Impact of microscopic extrathyroidal extension on differentiated thyroid cancer post-surgical risk of recurrence: a retrospective analysis.

PURPOSE: In the last edition of the American Joint Committee on Cancer (AJCC) staging system, differentiated thyroid cancers (DTC) showing microscopic extrathyroidal extension (mETE) are considered comparable to intrathyroidal cancers for their clinical behavior and prognosis. The aim of the study is to evaluate the impact of this updated assessment of T, when applied to the postoperative recurrence risk stratification, according to the American Thyroid Association Guidelines (ATA-RR). METHODS: One-hundred DTC patients who underwent total thyroidectomy were retrospectively evaluated. The downstaging of mETE was introduced in the definition of T, and the updated classification defined as modified ATA-RR (ATAm-RR). For each patient, post-surgical basal and stimulated thyroglobulin (Tg) levels, neck ultrasound (US) and post-ablative 131-I whole body scan (WBS) reports were considered. The predictive performance (PP) of disease recurrence was calculated both for each single parameter, as well as for all of them. RESULTS: According to ATAm-RR classification, 19/100 patients (19%) were downstaged. ATA-RR proved a significant PP for disease recurrence (DR) (sensitivity 75.0%, specificity 63.0%, p = 0.023). However, ATAm-RR performed slightly better due to an increased specificity (sensitivity 75.0%, specificity 83.7%, p < 0.001). For both classifications, the PP was optimal when all the above-mentioned predictive parameters were considered. CONCLUSION: Our results suggest that the new assessment of T considering mETE resulted in a downgrading of ATA-RR class in a significant number of patients. This provides a better PP for disease recurrence, and the best PP was obtained when considering the whole predictive variables together.

Hemithyroidectomy versus total thyroidectomy in the intermediate-risk differentiated thyroid cancer: the Italian Societies of Endocrine Surgeons and Surgical Oncology Multicentric Study.

The surgical treatment of the intermediate-risk DTC (1-4 cm) remains still controversial. We analyzed the current practice in Italy regarding the surgical management of intermediate-risk unilateral DTC to evaluate risk factors for recurrence and to identify a group of patients to whom propose a total thyroidectomy (TT) vs. hemithyroidectomy (HT). Among 1896 patients operated for thyroid cancer between January 2017 and December 2019, we evaluated 564 (29.7%) patients with unilateral intermediate-risk DTC (1-4 cm) without contralateral nodular lesions on the preoperative exams, chronic autoimmune thyroiditis, familiarity or radiance exposure. Data were collected retrospectively from the clinical register from 16 referral centers. The patients were followed for at least 14 months (median time 29.21 months). In our cohort 499 patients (88.4%) underwent total thyroidectomy whereas 65 patients (11.6%) underwent hemithyroidectomy. 151 (26.8%) patients had a multifocal DTC of whom 57 (10.1%) were bilateral. 21/66 (32.3%) patients were reoperated within 2 months from the first intervention (completion thyroidectomy). Three patients (3/564) developed regional lymph node recurrence 2 years after surgery and required a lymph nodal neck dissection. The single factor related to the risk of reoperation was the histological diameter (HR = 1.05 (1.00-1-09), p = 0.026). Risk stratification is the key to differentiating treatment options and achieving better outcomes. According to the present study, tumor diameter is a strong predictive risk factor to proper choose initial surgical management for intermediate-risk DTC.

Morbidity following thyroid surgery: acceptable rates and how to manage complicated patients.

