A Rare Case of Negative Serum Calcitonin in Metastatic Medullary Thyroid Carcinoma: Diagnosis, Treatment, and Follow-Up Strategy.

BACKGROUND Medullary thyroid carcinoma is a rare tumor and represents less than 5% of all thyroid cancers. Tumor size and the presence of possible metastases are strictly related to serum calcitonin level, which also suggests prognosis. A serum calcitonin level above the normal range is highly suspicious for medullary cancer. This tumor has no characteristic patterns on ultrasound and fine-needle aspiration, so serum calcitonin level is the only significant element for diagnosis. The literature contains 47 cases of serum calcitonin-negative medullary thyroid cancer with heterogeneous behavior, ranging from non-aggressive to aggressive form. CASE REPORT We report a rare case of a young man with negative serum calcitonin but with lateral cervical node metastases from medullary thyroid carcinoma. At the beginning, diagnosis was not achieved due to normal range of serum calcitonin and a negative thyroid ultrasonography for large nodules. Nevertheless, in another medical center he underwent a neck biopsy of the lateral cervical mass. The histologic findings showed metastases of medullary thyroid cancer. Therefore, a total thyroidectomy plus cervical lymphadenectomy was performed. During the follow-up, due to unusefulness of serum markers, and as CEA levels were negative pre- and post-operatively, an ¹8F-DOPA PET scan was performed. In 3 years of follow-up, there is still no evidence of disease relapse. CONCLUSIONS Our case shows how a normal serum level of calcitonin cannot exclude medullary thyroid cancer. Early diagnosis is crucial because it influences appropriate surgical therapy and patient outcome. The current lack of an optimal strategy for the diagnosis and postoperative follow-up for patients with negative serum calcitonin tumor presents a diagnostic challenge for physicians.

[Treatment of microcarcinoma and papillary carcinoma of the thyroid]. / Trattamento del microcarcinoma e del carcinoma papillifero della tiroide.

AIM OF THE STUDY: Of our is to demonstrate that total thyroidectomy with lymphadenectomy of the six level is effective in papillary thyroid carcinomas than for microcarcinoma, according to recent acquisitions on the biological behavior of some microcarcinoma. MATERIALS AND METHODS: Ours is a retrospective study based on analysis of the process of therapy in 2849 patients undergoing total thyroidectomy, performed from January 1985 to January 2008 by our group at the U.O. Clinica Chirurgica Ospedale "Vittorio Emanuele" of Catania, Italy. RESULTS: Of all the interventions of total thyroidectomy, 75% performed for benign disease and 25% for malignant disease (PTMC 356 cases, 291 PTC cases, 56 cases of follicular carcinoma, 5 cases of medullary carcinoma, anaplastic carcinoma, 2 cases). 40% of PTMC underwent TT and subsequent follow up, because the diagnosis was placed postoperatively and in 60% diagnosis was placed during surgery with indication for TT and lymphadenectomy of the sixth level and subsequent follow-up showed no evidence of residual disease or relapse. PTC of 40% underwent a TT with lymphadenectomy of the sixth level. 60% of patients with PTC underwent a TT with lymphadenectomy of the sixth level and lateral cervical lymphadenectomy was performed only in 3 cases with a TT level VI lymphadenectomy of the bilateral lateral cervical lymphadenectomy. All patients in the follow-up post-operatively does not show in the following years, signs of residual disease or relapse. CONCLUDING REMARKS: From the results we can confirm that a total thyroidectomy with lymphadenectomy of the sixth level, the more lateral lymphadenectomy of the neck when needed, ensures a good prognosis and few complications, if ever performed in expert hands. This applies to papillary carcinomas than for microcarcinoma whose surgical treatment (total thyroidectomy, lobectomy, subtotal thyroidectomy or near-total) is still debated.

[Total thyroidectomy vs subtotal thyroidectomy for plurinodular goiter. Analysis 1517 cases]. / L'efficacia della tiroidectomia totale nel gozzo plurinodulare. Un'esperienza di 1517 casi.

