Completion thyroidectomy for differentiated thyroid cancer (results in a consecutive series of 68 patients).

INTRODUCTION: Completion thyroidectomy plays an important role in the management of patients with thyroid cancer. The aim of this study is to determine the indications for and timing of a second surgery, as well as surgical complications. MATERIAL AND METHODS: Operative reports, as well as the hospital and outpatient records of 686 consecutive patients, who had undergone surgery for differentiated thyroid cancer, were reviewed. Among these, 68 (9,9%) patient records of a completion thyroidectomy for cancer were analyzed. RESULTS: The mean time interval between the first and second operation was 3.6 months (range: 1-9). Post-operative complications occurred in 9 patients (12,9%). Among three patients with inferior laryngeal nerve palsy (4,4%) one had definitive palsy (1.4%). Hypoparathyroidism occurred in 6 patients (8,8%) being permanent in one of them (1.4%). No significant difference either for definitive inferior laryngeal nerve lesions (p = 0.9) or for definitive hypocalcemia (p = 1) was found between the groups of patients who had a completion thyroidectomy and those who had a one-step total thyroidectomy for cancer. CONCLUSIONS: Correct indications for re-operation, total lobectomy as a primary surgical procedure as well as lateral access to the residual thyroid gland could all reduce the high risks of complications related to this kind of surgery.

[Lymphadenectomy in differentiated thyroid carcinoma]. / La linfectomia nel carcinoma differenziato della tiroide.

Differentiated thyroid carcinoma accounts for 90% of all thyroid cancers and occurs as papillary carcinoma in 90% of cases. It was shown as this is characterized by an excellent long-term prognosis, although in follow-up long series, were described recurrence rates up to 35%. Although in the past has not been attributed prognostic significance to the lymph nodes, in the last decade has shown how these can affect the rate of locoregional recurrence of differentiated thyroid carcinoma. This renewed interest in lymph node metastatic disease has prompted a shift in surgical treatments more aggressive, with a view to achieving a low incidence of locoregional recurrence. Analyzing the more recent guidelines formulated at the international level, we can highlight how we gradually consolidated the role of prophylactic central compartment lymphadenectomy in the surgical treatment of patients with differentiated thyroid carcinoma. The aim of this treatment, in fact, is not only to reduce the mortality of patients, but to obtain an adequate staging, facilitate radiotherapy treatment, obtain undetectable thyroglobulin levels, avoiding the need for repeated reiterventi, made more simple follow-up. All these objectives can be achieved by careful surgery. Total thyroidectomy associated with prophylactic lymphadenectomy of the central compartment was found to achieve these objectives, although in the absence of data from randomized trials, its role remains controversial.

Prioritizing surgical waiting lists.

RATIONALE, AIMS AND OBJECTIVES: This paper deals with the problem of surgical waiting lists and is aimed, in particular, at comparing two different prioritization approaches: (1) the clinical assessment of treatment urgency aimed at categorizing patients into urgency-related groups (URGs) with a given recommended maximum waiting time for treatment; and (2) the implementation of an original prioritization scoring algorithm aimed at determining the relative priority of each patient in the waiting list and the corresponding order of admission. METHODS: A modelling exercise based on a cohort of 236 patients enrolled on the waiting list of a surgical department in an Italian public university hospital, from 1 January to 30 June 2004, is presented. The comparison is based on a measure called need-adjusted-waiting-days, which allows to take into proper account both urgency and priority. RESULTS: The results show that both methods should be implemented simultaneously for increasing the department's performance in terms of both efficiency--outcome gained from a given amount of resources--and equity--how patients are admitted according to their need. CONCLUSIONS: Waiting list prioritization should not be limited to classifying patients into URGs, but to using a scoring system as well, in order to schedule patient admissions in an explicit and transparent way.

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use.

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

Absence of histological malignancy in a patient cohort with follicular lesions on fine-needle aspiration.