PURPOSE: The endocrine surgeon and the endocrinologist should standardize how they deal with patients with an indication for thyroidectomy, as the road to surgery starts well before the operation itself. The patient should be thoroughly informed about where and how surgery will be performed, the postoperative improvements that can be expected, and the possibility and incidence of relevant complications. This short review aims at identifying the most common postoperative issues after thyroidectomy, with the relevant therapeutic suggestions. METHODS: A revision of studies reporting the morbidity of thyroid surgery, involving the largest numbers of patients. RESULTS: It has been clearly demonstrated that the outcome of thyroid surgery is significantly better when the procedure is performed by an experienced surgeon. Thus, the number of thyroidectomies performed by a surgeon should drive the endocrinologist when referring a patient. CONCLUSIONS: Despite the surgeon's experience, thyroidectomy is burdened by a relatively high rate of postoperative issues ranging from less severe ones to others causing significant changes in the patient's quality of life. Minor, non-invalidating symptoms have been described in 40% of patients after thyroidectomy (e.g. hoarseness, mild dysphagia, some degree of voice alteration); however, these symptoms usually resolve within a few months of surgery, with or without early treatment. On the other hand, major postoperative complications are observed in a limited number of patients, but in these cases early diagnosis is important to provide the most appropriate postoperative treatment, and thus hasten full recovery or at least achieve the greatest possible improvement.

Relationship between circulating anti-thyroglobulin antibodies (TgAb) and tumor metabolism in patients with differentiated thyroid cancer (DTC): prognostic implications.

PURPOSE: TgAb have been proposed as tumor markers in DTC. Recent evidence links TgAb levels with DTC aggressiveness. We aimed to evaluate the relationship between TgAb and tumor glucose metabolism in DTC patients. METHODS: Seventy-one DTC patients who underwent 18F-FDG PET/CT were included. According to TgAb value and trends, patients were divided into TgAb positive (TgAb+) or negative (TgAb-) as well as in patients with increasing (Inc-TgAb) or decreasing (Dec-TgAb) trend. On the basis of the results of FDG-PET, post-therapy 131I and Tg levels, patients were divided into two groups according to the evidence (ED) or absence (NED) of disease. ED patients were further divided into three subgroups: 1. radioiodine avid with positive 18F-FDG PET/CT (PET+/131I+), 2. radioiodine refractory with positive 18F-FDG PET/CT (PET+/131I-) and 3. radioiodine avid with negative 18F-FDG PET/CT (PET-/131I+). MeanSUV of FDG-avid lesions was assessed and averaged for each patient (SUVmean-pt). T test was performed to assess the difference between SUVmean in TgAb-, TgAb+ and in Inc-TgAb and Dec-TgAb subgroups. Difference in TgAb between ED and NED patients as well as between ED patients and PET+/131I+, PET+/131I- and PET-/131I+ subgroups was compared. RESULTS: SUVmean was significantly higher in Inc-TgAb with respect to Dec-TgAb subgroup (5.2 ± 1.5 vs. 2.9 ± 1.1, p < 0.05). TgAb were higher only in the ED PET+/131I+ subgroup with respect to NED patients (p < 0.01). CONCLUSIONS: The relationship between higher tumor metabolism and trend of TgAb supports a prognostic relevance of TgAb in DTC patients. Significantly higher TgAb in radioiodine avid tumors with positive 18F-FDG PET/CT further testify the role of TgAb as surrogate tumor marker in DTC.

Update on the diagnosis and treatment of differentiated thyroid cancer.

During the 1990s, with the general tendency to develop minimally invasive operations, an endoscopic approach has been applied to neck surgery for both parathyroidectomy and thyroidectomy. The most widely spread minimally invasive technique for thyroidectomy is minimally invasive video assisted thyroidectomy (MIVAT), described and developed for the first time at our institution in 1998. Ideal candidates for MIVAT are patients with a thyroid volume lower than 25ml with nodules smaller than 35 mm. Consequently, MIVAT will present restricted indications, being suitable only for the treatment of about 10-15% of the whole standard surgical case load. Thus, together with small follicular lesions, "low risk" papillary carcinoma will result the main indication for MIVAT, being this small cancer usually harboured in normal glands of young females. On the other hand, in case of locally invasive carcinomas and/or lymph node metastasis the procedure must be immediately converted to the conventional technique. MIVAT also is not indicated for the treatment of medullary and anaplastic carcinomas. Recent prospective randomized studies clearly demonstrate that MIVAT allows achieving same clearance at the thyroid bed level and same outcome as conventional technique, when dealing with "low risk" papillary carcinoma. At the same time, patients can benefit from the main advantages of this minimally invasive technique: lower postoperative pain, faster postoperative recovery and excellent cosmetic outcome.

