Claudio Gambardella

Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: A retrospective study of a large clinical series

BACKGROUND In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy. METHODS The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared. RESULTS The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups. CONCLUSION In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.

Pancreatic fistula following pancreatoduodenectomy. Evaluation of different surgical approaches in the management of pancreatic stump. Literature review

Pancreatoduodenectomy is the gold standard operation for malignant and benign diseases of the pancreas and periampullary region. Even if improvements in intensive care management and surgical technique have dramatically reduced postoperative mortality after pancreatic surgery, morbidity remains high (30-50%), also in specialized pancreatic units. In order to reduce postoperative complications, particularly pancreatic fistula, different surgical techniques and their modifications have been proposed. In order to determine the better management of the pancreatic stump after pancreatoduodenectomy, the Authors analysed and compared derivative - pancreaticojejunal, pancreaticogastrostomy - vs no-derivative technique - pancreatic stump closure (duct ligation or mechanical suture, duct occlusion by fibrin glue or cyanoacrylate). A systematic research of the English literature, including major meta-analysis articles, clinical randomized trials, retrospective studies and systematic reviews was performed, analysing the risk factors and the incidence of short-medium term postoperative complications. Up to now, even if derivative procedures are preferred as gold standard the best method to deal a pancreatic stump is still controversial and remains matter of research. Pancreatic surgeons must have more than one technique for managing the pancreatic remnant.

Genetics of medullary thyroid cancer: An overview

Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib. CONCLUSIONS New genetical testings and therapeutical approaches open new perspectives in MTC management.

Germline polymorphisms of the VEGF-pathway predict recurrence in non-advanced differentiated thyroid cancer

Context: Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Objectives: Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Design: Multicenter, retrospective, observational study. Setting: Four referral centers. Patients: Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (−2578C>A, −460T>C, +405G>C, and +936C>T) and 2 VEGFR-2 (+1192 C>T and +1719 T>A) SNPs. MVD was estimated by means of CD34 staining. Outcome Measures: Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Results: Two hundred four patients with stage I–II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low- to intermediate-risk DTC (mean follow-up, 70 ± 60 months) were enrolled. Two “risk” genotypes were identified by combining VEGF-A SNPs −2578 C>A, −460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I–II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low- to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I–II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) and was slightly deleterious in low- to intermediate-risk (OR, 3.39; 95% CI, 0.8 to 14.33; P = 0.079) patients. MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Conclusions: Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC.

Bilateral benign multinodular goiter: What is the adequate surgical therapy? A review of literature

BACKGROUND Benign multinodular goiter (BMNG) is the most common endocrine disease requiring surgery. During the last few years a more aggressive approach has become the trend for bilateral BMNG treatment. METHOD Randomized clinical trials of any size that compared bilateral subtotal resection, Dunhill procedure and total thyroidectomy for benign multinodular goiter, published between January 2000 and the end of March 2015, were reviewed. DISCUSSION Total thyroidectomy can be considered the most reliable approach in preventing recurrence. The Dunhill procedure is related to a higher rate of recurrence, but rarely recurrences after Dunhill procedure lead to reoperation. Total thyroidectomy avoid completion thyroidectomy for incidental carcinoma and its related risks. Recurrent laryngeal nerve (RLN) palsy becomes less common as surgical experience increases. Transient and permanent hypoparathyroidism is strictly related to the extent of neck dissection. In the risk-cost analysis we must consider the type of patient candidated to surgery and the impact of the surgical protocol we apply. When thyroid surgery is taken in consideration, specific complication rates of different procedures in each hospital must be analyzed accordingly to patient-specific risk factors and local expertise. CONCLUSION The Dunhill procedure seems to be a good compromise between radicality and prevention of complications, avoiding reoperation for recurrence or completion thyroidectomy for incidental thyroid carcinoma. More follow-up studies and prospective studies are necessary to better evaluate, definitively, whether to prefer total thyroidectomy or Dunhill procedure in case of benign goiter surgery.

Isolated repeated anastomotic recurrence after sigmoidectomy.

Repeated anastomotic recurrence (AR) of colonic cancer is uncommon. We report a case of a double-isolated AR after sigmoidectomy. In 2003, a 60-year-old woman underwent stapled sigmoid resection for a moderately differentiated adenocarcinoma. Further rectal bleeding occurred after six months, and colonoscopy detected an AR. Thus, an additional stapled colorectal anastomosis was performed. Ten months later, a colonoscopy detected a circumferential AR that prompted the completion of a second colorectal resection, with a double-stapled colorectal anastomosis. Twenty-four hours after surgery, a massive pulmonary embolism occurred, and the patient died within a few hours. At present, only six cases of repeated isolated AR have been described. Repeated segmental colorectal resections are generally associated with a favourable prognosis, with a median survival rate of 45 mo (range, 13-132 mo). Repeated isolated ARs are rare, and segmental colorectal resections are generally associated with long-term disease-free survival.