Follicular lesions account for 4-6% of all thyroid fine-needle aspiration (FNA) cytologies. To date, no cytological criteria exist to distinguish follicular adenoma from carcinoma. For this purpose, histological evaluation after surgical exeresis is required. From 1993 to 2000 we performed 1,238 US-assisted FNA biopsies in patients admitted to our unit for uni- or multi-nodular goiters. In the latter goiters, FNA was performed in the dominant nodule. Cytological examination revealed a follicular lesion in 71 patients (5.7%). All patients came from regions of Northern Italy with moderate iodine deficiency. In 48%, the lesion presented as a solitary nodule, while in the other 52% it occurred in the context of a multinodular goiter. Surgical exeresis of the neoplasm was recommended in all cases. Sixty-three patients (89%) underwent surgery (Group 1) while the other 8 patients (11%) opted for follow-up (Group 2). In Group 2, the mean nodule volume (3.2 +/- 0.5 ml) at baseline was slightly smaller (p = 0.08) than that found in Group 1 (5.4 +/- 0.7 ml). In Group 1, histological examination after surgery showed a follicular adenoma in 52 patients (83%) and a colloid goiter in the others (17%). No malignancy was detected. Group 2 underwent a median follow-up of 46 months (range 24-96 months) on L-thyroxine suppressive regimen (dose range 75-125 pg/day), with TSH levels ranging from 0.1 to 0.3 mlU/l. Throughout the follow-up, no patient developed clinical or ultrasonographic features that could be considered worrisome for malignancy; thus, no further biopsy was performed. However, an overall slight increase (median +5.2%) in nodular volume in respect to baseline was observed. Although institutional and cytological bias cannot be ruled out, our data do not confirm the reported incidence of malignancy in histological specimens of follicular lesions diagnosed on FNA cytology, and prompt us to suggest a less aggressive first-step approach (i.e. careful clinical and instrumental evaluation, and suppressive L-T4 therapy) for these lesions, unless anamnestic reports or clinical and ultrasonographic features of the nodules suggest malignancy.

[13 cases of angiodysplasia of the digestive system]. / Su 13 casi di angiodisplasia dell'apparato digerente.

OBJECTIVE: This clinical study assesses the diagnostic and therapeutic problems entailed in so-called gastrointestinal angiodysplasias. Summary back ground data: the topic presents numerous, still unresolved, issues: classification (its clinical presentation and classification); anatomo-pathological identification; diagnosis and localization; treatment of patients with acute massive bleeding; long-term outcomes. MATERIALS AND METHODS: Thirteen patients, equally distributed between both sexes an with a mean age of 54 years (range = 23-75), were observed and operated over a nearly 20 year period. All patients had acute massive bleeding localized to the stomach, duodenum, ileum, colon and rectum. Diagnosis and localization were previously obtained in nine patients, mostly using selective angiography. With the exception of two rectal localizations treated with embolization, all patients underwent surgical resection. In two cases operated on without previous diagnosis, (rebleeding occurred). CONCLUSION: The data available in the literature are broadly substantiated, even if the mean age reported seems somewhat lower (54 yrs). Localizations were detected in nearly all segments of the gastrointestinal tract, and the indication to surgical resection possibly after detection of the angiodysplasia and source of bleeding is confirmed. The best diagnostic technique is selective angiography.

Doppler evaluation of intrathyroid arterial resistances during preoperative treatment with Lugol's iodide solution in patients with diffuse toxic goiter.

BACKGROUND: The aim of this study was to ascertain the utility of echo-Doppler in the analysis of the low resistance thyroid vascularization in diffuse toxic goiter (DTG), and the effectiveness of Lugol's solution (iodine-iodide solution) in patients undergoing thyroidectomy. STUDY DESIGN: Twenty-five patients with diffuse toxic goiter were evaluated and compared with 19 normal subjects. Patients were treated with increasing doses of Lugol's solution 2% for 7 days until a total dose of 75 mg of iodine was given. Echo-Doppler was performed on the last day of treatment, 12 hours before operation. RESULTS: Mean basal Doppler Resistance Index (RI) of intrathyroid arterial flow was significantly lower in patients with DTG compared with normal controls (0.4718 +/- 0.0625 versus 0.55 +/- 0.05, range: 0.472 to 0.643; p = 0.008). Moreover, the RI was significantly increased in patients with DTG after Lugol's solution (+16.46 +/- 10.22%, range: -2.59 to +39.97; p< 0.0005). CONCLUSIONS: Echo-Doppler RI allowed documenting lower arterial resistances within the thyroid gland in patients with DTG. The use of preoperative Lugol's solution therapy induces normalization of those changes for safer thyroidectomy.