The impact of thyroidectomy on psychiatric symptoms and quality of life.

INTRODUCTION: Existing trials investigated the impact of medical treatment of thyroid disorders on health-related quality of life (QOL) and psychiatric symptoms. The aim of this prospective study is to analyze the impact of thyroid surgery on QOL and severity of psychiatric symptoms. MATERIALS AND METHODS: Forty-seven patients undergoing thyroid surgery (TS) were assessed before thyroidectomy (T0) and 37 also after surgery, >or=6 months after euthyroidism was achieved (T1). QOL and psychiatric symptoms were evaluated at T0 and T1 using the Medical Outcomes Study Short Form Survey (SF-36) and the Symptom Checklist-90 (SCL-90-R). Scores at T0 were compared with those of patients undergoing surgery for non-thyroidal disease and the SF-36 scores were also compared with the normative Italian sample. Changes in QOL and psychiatric symptoms between T0 and T1 were also examined. RESULTS: Health-related QOL in TS patients before surgery was poorer than in the comparison group on the SF-36 mental component summary measure and social functioning. Mental health improved significantly after surgery but social functioning remained markedly impaired. A significant reduction in the severity of psychiatric symptoms was observed. DISCUSSION: Our results indicate that even long after euthyroidism is achieved after surgery, patients show a significant improvement of mental health and a reduction of psychiatric symptoms. Nevertheless, patients continue to have a poorer QOL compared to the Italian normative sample.

The impact of thyroidectomy on parathyroid glands: a biochemical and clinical profile.

INTRODUCTION: An evaluation of PTH levels during thyroid surgery may reflect the functional status of the parathyroids and be useful in identifying patients at risk for hypocalcemia. This study aims to monitor the parathyroid function during total thyroidectomy through intra-operative serial samples for calcium and PTH. MATERIALS AND METHODS: Forty-seven patients undergoing total thyroidectomy for different diseases were selected for the study. Patients underwent serum PTH and calcium sampling at the induction of anesthesia (T0) and after the first (T1) and the second (T2) lobectomy. Serum calcium was also drafted 24 h after the operation. RESULTS: Mean PTH at T0, T1, and T2 was, respectively: 32.1 pg/ml, 19.6 pg/ml, and 11.5 pg/ml. PTH was significantly higher at T0 when compared to T1 (p<0.0001). It was also significantly higher at T1 than at T2 (p<0.0001). At T1 PTH levels were below the normal range in 20/47 cases (42.5%) and at T2 in 31/47 cases (66%). Twenty-four h after surgery, 8 patients (17%) demonstrated a biochemical hypocalcemia. A PTH value at T0 in the upper (>70 pg/ml) or in the lower (<20 pg/ml) limits of the normal range was statistically related to post-operative hypocalcemia (p=0.017). DISCUSSION: The study seems to confirm that serum PTH during thyroidectomy does not represent a sensitive tool in precociously identifying hypocalcemic patients. Nevertheless, before surgery, a PTH concentration at the higher or lower normal limit may help to identify patients "at risk" of developing hypocalcemia.

Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in pregnancy.

The association of pheochromocytoma (PHEO) and pregnancy is uncommon and life threatening for both the fetus and the mother. Early diagnosis and treatment is essential to decrease maternal and fetal mortality and to differentiate the disease from the more common pre-eclampsia. While medical treatment should be started immediately after diagnosis, the timing of surgical treatment is still debated. We describe the case of a 27-yr-old woman in the 18th week of pregnancy who showed a biochemical pattern typical of PHEO and, by imaging studies, 2 tumors with the same characteristics: the first localized on the right adrenal gland, the second at the right renal hilum. The patient underwent surgery because of suspicion of malignant PHEO with local metastasis, while histology revealed a rare association of a solitary PHEO and para-aortic neurofibroma, both tumors embryologically deriving from a common cell precursor.

