Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

Mid-term clinical and radiographic outcome of metal-on-metal hip resurfacing through an anterolateral approach.

PURPOSE: The aim of this retrospective study was to evaluate the medium-term clinical and radiographic results of current generation metal-on-metal resurfacing prostheses performed through anterolateral approach. MATERIALS AND METHODS: Fifty-seven hips in 52 patients underwent resurfacing arthroplasty. Two patients died from unrelated causes, leaving 55 hips in 35 males (3 bilateral) and 15 females (2 bilateral), with a mean age at surgery of 56.2 years (range, 27-70 years). Clinical and radiographic assessment was carried out preoperatively and at follow-up in all the survived cases. The cumulative survival rate was determined according to the method of Kaplan-Meier. RESULTS: At a mean follow-up of 5.2 years (range, 1.8-9.1 years), 2 HRs of the same female patient were revised because of early loosening of the acetabular component. Deep venous thrombosis and transient femoral nerve palsy occurred both in 1 case. No specific complications of HR were observed. Average Harris hip score improved significantly from 59.8 points (range, 30.4-90.6) preoperatively to 93.7 points (range, 53-100) at the latest examination. Neck narrowing showed an average of 3.27%, but it never exceeded 10%. Nonprogressive acetabular radiolucencies and osteolysis were detected both in 2 hips. A high rate of patients (32, 60.4%) developed heterotopic ossifications, although low-grade in most cases (27, 84.4%). The cumulative survival rate at 9.1 years with revision for any reason as the end point was 93.0%. CONCLUSIONS: The early clinical and radiographic results of modern metal-on-metal hip resurfacing performed through an anterolateral approach are promising, but longer-term follow-up studies are necessary.

Histological pattern and gene expression profiling of thyroid tissue in subjects with obesity.

PURPOSE: Subjects with obesity may exhibit an increase in serum TSH concentrations. Several mechanisms have been proposed to explain this association, including the presence of a compensatory mechanism to counterbalance an accelerated turnover of thyroid hormones in subjects with obesity. This study aimed at evaluating whether the thyroids of subjects with obesity differs from those of normal-weight individuals regarding histology and gene expression profiling. METHODS: Ninety-eight patients were selected among those scheduled for thyroidectomy. At histology, thyroid tissue samples were investigated for the presence of adipocytes and/or lymphocyte infiltration. In a subset of patients, the expression at mRNA level of several genes involved in metabolic pathways and immune cell-related mechanisms was quantified by NanoString Technology. RESULTS: The presence of adipose cells was documented in thyroid specimens from 40% normal weight, 52.9% overweight and 73.5% patients with obesity. The number of infiltrating adipocytes was greater in specimens of patients with overweight or obesity compared to normal weight. The lymphocytes common antigen (CD45) and mast cell (MC) scores, and the number of CD3+ and CD8+ lymphocytes were higher in patients with overweight and obesity than in normal-weight subjects. Several genes involved in metabolic pathways were differently expressed in patients with overweight or obesity compared to normal weight, with upregulation of Leptin receptor and downregulation of Fatty Acid-Binding Protein 5. CONCLUSIONS: Increased BMI is associated with adipocyte and lymphocyte infiltration of the thyroid, not related to an autoimmune process, which might affect thyroid function in subjects with obesity. A differential gene expression profiling of metabolic and immune pathways in thyroid tissues of patients with obesity was also observed.

Minimally invasive video-assisted thyroidectomy: reflections after more than 2400 cases performed.

