, but four (2.7%) in group C did. Transient hypoparathyroidism was highest in group A patients (31% versus 27% versus 13%, respectively; P = 0.003). Postoperative bleeding requiring reoperation occurred in one group B patient and in two group C patients. CONCLUSIONS: Central neck dissection did not increase permanent morbidity and revealed a significant rate of nonclinically evident node metastases. In experienced hands, central neck dissection should be routinely combined with total thyroidectomy in the primary treatment of pre- or intraoperatively diagnosed papillary thyroid cancer. When no macroscopic evidence of metastasis is present, ipsilateral central neck dissection is the best treatment strategy in a balanced decision between the need for achieving local radical excision, correct disease staging, and reducing the risk of complications.

[Surgical treatment of Graves' disease: results in 108 patients]. / Trattamento chirurgico del morbo di basedow: risultati in 108 pazienti.

AIM OF THE STUDY: To evaluate morbidity and functional results of surgical treatment in patients with Graves' disease. METHODS: A retrospective study was performed in 108 patients operated on during 1993-2003. Main indications for surgery were failure of treatment with antithyroid drugs (80.6%), large goiter (46.3%) and/or severe ophthalmopathy (23.1%). Surgical procedures were extensive subtotal thyroidectomy (EST; n = 33; uni- or bilateral remnant of <2 g) or total thyroidectomy (TT; n=75). Functional results were established in 89 patients (27 EST patients and 62 TT patients) after a mean follow-up of 5.9 years. RESULTS: Operative mortality was zero. There were 4 (3.7%) transient unilateral recurrent laryngeal nerve (RLN) palsies and no cases of permanent RLN palsy. Temporary hypocalcemia occurred in 15 patients (13.9%) and permanent hypoparathyroidism resulted in two (1.9%). Four patients (3.7%) developed a postoperative hematoma that required reoperation. There was no significant difference in the rate of complications between EST and TT, although temporary hypocalcemia was more common following TT than EST (17.3% vs. 6.1%) and permanent hypoparathyroidism affected only TT patients. None of the patients developed recurrent hyperthyroidism; all patients are maintained on levothyroxine. CONCLUSIONS: Surgery is an effective therapy for selected cases of Graves' disease. When performed by experienced surgeons, it can be carried out with no mortality and minimal morbidity. EST (with uni- or bilateral remnant of <2 g) and TT are both effective in order to achieve a definitive cure of hyperthyroidism.

[Post-thyroidectomy cervical hematoma]. / L'ematoma cervicale postoperatorio nella chirurgia tiroidea.

AIM: Postoperative hematoma is a complications of thyroid surgery uncommon but potentially life threatening. It has implications for the trend toward outpatient procedures. METHODS: Retrospective review of 1.221 thyroidectomies performed at our institution over a 6-years period, to identify patients with hematomas requiring reoperation. Symptoms, treatment and findings at reoperation were evaluated. A control group (n=120) was compared for perioperative risk factors and outcome. RESULTS: Eighteen patients (1.5%) developed a postoperative hematoma. Symptoms included neck pain/pressure in 10 patients, respiratory distress in 9, wound drainage in 2, dysphagia in 1, agitation and sweating in 1. Mean time to symptom onset was 12 hours (range: 1.3-40 hours). Six hematomas presented between 7 and 24 hours, and 3 beyond 24 hours. Six patients required bedside hematoma evacuation. The bleeding source was identified in 15 patients. All patients recovered well, but one required a temporary tracheostomy. Case/controls comparison yielded in the study group a higher prevalence of hyperthyroidism (55.6% vs 25.8%, P=0.022) and intrathoracic goiter (50% vs 22.5%, P=0.029), and a longer mean hospital stay (5.22 vs 4.1, P=0.012); morbidity was not increased. CONCLUSIONS: Postoperative hematoma is an uncommon complication of thyroid surgery. If treated promptly, serious consequences can be avoided. The relatively long interval between the initial operation and the hematoma development needs to be considered when establishing outpatient practice guidelines.

[Multiple endocrine neoplasia type 2. Biological and clinical aspects]. / Neoplasie endocrine multiple. Aspetti biologici e clinici. Clinica e diagnostica della MEN 2.