Familial parathyroid hyperplasia: is there a place for minimally invasive surgery? Description of the first treated case.

While the majority of patients affected with sporadic primary hyperparathyroidism (sPHPT) can be selected for minimal access surgery, patients affected with 4-gland hyperplasia still do not represent an indication for it. Minimally invasive video-assisted parathyroidectomy (MIVAP) was introduced in 1996; this technique relies on a single central incision and external retraction and therefore allows a bilateral neck exploration. This was the case of a 27-yr-old female with familial primary hyperparathyroidism (FPHPT). Three enlarged glands were immediately identified in orthotopic positions and the fourth was intrathyroideal. A subtotal parathyroidectomy was then performed, leaving a small fragment of the inferior right gland and completed with the cervical thymectomy by inverting the positions of the camera and the retractor assistants with regard to the positions originally described. Quick intraoperative PTH assay (QPTH) confirmed the surgical cure of the disease.

Video-assisted thyroidectomy for Graves' disease: report of a preliminary experience.

BACKGROUND: Ever since the introduction of video-assisted thyroidectomy (VAT), Graves' disease has represented a contraindication. This study aimed to demonstrate that VAT can be proposed also for Graves' disease. METHODS: From January 2002 to March 2003, 21 patients (20 women and 1 man) with Graves' disease underwent VAT. One patient showed positive test results for gene RET. The mean age of the patients was 36.4 years. RESULTS: No conversions of procedure were necessary. The mean operative time was 56.9 min. The RET-positive patient underwent total thyroidectomy and central compartment lymphadenectomy. Postoperative bleeding occurred in the patient with the largest gland. Histology showed goiter in 18 cases, medullary carcinoma in 1 case, and papillary carcinoma in 2 cases. No cases of vocal cord palsy but three cases of transient hypocalcemia were registered. CONCLUSIONS: Graves' disease can be treated safely using VAT only if selection criteria are carefully respected. The young age of the patients with this disease encourages us to propose VAT for its good cosmetic and postoperative outcome.

[Minimally invasive video-assisted thyroidectomy--techniques and results over 4 years of experience (1999-2002)]. / Tiroidectomia video-assistita minimamente invasiva (Mivat)--cenni di tecnica an e risultati di 4 anni di esperienza (Analisi della casistica 1999-2002).

INTRODUCTION: This study reviews four years of Minimally Invasive Video Assisted Thyroidectomy (MIVAT) technique and compares the results to those of traditional thyroid surgery. MATERIALS AND METHODS: Between 1999 and 2002, a series of 427 patients were submitted to MIVAT at our Department. Selection criteria were: thyroid nodule maximum diameter of 3.5 cm, total thyroid volume under 25 cc, no signs associated thyroiditis, diagnosis of benign thyroid disease or "low risk" thyroid tumor, no evidence of nodal disease of the neck. RESULTS: We operated on 362 females and 65 males and the mean age of the population was 39.6 years (range 10-77). A total thyroidectomy was performed in 208 cases, and 219 patients underwent a single-side procedure. Mean operative time was 30.4 minutes for lobectomy (range 20-140 minutes) and 50.2 for total thyroidectomy (range 35-140). Complications were represented by definitive recurrent nerve palsy in 3 patients (0.7%) and one case of definitive hypoparathyroidism (0.4%). A wound infection is reported in 3 cases and we had no major bleeding that required surgical revision. A conversion to open procedure was performed in 5 cases (1.2%); mean hospitalisation was 1.28 days (range: 1-4). CONCLUSIONS: This series demonstrates that MIVAT is not different to conventional open surgery in terms of complications, radicality of the procedure and operative time. Moreover, even if not statistically proved, MIVAT appears to offer some advantages in terms of cosmetic results and postoperative pain. In conclusion, we believe that MIVAT is a perfectly reproducible and safe technique for both benign and low-risk malignant thyroid disease, when correct indications are strictly followed.