BACKGROUND: The minimally invasive video-assisted approach was developed for primary hyperparathyroidism in 1997 and the year after for thyroid disease. Since then, the technique has been adopted worldwide, and indications moved from the initial benign disease to low-risk and intermediate-risk carcinoma, demonstrating a level of oncologic radicality comparable to the conventional open approach when inclusion criteria are strictly respected. METHODS: Between 1998 and 2014, 2412 minimally invasive video-assisted thyroidectomies (MIVAT) were performed in our department. The indication for surgery in 825 patients (34.3 %) was a malignant tumor, in particular, a papillary carcinoma in 800 patients. Among them, 528 patients operated on between 2000 and 2009 had a mean complete follow-up of 7.5 (standard deviation, 2.3) years. RESULTS: A total thyroidectomy was performed in 1788 patients (74.1 %) and a hemithyroidectomy in 564 (23.4 %). Also performed was central compartment lymphadenectomy in 31 patients (1.3 %) and parathyroidectomy for the presence of a solitary parathyroid adenoma in 29 (1.2 %). Mean duration of the procedure was 41 (standard deviation, 14) minutes. After a mean follow-up of 7. 5 years, 528 patients who underwent MIVAT for low-risk or intermediate-risk papillary carcinoma presented a cure rate of 85 % (undetectable thyroglobulin), comparable with the 80 % rate reported in patients who had undergone open thyroidectomy during the same period. CONCLUSIONS: After a long experience and a considerable number of procedures performed in a single center, MIVAT is confirmed as a safe operation, with a complication rate comparable with open thyroidectomy. MIVAT offers a cure rate for the treatment of low-risk and intermediate-risk malignancies that is comparable with an open procedure when inclusion criteria are strictly respected.

High-intensity focused ultrasound as an alternative to the surgical approach in primary hyperparathyroidism: a preliminary experience.

BACKGROUND: Surgery is the therapy of choice in primary hyperparathyroidism (PHPT), although other less invasive techniques have been used in the attempt to cure the disease. Recently, high-intensity focused ultrasound (HIFU), a totally non-invasive technique, has become available to cure solid tumors. AIM: The aim of this pilot study has been to assess the safety and efficacy of HIFU in symptomatic patients with PHPT. MATERIAL AND METHODS: Four out of 31 patients with surgical indications within a cohort of 47-screened patients with PHPT were considered eligible for the study. All patients accepted to participate and were submitted to HIFU treatment in a single session. One patient was submitted to surgery after HIFU treatment. Patients were followed-up for 12 months after the procedure. RESULTS: A persistent or a partial remission of the disease, respectively, were obtained in 2 patients (50%), including the one who underwent surgery after HIFU treatment. Safety was assessed performing laryngoscopy in all patients after HIFU procedure. A transient vocal cord paralysis was observed in all patients treated by HIFU only. No permanent side effects were observed in the long term. CONCLUSIONS: HIFU might be a promising technique in treating PHPT, provided that further development of the software decreases the rate of side effects and improves the short- and long-term efficacy.

Is elastography actually useful in the presurgical selection of thyroid nodules with indeterminate cytology?

BACKGROUND: Although fine-needle aspiration cytology remains the mainstay of the preoperative workup of thyroid nodules, those with follicular proliferation still represent a diagnostic challenge. Real-time elastography (RTE) estimates the stiffness/elasticity of lesions and is regarded as a promising technique for the presurgical selection of thyroid nodules (including those with indeterminate cytology). AIM: Our aim was to verify the potential role of RTE in the presurgical diagnosis of cancer in a large cohort of consecutive patients with follicular thyroid nodules. PATIENTS AND METHODS: One hundred two patients were submitted to conventional ultrasonography and RTE evaluation before being operated on for thyroid nodule with indeterminate cytology (54% single nodules). Tissue stiffness on RTE was scored from 1 (greatest elasticity) to 4 (no elasticity). RESULTS: At conventional ultrasonography examination, the nodules (median diameter 2.2 cm) were solid (cystic areas < 10%); microcalcifications were detected in 56% of them and a hypoechoic pattern in 64%. Elasticity was high in eight cases only (score 1-2) although low in 94 (score 3-4). Cancer was diagnosed in 36 nodules (35%), being associated with microcalcifications (P < 0.0001) and inversely related to nodule diameter (P < 0.01). Malignancy was detected in 50% of the nodules with RTE score 1-2 and in 34% of those with score 3-4. Therefore, either the positive (34%) or the negative predictive value (50%) was clinically negligible. CONCLUSIONS: The current study does not confirm the recently reported usefulness of RTE in presurgical selection of nodules with indeterminate cytology and suggest the need for quantitative analytical assessment of nodule stiffness to improve RTE efficacy.