CLASSIFICATION: Medullary thyroid carcinoma (MCT), a rare thyroid malignancy originating from the parafollicular C cell, may occur either as a hereditary or a non-hereditary entity. Hereditary MCT can occur either alone, familial MCT (FMCT), or in multiple endocrine neoplasia type 2 (MEN 2), associated with other endocrinopathies such as pheochromocytoma and/or hyperparathyroidism (MEN 2A and 2B). These hereditary disorders are due to germline mutation in the RET proto-oncogene. Early diagnosis and treatment significantly improve the outcome of patients with MCT. DIAGNOSIS: In hereditary MTC, the MTC is usually multifocal and bilateral. Serum calcitonin measurement, a marker of disease, is superior to fine needle aspiration cytology in suggesting the diagnosis of MCT. Other investigations including ultrasonography, chest X-ray, computerized tomography and MRI may provide valuable topographic details in the assessment of the location and size of the primary tumor and metastases. The adrenomedullary disease is usually multicentric and bilateral, often detected after the onset of MCT; this disease is sought by measurement of urinary metanephrines and fractionated catecholamines. The tumor should be localised by computed tomography or MRI scans; 131I-MIBG scintigraphy is used to confirm diagnosis. Primary hyperpathyroidism generally have no symptoms, although hypercalciuria and renal calculi may occur; we screen for this disease by measurement of serum calcium, once hypercalcemia is documented, serum intact PTH should be measured to confirm the diagnosis. High-resolution small part sonography is sometimes used to differentiate parathyroid hyperplasia from solitary adenoma.

[Treatment of familial medullary thyroid carcinoma]. / Il trattamento del carcinoma midollare familiare della tiroide.

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy, which is familial in 25-29% of cases. Familial MTC is due to germ-line mutations in the RET proto-oncogene. It can occur either alone or as the thyroid manifestation of MEN 2 syndromes; the disease is inherited in an autosomal dominant fashion with age-related penetrance. The treatment of choice is surgery. Early diagnosis and an adeguate initial operation provide the best chance of cure. Hence, the diagnosis should be made preoperatively. Genetic testing can identify almost all affected individuals with hereditary disease and permits prophylactic/early thyroidectomy in gene carriers. Total thyroidectomy and lymphadenectomy of the cervicocentral compartment is mandatory in all patients. In addition, bilateral dissection of the cervicolateral compartment should be done in all cases with more than microscopic disease. Plasma calcitonin is an excellent marker for postoperative follow-up. Treatment of persistent/recurrent disease is primarily surgical. Hence, a reoperative cervical lymphadenectomy should be considered in patients with persistently elevated calcitonin levels and no signs of distant metastases. Chemotherapy and external radiotherapy have little impact on the course of avanced disease; more promising is metabolic radiotherapy with Y90-DOTATOC in patients with somatostatin receptor-positive tumours.

[Integration of B-mode and color Doppler ultrasonography in the preoperative diagnosis of thyroid lesions. Preliminary experience in 91 cases]. / Integrazione ecografica B-mode e color-Doppler nella diagnosi preoperatoria di lesioni tiroidee. Esperienza preliminare in 91 casi.

Ninety-one patients affected with thyroid diseases (97 lesions) were examined with conventional B-mode and color-Doppler US. To verify if color-Doppler is able to provide additional elements in the US diagnosis, for each lesion were expressed two diagnosis: the first found on conventional US patterns and the second on color-Doppler patterns. US diagnosis was compared with histologic findings that identify 73 benign lesions and 24 malignant lesions. With conventional B-mode US the diagnosis was correctly expressed in 62/73 benign lesions (85%) and in 18/24 malignant lesions (75%) while it misdiagnosed as positives 11/73 case (15%) and as negatives 6/24 cases (25%). If we completed the conventional US diagnosis with color-Doppler patterns, the false negative reduced to 4% and false positive to 6.8%. On the whole, although any correlation between color-Doppler patterns and different histological types was found, the color-Doppler had a high predictive value of benignity in patterns I, II, and IV while pattern III is not peculiar because it includes either malignant or benign lesions.

Primary hyperparathyroidism sustained by a giant adenoma of the parathyroid gland.

A case of primary hyperparathyroidism sustained by an unusually large parathyroid adenoma is presented. The tumor affected a 45-year-old woman with a 15-year history of nephrolithiasis and presented as a palpable neck mass. On the basis of clinical findings and ultrasound examination, it was initially misdiagnosed as a thyroid nodule. CT scan and transesophageal endosonography gave a correct definition of the tumor, which was located behind the left thyroid lobe and expanded posterior to the pharynx and the esophagus in the prevertebral space. At surgery a parathyroid tumor measuring 8 x 7 x 3 cm and weighing 90 g was successfully removed. No signs of malignancy were observed by both morphological and cell kinetic analyses.