[Video-assisted minimally invasive parathyroidectomy with median access. Technical changes: case load 1999-2002]. / Paratiroidectomia miniinvasiva videoassistita con accesso mediano. Evoluzione tecnica: casistica 1999-2002.

INTRODUCTION: In 1997 a Minimally Invasive Video Assisted Technique for Parathyroidectomy (MIVAP) was developed in the University of Pisa. In this review we examine the last three years of MIVAP (240 cases) in order to identify the advantages and the limits of the procedure after the first-period development of the technique. RESULTS: In our experience, 65% of patients affected by primary hyperparathyroidism (PHPT) turned out to be eligible for MIVAP. During the first years several selection criteria were strictly followed; more recently, some initially absolute contraindications to the operation have been interpreted more flexibly. Mean operative time is 35 minutes. 18 conversions (7.5%) to traditional open cervicotomy were needed and in 4 cases (1.6%) no affected parathyroid tissue was removed. CONCLUSIONS: At present, we consider absolutely necessary for MIVAP: preoperative localization of an adenoma with at least one imaging study (US or MIBI scintiscan) and the availability of QPTH intraoperative assay. No absolute contraindications other than the size of the lesions and the suspect of parthyroid carcinoma are identified for patients with PHPT. Moreover, MIVAP has proved to have further advantages when compared to other mini invasive procedures such as the demonstrated possibility to perform a traditional bilateral exploration, when indicated. Nevertheless, a great degree of experience is requested for this procedure. In conclusion, MIVAP permits to significantly reduce postoperative pain, size of the incision, days of hospitalisation and, finally, the cost of the entire procedure without affecting in any way the success rate of the traditional operation and without an increase of the complications.

[Intraoperative use of radiofrequency thermoablation of liver tumors: considerations on indications and related therapeutic aspects]. / L'impiego intraoperatorio della termoablazione a radiofrequenza di neoplasie epatiche: considerazioni su indicazioni ed aspetti terapeutici associati.

PURPOSE: To evaluate the usefulness of intraoperative radiofrequency thermoablation of liver tumours in association or not with hepatic resection. MATERIALS AND METHODS: 21 patients were treated between January 1998 and December 2001, there were 4 hepatocellular carcinoma and 17 metastasis. In 13 cases radiofrequency was associated to hepatectomy, in 3 cases to resection of extraepatic disease and in 5 cases were performed alone. 23 lesions were treated by radiofrequency (range 1-3); the mean dimension was 26 millimetres (range 8-70). A clamping of the liver pedicle was always done. RESULTS: There were no operative deaths, 3 (14.3%) patients developed complications related to radiofrequency (2 biliary leakages, 1 hepatic abscess). 14 (66.7%) patients were alive after a mean follow up of 14.5 months, 2 of all (9.5%) had a recurrence in the site previously treated with thermoablation. Association between hepatectomy and radiofrequency increased the number of curative liver resections from 10.1% to 16.3% (in case of colorectal metastasis). DISCUSSION: Intraoperative radiofrequency is useful to increase the number of curative hepatectomies, to treat liver masses which demonstrate unresectable or found by ultrasonography at the operating time and even to reach tumours difficult to manage by percutaneous approach. In any case the aim is to obtain the absence of macroscopic neoplastic disease (RO status). It is a safe and effective therapeutic strategy, anyway all procedures and indications are still not completely cleared. CONCLUSIONS: Intraoperative thermoablation of liver tumour is safe and effective and increases therapeutic the number of curative hepatectomies. Further progresses may improve the efficacy and extend the indications of this strategy.

Parathyroid cyst, a case report and review of the literature.