Suprarenal solitary fibrous tumor associated with a NF1 gene mutation mimicking a kidney neoplasm: implications for surgical management.

Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm, usually occurring in the pleura. Pararenal SFT, mimicking an adrenal gland or renal tumor, as here described, is extremely rare. We report a case of a right suprarenal SFT, incidentally discovered by abdominal ultrasound in a 54-year-old woman carrying a point neurofibromatosis 1 (NF1) gene mutation. Preoperative diagnostic work-up was ineffective in evaluating its origin, and an open radical right nephrectomy was therefore undertaken. Immunohistochemical assay showed a positivity for CD34, CD99 and Bcl-2, so suggesting a diagnosis of SFT. According to our knowledge, the association between this type of tumor and NF1 gene mutation has never been described. In cases of pararenal tumors, a more detailed preoperative diagnosis could be useful to better plan the extension of resection, allowing, in selected cases, nephron-sparing surgery. More studies are needed to better analyze the relationship between NF1 gene mutation and SFT.

Leiomyosarcoma of the thyroid gland: A case report and literature review

Primary smooth muscle tumors of the thyroid gland are extremely rare neoplasms. Due to their rarity, clinical case studies concerning management are lacking. According to a literature review, only 19 cases of primary thyroid leiomyosarcomas (TLs) have been reported. In the majority of patients, the prognosis is poor since adjuvant radiochemotherapy is ineffective on local recurrence and on long-term survival. In this study, we report the case of a 77-year-old male affected by a rapidly enlarging mass of the anterior neck, associated with bilateral lung metastases, and increasing dysphagia and dyspnea during the previous 6 months. A Tir4 neoplasm fine needle cytological diagnosis of the right thyroid lobe was reached and the patient underwent total thyroidectomy (TT). Definitive histological examination identified a TL. The patient succumbed 40 days later due to respiratory distress. A literature review was performed and TL differential diagnoses, management, including alternative treatment strategies, and adjuvant therapy were analyzed. TL is an aggressive rare mesenchymal malignant tumor. Although an improved multimodal approach is often necessary, TT and neck dissection represent the treatment of choice and are often the only possible therapy. Adjuvant radiochemotherapy appears to be ineffective and a high mortality rate is observed. TL remains a fatal tumor, and innovative and more effective therapeutic strategies to improve management and outcomes are required.

Partial response to cinacalcet treatment in a patient with secondary hyperparathyroidism undergoing hemodialysis: a case report

IntroductionIn the treatment of secondary hyperparathyroidism of chronic kidney disease, calcimimetics - allosteric modulators of the calcium-sensing receptor - inhibit glandular hyperplasia and significantly reduce circulating parathyroid hormone levels. They have a major impact on the management of secondary hyperparathyroidism.Case presentationWe present the clinical case of a 41-year-old Caucasian man undergoing chronic hemodialysis, who had a parathyroidectomy to treat severe secondary hyperparathyroidism resistant to cinacalcet treatment. Preoperatively, 24 months after high-dose cinacalcet hydrochloride, we observed a persistently elevated intact parathyroid hormone serum level, and detected clear parathyroid gland hyperplasia regression on ultrasound. We performed a three-gland parathyroidectomy, which was assumed to be total, associated with a hemithyroidectomy. Our patient then entered a hypoparathyroid state. A histopathological examination showed that the removed parathyroid glands were of small size, with a total weight of 1g, associated with a multifocal small papillary thyroid cancer.ConclusionIn the management of secondary hyperparathyroidism, cinacalcet hydrochloride effectively reduces total parathyroid gland hyperplasia. However, a persisting elevated intact parathyroid hormone serum level may be observed, demonstrating that reduced parathyroid hyperplastic tissue may still be associated with severe secondary hyperparathyroidism. Even if calcimimetics are very effective in secondary hyperparathyroidism treatment, further studies are necessary for a better understanding of their actions.

Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it the surgeon who pays the bill?

BACKGROUND Thyroidectomy is one of the most common intervention in general surgery and, after the turn of the century, its rate has sharply increased, along with a worldwide increased incidence of differentiated thyroid cancers. Therefore, injuries of the recurrent laryngeal nerve have become one of the most frequent cause of surgical malpractice claims, mostly following surgery for benign pathology. MAIN BODY Even if the incidence of definitive paralysis is generally lower than 3%, during the last 20 years in Italy, the number of claims for damages has sharply raised. As a consequence, a lot of defensive medicine has been caused by this issue, and a witch-hunt has been accordingly triggered, so determining mostly a painful and lasting frustration for the surgeons, who sometimes are compelled to pay a lot of money for increasing insurance premiums and lawyers fees. Recurrent laryngeal nerve injury should be considered as a potentially catastrophic predictable but not preventable event, rather than the result of a surgical mistake. CONCLUSION Purposes of the Authors are analyzing incidence, conditions of risk, and mechanisms of recurrent laryngeal nerve injuries, underlining notes of surgical technique and defining medical practice recommendations useful to reduce the risk of malpractice lawsuits and judgments against surgeons.