[Acute diverticulitis of the appendix. A clinical case]. / Diverticolite acuta dell'appendice. Caso clinico.

The authors describe a case of acute diverticulitis of the appendix presenting as an inflammatory mass in the right lower quadrant of the abdomen. The histologic and clinical findings are discussed. This uncommon condition may mimic acute appendicitis, but in most instances it departs from typical appendicitis for later age of appearance, more indolent clinical course and increased tendency to perforation. In these cases the disease may progress with subacute interstitial inflammation, with or without abscess formation, and present as a tumor-like mass of the cecum.

Multiple endocrine neoplasia (MEN IIB) with Cushing's syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone.

We describe a case of Cushing's syndrome caused by a medullary thyroid carcinoma (MCT) secreting corticotropin-releasing-hormone (CRH) in a young woman presenting mucosal neuromas located on the top of the tongue and eyelid areas. Laboratory studies showed, basally and after dexamethasone suppression test, serum cortisol and plasma pituitary corticotrophin (ACTH) levels agreed with an ectopic Cushing's syndrome. Immunohistochemical studies of the MCT tissue revealed a production of CRH and scattered cells containing vasopressin but not ACTH peptides. This is the first demonstrated case of a CRH-secreting tumor in multiple endocrine neoplasia (MEN IIB) syndrome.

[Prognostic value of nuclear morphology in colorectal neoplasms]. / Valore prognostico della morfologia nucleare nelle neoplasie del colonretto.

Cytomorphometry measures the main geometric parameters of the cell nucleus (area, min. and max. diameter, circunference) on ordinary histological preparations. It has been employed to asses the prognosis of breast and ovary tumours. The possibility that cytomorphometry, when allied with other parameters, such as age, sex, Duke's stage, bleeding etc., can be used in the prognosis of tumours of the large intestine is examined through a study of intraoperative biopsies from 44 patients followed after surgery. Univariate analysis showed that the Duke's stage and tumour site were significantly related to prognosis. The standard deviation of the maximum diameter and circunference were also related to survival with a negative correlation. Multivariate analysis confirmed the significance of the maximum diameter and the Duke's stage. These parameters were then used to calculate the relative risk. If due account is taken of the reservation expressed in the literature concerning the reproducibility of the data offered by cytomorphometry and its heavy dependence on the skill of the operator, it can be used to advantage in the prognosis of the colorectal tumours.

[Prognostic value of nuclear morphometry in follicular carcinoma of the thyroid gland]. / Valore prognostico della morfometria nucleare nel carcinoma follicolare della tiroide.

Histological material from 60 cases of follicular carcinoma of the thyroid operated between 1962 and 1987 was examined morphometrically to see whether this would produce data that could be correlated with survival. Nuclear parameters (area, perimeter, minimum and maximum diameter and their ratio, form factor) and the mitotic index were investigated. At the same time, account was taken of certain clinical parameters (sex, age, degree of differentiation, size of the primary lesion, extension of the tumour) potentially correlated with prognosis. Survival in relation to all these variables was examined by means of an actuarial method and subjected to both uni- and multivariate analysis. The results, although suggesting the existence of a relationship between nuclear size and the aggressiveness of this type of tumour, failed to demonstrate a significant correlation between these morphometric parameters and survival after treatment. By contrast, survival was significantly influenced by some of the clinical variables, particularly loco-regional extension of the disease and the patient's age. The prognostic significance of nuclear size was recently demonstrated in breast cancer and in a series of thyroid carcinomas including tumours with different morphologies and progression patterns. In follicular thyroid carcinoma the degree of cellular pleomorphism is usually low. So, morphometry does not seem able to provide information regarding prognosis more valuable than those obtained by the clinical data.

[Precedents of benign thyroid pathology in carcinoma of the thyroid]. / Precedenti di patologia tiroidea benigna nel carcinoma della tiroide.

The clinical history of 125 thyroid cancer (99 women and 26 men) operated on between 1985 and 1992 is reviewed. Previous benign thyroid disease is recorded in 52% of all cancers; this was generally goitre or a thyroid nodule, and in few cases hyperthyroidism. Previous disease is observed in 75% of insular, in 68% of follicular, in 51.5% of papillary, in 35% of anaplastic carcinomas. It is supposed that previous thyroid disease is a risk factor in the development of cancer.