Parathyroid cysts are rare, representing 1% of all neck swellings. A correct preoperative diagnosis is rarely formulated, especially because of the non-specific clinical and ultrasonographic findings; for this reason, patients are often submitted to surgery for thyroid nodules. In the present report we describe a case where the preoperative diagnosis was correctly formulated following the aspiration and PTH assay of clear, colorless, watery fluid from the cyst. While cyst aspiration is considered the elective treatment for these lesions, recurrences being uncommon, surgery was indicated in the present case because of two recurrences after aspiration and the onset of compressive symptoms. Cystic masses of the neck should be accurately diagnosed to recognize their true nature and to allow their correct and non-invasive treatment: surgery is indicated only when recurrences and symptoms are present. Indications for aspiration of all solitary cysts of the neck should be considered to correctly identify their nature.

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.

Intraoperative decay profile of intact (1-84) parathyroid hormone in surgery for renal hyperparathyroidism--a consecutive series of 80 patients.

BACKGROUND: The utility of intraoperative parathyroid hormone (PTH) monitoring is unclear in the surgical management of renal hyperparathyroidism. Our goal was to define the normal pattern of decay during operation for renal hyperparathyroidism by using the rapid intact (1-84) parathyroid hormone (PTH) assay. METHODS: Eighty consecutive patients underwent neck exploration for renal hyperparathyroidism. Intact PTH levels were monitored with a rapid immunochemiluminometric assay. Samples were assayed at the induction of anesthesia, after dissection before resection, and 20 and 40 minutes after resection. Follow-up ranged from 3 to 24 months. RESULTS: Twenty minutes after resection, PTH levels remained many-fold supranormal. Seventy-seven patients (96%) were cured. Of these, 75 patients (94%) had PTH decay of more than 50% from the preoperative level; 74 (99%) were cured. Only 1 of 3 patients (33%) in whom the PTH level decreased less than 40% from the preoperative level was cured. Two patients had intermediate values and both were cured. CONCLUSIONS: The intraoperative decay of PTH during operation for renal hyperparathyroidism is slower than for patients with normal renal function. However, 20 minutes after resection, a decline to less than 50% of the preoperative level predicts cure, while a level greater than 60% predicts failure.

Coupling of electron transfer with proton transfer at heme a and Cu(A) (redox Bohr effects) in cytochrome c oxidase. Studies with the carbon monoxide inhibited enzyme.

A study is presented on the coupling of electron transfer with proton transfer at heme a and Cu(A) (redox Bohr effects) in carbon monoxide inhibited cytochrome c oxidase isolated from bovine heart mitochondria. Detailed analysis of the coupling number for H(+) release per heme a, Cu(A) oxidized (H(+)/heme a, Cu(A) ratio) was based on direct measurement of the balance between the oxidizing equivalents added as ferricyanide to the CO-inhibited fully reduced COX, the equivalents of heme a, Cu(A), and added cytochrome c oxidized and the H(+) released upon oxidation and all taken up back by the oxidase upon rereduction of the metal centers. One of two reductants was used, either succinate plus a trace of mitochondrial membranes (providing a source of succinate-c reductase) or hexaammineruthenium(II) as the chloride salt. The experimental H(+)/heme a, Cu(A) ratios varied between 0.65 and 0.90 in the pH range 6.0-8.5. The pH dependence of the H(+)/heme a, Cu(A) ratios could be best-fitted by a function involving two redox-linked acid-base groups with pK(o)-pK(r) of 5.4-6.9 and 7.3-9.0, respectively. Redox titrations in the same samples of the CO-inhibited oxidase showed that Cu(A) and heme a exhibited superimposed E'(m) values, which decreased, for both metals, by around 20 mV/pH unit increase in the range 6.0-8.5. A model in which oxido-reduction of heme a and Cu(A) are both linked to the pK shifts of the two acid-base groups, characterized by the analysis of the pH dependence of the H(+)/heme a, Cu(A) ratios, provided a satisfactory fit for the pH dependence of the E'(m) of heme a and Cu(A). The results presented are consistent with a primary involvement of the redox Bohr effects shared by heme a and Cu(A) in the proton-pumping activity of cytochrome c oxidase.