Cervico-mediastinal extension of thyroid cancer.

A surgical series of 30 cervico-mediastinal thyroid cancer patients operated on has been retrospectively reviewed. Results were compared with those obtained in patients operated on for benign cervico-mediastinal goiter and thyroid cancer confined to cervical region. Of 4688 thyroidectomies performed, 30 patients were operated on for thyroid carcinoma with cervico-mediastinal extension. There were 15 males and 15 females. The mean age was 67 years (range, 21-86 years). Patients with cervico-mediastinal cancer were significantly older than patients with benign cervico-mediastinal goiter (P < 0.0001). Time between onset of first symptoms and surgery was significantly longer in patients with cervico-mediastinal cancer than in those with benign cervico-mediastinal goiter (P < 0.0001) and cervical thyroid cancer. Signs and symptoms at the time of surgery were cervical mass in 28 patients (93%), cervical lymphadenopathy in 20 patients (66%), dyspnea in 21 (70%), dysphagia in 9 (30%), dysphonia in 2 (7%), and venous stasis in 1 (3%). None of the patients was asymptomatic. Total thyroidectomy with functional lymphectomy was performed in 16 cases. Seven of these patients were operated on in 2 stages. In 8 cases the operation was a debulking procedure, and in 6 it was a near-total thyroidectomy. Sternotomy was performed in two cases. A differentiated thyroid cancer was found in 21 patients (70%), medullary in 5 (17%) and undifferentiated in 4 (13%). The incidence of medullary carcinoma was significantly higher compared with cervical cancer (P < 0.008). Postoperative complications were higher than those occurring in benign cervico-mediastinal goiter and similar to those occurring in cervical cancer. The actuarial survival was similar to that of cervical cancer matched for age and sex. This analysis shows that the longer clinical history of goiter is related to its endothoracic development and its neoplastic transformation. This finding should further encourage surgeons to treat any cervico-mediastinal goiter as promptly as possible.

Pseudotumor of the liver: a challenging diagnosis.

Inflammatory pseudotumors of the liver are rare, and their natural history is mostly unknown. Making the diagnosis is often difficult, and these masses are often confused with other lesions, generally either primary or secondary neoplasms. The case of a patient who had an exhaustive preoperative work-up, including ultrasonography, CT scan and MRI, is herein presented. The characteristics of each exam, particularly those of the MRI, in which the pattern is poorly described in the literature, are reported. A fine needle biopsy was not contributive, as it was performed too centrally within the nodule. Only a high degree of suspicion and the existence of this tumor might lead to a preoperative diagnosis, thus avoiding major surgery. However, as is evident from the experiences of most authors and from our own, doubt may persist even after an exhaustive work-up. Since the morbidity and mortality of liver resection of noncirrhotic livers is low, surgery should be considered the treatment of choice.

SCC antigen in malignant and nonmalignant squamous lesions.

Squamous cell carcinoma (SCC) antigen (Ag) present and expressed in normal epithelium and epithelial tissues is used primarily as tumor marker of SCC of the uterine cervix. In this review, we considered factors interfering in vitro with the collection of samples and assay procedures, benign and malignant nongynecological diseases which may be the cause of elevated serum levels of SCC Ag. Contamination with skin or saliva strongly influences SCC Ag levels. SCC Ag is elevated in several benign lesions, including pulmonary (tuberculosis, adult respiratory distress syndrome, pulmonary infiltration with eosinophilia, sarcoidosis, bronchogenic cyst) and skin (eczema, pemphigus, erythroderma epidermitis, psoriasis) diseases. Elevations are observed in SCC malignancies of the head and neck, esophagus, skin, lung, urothelium, anal canal and vulva.

Toxic thyroid adenoma: absence of DNA mutations of the TSH receptor and Gs alpha.