Video-assisted surgery: what is its role in the treatment of thyroid carcinoma?

Thyroid carcinoma can be divided in two main groups, differentiated, with a good prognosis and an average 10 years survival ranging from 70% to 95%, and undifferentiated which is lethal in few months. Differentiated thyroid carcinoma can be distinguished in those variants coming from follicular cells (papillary and follicular) and those from C cell (medullary carcinoma). Surgical approach represents the first step in the treatment of thyroid carcinoma. Minimally-invasive endoscopic technique can be applied only to a minority of case, the so called ''low risk'' carcinoma according to AGES and AMES criteria. During the last ten years many different endoscopic approaches have been proposed for the treatment of thyroid carcinoma and the minimally invasive videoassisted (MIVAT) by Prof Miccoli is undoubtly the one which resulted to be the most successful and spread all over the world. Through a 1.5 cm central skin incision 2 cm above the sternal notch MIVAT allows to perform a total thyroidectomy for low risk papillary carcinoma with a completeness similar to that of conventional thyroidectomy. Using the same central access it is also possible to perfom a prophylactic central neck dissection for RET gene positive carriers. A lateral neck minimally invasive videoassisted lymphadenectomy is under development for those patients with low risk papillary carcinoma and isolated lateral lymph node metastasis.

Perspectives and lessons learned after a decade of minimally invasive video-assisted thyroidectomy.

Minimally invasive video-assisted thyroidectomy (MIVAT) was introduced in our department in 1998. The procedure is based on a unique incision in the central neck, 2 cm above the sternal notch, using small conventional retractors and 2-mm reusable instruments. Hemostasis is achieved by using a Harmonic scalpel. 1,320 (1,136 female and 184 male, ratio 4:1) patients have undergone MIVAT since June 1998. Lobectomy was carried out in 421 patients, while 899 patients underwent total thyroidectomy. In 21 cases (RET oncogene mutation carriers), MIVAT was associated with central compartment lymph node clearance. Mean operative time of lobectomy was 32.3 min (range 20-120 min); for total thyroidectomy it was 44.1 min (range 30-130). Mean time for video-assisted central compartment lymphadenectomy was 57 min. Conversion to standard cervicotomy was required in 30 cases (2.2%); operative complications included transient unilateral recurrent nerve palsy in 35 cases (2.65%) and definitive unilateral recurrent nerve palsy in 15 cases (1.13%). Thirty-eight patients exhibited hypoparathyroidism, which corresponds to 4.2% of total thyroidectomies performed, but only 2 showed permanent hypoparathyroidism. MIVAT can be considered a safe operation offering significant cosmetic advantages and has possible new promising indications such as prophylactic thyroidectomy in RET gene mutation carriers.

Endoscopic bilateral neck exploration versus quick intraoperative parathormone assay (qPTHa) during endoscopic parathyroidectomy: A prospective randomized trial.

BACKGROUND: Quick intraoperative parathormone assay (qPTHa) during paratyroidectomy has become a standard procedure for patients with primary hyperparathyroidism (PHPT). This paper aims to compare endoscopic bilateral neck exploration (BE) versus focused parathyroidectomy plus qPTHa during minimally invasive video-assisted parathyroidectomy (QM). The endpoints of the study are the mean operative time and outcome of the surgical procedure (PTH and calcemia normalization at one and six months postoperatively). METHODS: Forty patients with PHPT, positive to preoperative localization studies (ultrasonography evaluation and (99)Tc-MIBI scan) for a single parathyroid adenoma, were randomly allotted into two groups. In the first group (QM), 20 patients (17 women, three men, mean age 57.6 years) underwent focused endoscopic parathyroidectomy (MIVAP tecnicque) plus qPTHa . In the second group (BE) 20 patients (17 women, three men, mean age 59.6 years) underwent endoscopic parathyroidectomy plus bilateral exploration in order to check the integrity of the remaining glands. RESULTS: There were no significant differences between groups at baseline. No conversion to cervicotomy was required. No postoperative complications were reported. The mean operative time was 32.0 vs 33.1 min [BE and QM group respectively, p = not significant (ns)]. A second macroscopically enlarged gland was removed in four patients in the BE group. Only one out of four glands was reported to be hyperplastic in the final histology. All patients were discharged on the first postoperative day. Calcemia levels were normalized in all patient of both groups, despite persistently high level of serum PTH in one patient in the QM group. CONCLUSIONS: BE can be performed endoscopically, avoiding both the time necessary for qPTHa and its cost, with the same effectiveness, but might in few cases lead to the unjustified removal of parathyroid glands slightly enlarged but not necessarily pathologic.