[Poorly differentiated "insular" carcinoma of the thyroid: long-term survival]. / Il carcinoma scarsamente differenziato "insulare" della tiroide: sopravvivenza a distanza.

Poorly differentiated "insular" thyroid carcinoma is a rare, aggressive and often lethal variant of thyroid cancer. Thirty-one cases of this entity were encountered over a 18-yr period. In most of them surgical therapy consisted of total or near-total thyroidectomy. Six patients had distant metastases and/or mediastinal or tracheal infiltration at presentation. Fifteen out of 25 apparently cured after surgery (60%) developed recurrence in the neck and/or distant sites. Radioiodine was employed to destroy thyroid remnants (22 cases) and subsequently to treat persistent/recurrent disease (17 cases). Thirteen patients showed radioiodine uptake in neoplastic lesions and in 3 cases complete resolution was observed. After a mean follow-up of 4.5 years (range 1-16) 6 patients had died of their tumor, 12 are alive with persistent/recurrent disease, 13 do not show any evidence of disease. This experience confirms that "insular" carcinoma tends to have an aggressive behavior, but therapy can be effective. Recognition of this entity is therefore important for planning adequate surgical approach and subsequent patient management.

[Parathyroid transplantation and cryopreservation techniques]. / Trapianto di paratiroidi e techniche di crioconservazione.

This report reviews several aspects of parathyroid transplantation, including some technical aspects of cryopreservation. The problems concerning the control of autograft are also presented, with a little review of the more recent references. These results lead to the recommendation that total parathyroidectomy and autotransplantation should be considered as the method of choice in the treatment of secondary hyperparathyroidism.

Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns.

Poorly differentiated carcinomas of the thyroid share insular, trabecular, and solid histological patterns that are different from those of papillary, follicular, medullary, and anaplastic varieties. We have collected 63 cases of poorly differentiated thyroid carcinomas. Thirty-one tumors (Group A) corresponded to the so-called insular carcinomas, and 32 tumors (Group B) had predominant trabecular and solid or focally follicular patterns in the presence of a minor insular component. The cells characterizing these lesions were relatively small and globoid, with uniform nuclei and intracytoplasmic deposits of thyroglobulin. They were in every respect similar to primordial cells present in the early stages of fetal thyroid development. None of the tumors proved fatal within 6 months, and most responded to radioiodine therapy. Although no differences in survival between the two groups were found, a significantly (p < 0.01) higher percentage of recurrences or distant metastases was observed with Group A tumors. The term primordial cell carcinoma appears appropriate for this type of tumor, which displays characteristic histocytological features and production of thyroglobulin. Clinically, these tumors are aggressive but generally show a slow course and good response to radioiodine therapy.

[Ischemic colitis manifested as Crohn's disease. A case report]. / Colite ischemica manifestatasi quale morbo di Crohn. Case report.

Ischaemic colitis has many and different clinical features as it is often linked to the severity of ischaemic injury. In this paper two patients with clinical features of Crohn's disease are reported. In both patients the diagnosis has been confirmed with endoscopy and biopsy. They have been treated with specific therapy until they developed bowel obstruction in one case and peritonitis in the other. Both patients underwent laparotomy and the histological specimen showed a picture of ischaemic colitis. In one case a Dixon's resection was done, in the other Hartmann's operation.

[Diagnostic approach to extra-renal pheochromocytoma]. / Approccio diagnostico ai feocromocitomi extra-surrenalici.

Stress is laid on certain principles of diagnostic research in the event of extra-suprarenal pheochromocytomas. The importance of CT is recalled, specifying the usefulness of complementary examinations such as selective venous catheterism and above all of scintigraphy with 131I MIBG.

[Blood cholesterol in patients with cancer]. / La colesterolemia nei soggetti affetti da neoplasia.

Cholesterolaemia values have been investigated in a simple of colon cancer patients and in two control samples consisting of age and sex corresponding subjects suffering respectively from peripheral arteriopathy and minor pathologies (hernias and varices). The study was extended subsequently to a sample of subjects suffering from thyroid neoplasia and two similarly constituted control samples. Cholesterolaemia was significantly lower in colon cancer patients than in the control samples whereas in subjects suffering from thyroid cancer, statistical significance was not attained even though a similar reduction was recorded. The reduction in cholesterol in cancer patients is, in the light of the most recent studies, an effect of cancer on cholesterolaemia, thus giving the lie to the theory that low blood cholesterol is a factor favouring the onset of cancer, and is a finding with by no means indifferent repercussions on the study of the behaviour and physiopathology of cancers.