DNA point mutations of the TSH receptor and of the alpha subunit of the stimulatory GTP-binding protein (Gs alpha) have been suggested as major causes of hyperfunctioning thyroid adenomas. However, significant differences in the prevalence of these mutations (from 0.3 to 84%) have been found in different populations. The present study was designed to evaluate further the presence of mutations in discrete fragments of cDNA encoding critical regions of the TSH receptor and of the Gs alpha involved in signal transduction and cAMP production. Genomic DNA extracted from 15 thyroid adenomas and surrounding quiescent thyroid tissues was used as a template to amplify four DNA fragments of TSH receptor and one DNA fragment of Gs alpha. TSH receptor and Gs alpha DNAs were analyzed by a number of techniques. We did not detect any mutations (new or previously described) in our patients. These results confirm that the causes of solitary toxic adenomas are protean, and only some of them may be somatic DNA point mutations. Since the clinical features of solitary toxic adenoma are homogeneous, it could be important to establish the specific molecular defect underlying each case, in order to follow up the patients and to assess their clinical evolution.

Combined use of urinary UGP and serum CA 125 in the diagnosis of gynecological cancers.

UGP, the beta-core fragment of human chorionic gonadotropin has been proposed as a tumor marker for gynecological malignancies. This fragment may be detected in a single morning-specimen of urine using an enzyme immunoassay. In this study, the diagnostic usefulness of urine UGP and serum CA 125 measurement for gynecological neoplasias (149 cases) was evaluated using a control group of patients with benign gynecological diseases (69 cases) and healthy females (99 cases). Considering the neoplastic patients in comparison to patients with benign diseases, the best diagnostic efficiency (78%) was found to correspond to a cut-off level of 120 pmol/mol creatinine the sensitivity being 73% and the specificity 90%. With this cut-off, an efficiency of 82% for healthy controls was obtained. Since the menopausal condition increases UGP levels, and though no significant difference for UGP was found between healthy subjects and patients with benign diseases, we decided to consider the reference populations as a single group. Thus, we evaluated the UGP performance on the basis of menopausal status. When a specificity of 95% was fixed, the cut-off values were 120 and 180 pmol/mol creatinine for pre- and postmenopausal women respectively, the sensitivity being 73% and 64%. Finally the combined evaluation of UGP and CA 125 improved their individual clinical efficiency for the diagnosis of ovarian serous cystadenocarcinomas, assuring a sensitivity of 86% and a specificity of 89%.

[Recurrent goiter: analysis of 134 reinterventions]. / Il gozzo recidivato: analisi di 134 reinterventi.

Reoperative surgery for thyroid disease still plays a predominant role in the treatment of goiter recurrences. At the moment, neither useful biological nor clinical indicators exist to prevent such recurrences. The effectiveness of TSH-suppressive therapy is still debatable and some authors have proposed total thyroidectomy for this benign disease in order to eliminate the risk of relapse. We analyzed 134 patients who underwent reintervention for recurrence of goitre in order to: 1) study possible clinical or epidemiological characteristics that could influence recurrence, 2) to verify the indications to reoperation, and 3) to evaluate the incidence of complications. For the study of complications, we adopted as a control group a series of 361 patients operated on by the same medical staff and undergoing subtotal thyroidectomy for multinodular goitre, with a minimal follow-up of 10 years. The surgical technique is described and several peculiarities are discussed. In the group of patients who had reoperation two cases (1.5%) of laryngeal palsy and two cases (1.5%) of hypoparathyroidism were recorded and this was not significantly different from the control group. A positive correlation was found between recurrence and young age at the time of first surgery (p < 0.006), female sex (p = 0.045) and esthetic results (p = 0.013). No further clinical recurrence was found in 101 patients after a mean follow-up of 122 months, while in 16 cases the echography revealed nodules in the residual parenchyma. In our opinion total thyroidectomy is not justified as a first standard procedure for this benign disease caused by the activity of various not yet well understood, growth factors.

[Surgical treatment of cervico-mediastinal goiter]. / Il trattamento chirurgico del gozzo cervico-mediastinico.