[New technologies in thyroid surgery. Endoscopic thyroid surgery]. / Le nuove tecnologie nella chirurgia tiroidea. Chirurgia endoscopica della tiroide.

The onset of cervicoscopy dates back to the first endoscopic parathyroidectomy in 1996. This operation, along with its several variants, has become a valid option widespread in many important centres. Later on, endoscopic or video assisted thyroidectomy was introduced in spite of the limits imposed by the mass of the gland to remove. It is indicated for a minority of patients for this reason but both parathyroidectomy and thyroidectomy showed some important advantages with respect to conventional surgery, advantages demonstrated also in prospective studies. They are mainly represented by a better cosmetic outcome and a less distressful postoperative course. These approaches proved to be safe and feasible in any surgical background: their complication rate is the same as traditional open surgery in the neck. Very promising seems to be the videoscopic access to neck lymph nodes (central and lateral compartments) whereas other fields of application such as carotid artery surgery and spine surgery still remain object of experimental studies. As far as the lateral neck dissection is concerned the technique is going to be standardized in our centre as a variant of the well known video assisted approach adding a 5 mm trocar placed in the supraclavicular space. By consequence, cervicoscopy has to be considered an important surgical tool which can be further improved but which also has an excellent potentiality.

Overall prognosis in younger patients with colorectal carcinoma.

AIM: Prognosis of colorectal cancer in younger patients is a controversial issue. While survival after curative resection seems not worse than in older patients, few data are available about the overall survival of younger patient with colorectal cancer irrespective of receiving a curative treatment or not. In this study we have reviewed our experience with patients under 45 years of age affected by colorectal cancer. METHODS: A total of 358 patients with colorectal cancer were operated on between 2001 and 2005. Nineteen patients were younger than 45. Schedules were reviewed as to palliative vs curative resection, Duke's classification, tumor grading, and compared with data from patients older than 45. RESULTS: Though no significant difference in survival can be detected after curative resection, fewer patients less than 45 years are eligible to be treated curatively. Significantly worse tumor grading and rates of curative resection make for a poorer prognosis in younger patients when compared with older ones. CONCLUSIONS: Prognosis for colorectal cancer in the overall group of patients less than 45 years is worse than in older patients. Younger patients more frequently present with distant metastases or peritoneal carcinosis which preclude the possibility of a curative treatment.

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.

Antimutagenesis studies of magnesium and calcium salts.

Magnesium is a microelement that is essential for biological functions and particularly for cellular metabolism. It has a central role in protein, lipid, carbohydrate, and nucleic acid synthesis, and it is important for muscular physiology and nerve excitability. Magnesium has an important role in the stability of biological membranes, it controls immune phenomena, and it activates over 300 enzymes. However, the mechanism of action of magnesium salts has not been well investigated and, in particular, its antimutagenesis properties and its effects in the detoxification of free radicals need further study. We investigated the effect of magnesium chloride, sulphate, carbonate, and oxide on the yeast Saccharomyces cerevisiae D7 strain, to evaluate their ability to protect against genotoxic damage. We found that magnesium salts induced antimutagenic effects in the cells harvested in the logarithmic phase by decreasing the induction of hydrogen peroxide. This, however, did not occur in the stationary phase. We also studied calcium salts of the type corresponding to those of magnesium and their protective role against the oxidative damage of free radicals and enzymatic activities, such as catalase, glutathione peroxidase, and superoxide dismutase, which are involved in antioxidative defenses.