Over the last decades definitions and classifications of cervico-mediastinal goiters have been proposed. According to the definition of Valdoni and Tonelli, from 1968 to 1991 237 patients were operated on for cervico-mediastinal goiter. There were 168 simple forms (141 anterior and 27 posterior) and 69 complex forms according to Borrelly's classification. We analyse and discuss the clinical presentation, the diagnostic procedures and the surgical technique in relation to post-operative complications and long term results. The mean duration of symptoms before surgery in patients with cervico-mediastinal goiter was longer than in subjects with cervical goiters. All but 8 operations were performed through a cervical incision. Two patients, both with advanced tumor, died postoperatively. Post-operative complications were: hemorrhage 0.8%, dysphonia 4.6% and transient hypoparathyroidism 2.9%. A clinical follow-up was available for 194 patients. Permanent dyspnea was observed in 1.0%, dysphonia in 4.6% and transient hypoparathyroidism in 2.9%. Tracheotomy was necessary in 5 cases. Complications were more frequent after total thyroidectomy than after partial resection (p < 0.05), after surgery for malignancy than for benign disease (p < 0.05) and in complex than in simple forms (p < 0.05). Almost all cervico-mediastinal goiters can be treated by a cervical incision. Sternotomy, when required, does not influence mobility and mortality. The lacking of an alternative treatment, the relatively high incidence of malignancy and the risk of acute airway obstruction should induce the early removal of all substernal goiters.

[Surgical treatment of multinodular goiter]. / Il trattamento chirurgico del gozzo multinodulare.

A homogeneous series of 361 patients operated on for multinodular goitre was analyzed. Minimum and mean follow-up were 10 and 18.6 years, respectively. In most cases a subtotal or near total thyroidectomy was performed, while total thyroidectomy was reserved for patients with cancer. The goal of the study was to verify the long term outcome of this therapeutic strategy in terms of complications, disease recurrence, need of complementary therapies (TSH-suppressive or substitutive) and reinterventions. Global recurrences were 14.7%, and 4.9% of these needed a second operation for indications similar to those of the first operation. Long term complications were vocal cord palsy 1.1% and permanent hypoparothyroidism 0.3%, while the global complications of reinterventions were 3% (n.s.). Nearly half of the patients had not followed any functional or instrumental check-up for at least 5 years nor undergone any hormonal therapy. Among the patients who had a TSH-suppressive therapy, the recurrence rate was not significantly different compared to the group that had no treatment. On the basis of these data, it seems that subtotal thyroidectomy is adequate intervention for multinodular goitre, as long as the number of clinical recurrences is not significantly high. On the contrary, it might be expected that total interventions, performed in non specialized centers, would introduce a higher rate of complications. The need for TSH-suppressive therapy to reduce recurrences was not proven.

[Preliminary experience with a new tumor marker in obstetrics and gynecology: UGP (Urinary Gonadotropin Protein)]. / Esperienze preliminari con un nuovo marcatore tumorale in ostetricia e ginecologia: UGP.

AIM: To evaluate the use of UGP (urinary gonadotropin protein) as a tumor marker in gynaecologic and obstetric malignant diseases. MATERIALS AND METHODS: The study was carried out in the division of Gynaecology and Obstetrics of the Ospedali Riuniti in Bergamo. 63 patients, with obstetric or gynaecologic benign or malignant diseases, entered the study. 66 healthy volunteers were examined as a group-control. In both the groups UGP levels were determined in morning urine, using an immunoenzymatic commercial kit. RESULTS: Results, expressed in fmol UGP/ml of urin, show that UGP is produced by several neoplasms, but the false-positive percentage is still high; a higher precision can be obtained with an accurate choice of the cut-off value and with a standardization of the analytical technics. Besides, the contemporary determination of UGP and CA 125 levels reduces the possibility of false-positive and false-negative results. CONCLUSIONS: More studies must be carried out to confirm the value of UGP as a tumor marker in obstetrics and gynaecology. Anyway, this recently purified protein can already be useful, in combination with the usual tumor markers, in the prompt diagnosis and management of primary neoplasms or recurrences, with a higher sensibility in comparison with traditional clinical and radiological examinations.

A new technique for intraoperative blood recovery in the cancer patient.

Homologous blood transfusion in the cancer patient is dangerous because of an apparent immunodepressive action. Even a program of pre-deposit and isovolemic hemodilution, for reasons of immediacy and patient conditions, is often not feasible. Likewise, the intraoperative recovery of blood, although used by some, does not prevent the possible reinfusion of suspended neoplastic cells. A system that eliminates tumor cells could enable the recovery of blood in cancer patients in non-septic operative sites. A system that seems to correspond to these requisites has been set up by inserting two filters for the elimination of leucocytes from erythrocyte concentrates into a cell separator that is normally used in clinical practice. Laboratory studies, using immunohistochemical identification of tumor cells cultivated in vitro, have demonstrated the absence of contaminating cells in blood available for reinfusion.