AIM OF THE STUDY: The surgical treatment of benign thyroid diseases is still controversial, as there is a tendency by some Authors toward a more conservative treatments and wider treatments by others. OBJECTIVE: To claim and demonstrate that total thyroidectomy is the best and effective surgical therapy in benign thyroid diseases. MATERIALS AND METHODS: Retrospective study based on an analysis of 2136 patients with benign thyroid diseases of the thyroid, observed from January 1985 to July 2008 in the Operative Unit of Surgical Clinic of the Ospedale Vittorio Emanuele of Catania. Patients with certain or suspected diagnosis of thyroid cancer have been drawn out from the study. RESULTS: 71% of the patient (that is 1517) were treated for a goiter, 5.9% with preoperative diagnosis of recurrent goiter; 105 cases of primary and non recurrent goiter (6.9%) were found to have foci of microcarcinoma (PTMC) at final histologic examination. All cases of recurrent goiter were selected as non responders patients to suppressive therapy. Total thyroidectomy was performed on 1183 cases (78%), including 89 that required the totalizations for recurrent goiter. The remaining 334 cases with a diagnosis of multinodular goiter were treated with lobectomies or near-total and subtotal thyroidectomy because the remaining parenchima showed macro- and microscopically free of disease. In 1094 cases a total thyroidectomy was performed because extemporary histological examination showed architectural and cytological abnormalities considered as indicative of the formation of new nodules. CONCLUDING REMARKS: The histological examination carried out on portions of macroscopically healthy thyroid showed almost ubiquitous spread of the disease in the gland, with marks of presumable evolutive disease. Moreover has been also documented the not negligible possibility that residual parenchyma may undergo malignant degeneration. These two last observations justify our inclination toward a radical treatment also of benign thyroid diseases.

[Parathyroid cyst. Case report]. / Cisti paratiroidea. Caso clinico.

Parathyroid cysts (PCS) are rare, and less than 300 cases have been reported in literature till now. They occur in most cases as a swelling at the lower third of the neck or are identified by means of diagnostic tests performed for other neck diseases. They are rarely symptomatic. They are often confused with thyroid nodules. Rarely give compressive symptoms. PCS are divided into functional (causing hyperparathyroidism, hypercalcemia and hypophosphatemia) and not functional PCS that represent about 10% of PCS. The non functional PCS are considereted true PCS because their wall is lined by secretory epithelium, instead of the functioning ones that are cystic degeneration of parathyroid gland adenomas. The histopathological data suggest the origin of two different variants of PCS. Their diagnosis requires knowledge of the disease and an high suspicion for it. Ultrasound associated with FNA is the first instance investigation. The ultrasound study allows to verify the nature of the cystic lesion and its peripheral vasculature, whereas FNA can observe the macroscopic characteristics of the liquid sample (clear liquid called "water from rocks") and to dose the levels of PTH and C-terminal/mid-region of PTH itself. The dose of intracystc PTH is the universally accepted method for diagnosis of PCS. The first treatment is the aspiration FNA, which can be curative, but recurrences can be treated surgically. Here is a case of PCS, which we observed in June 2009.

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview.

Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A "liquid biopsy" is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer.

Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence.

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.

[New trends in the treatment of venous leg ulcer. Personal experience]. / Recenti acquisizioni sul trattamento delle ulcere flebostatiche degli arti inferiori. Nostra esperienza.

Venous leg ulcer is the most frequent cause of trophic lesions of the limbs in patients with chronic venous insufficiency. Appropriate management of cutaneous vascular lesions is based on systemic, vascular and local assessment. The Authors used a protease-modulating matrix in 126 patients suffering from venous leg ulcers with wound granulation: 81 (64.2%) patients with primary chronic reflux disorder and varicose veins and 45 (35.8%) post-thrombotic; in addition 30 patients (23.8%) had peripheral arteriopaty and 41 (32.5%) peripheral arteriopaty and diabetes. One hundred sixteen patients showed complete healing, 2 were refractory to every treatment and 8, with arteriopathy and diabetes, are on the mend. According to the literature we achieved reduction of the healing time and increased healing rate. All patients were treated in outpatient settings. In conclusion the Authors suggest protease-modulating matrix is a really effective treatment of venous leg ulcers with wound granulation. Their treatment is also feasible in outpatient treatment with a reduction in health spending and reduced absence from work.

[Pelvic splenomegaly. Ptosic, migrant or accessory spleen?]. / Splenomegalia in sede pelvica. Milza ptosica, migrante o accessoria?

A wandering or ectopic spleen is a rare condition in which the spleen is not located in the left upper quadrant but is found lower in the abdomen or in the pelvic region caused by improper fixation of the ligamentous attachments. Laxity of the peritoneal attachments of the spleen results in splenic hyper mobility, known as wandering spleen. Congenital and acquired causes have been advocated to explain its onset. However, the precise aetiology is not completely understood. Many patients with wandering spleen are asymptomatic and therefore, the real incidence is unknown. Symptomatic patients may have intermittent abdominal pain because of splenic congestion with intermittent torsion of the splenic pedicle and its spontaneous detorsion, or may present acutely with pedicle torsion with subsequent infarction. Pain and dangerous potential evolution recommend surgery, splenoplexy or splenectomy. The Authors report the case of a 48-year-old man with painful abdominal mass suspected for wandering splenomegaly after diagnostic imaging (abdominal Ultrasonography and TC). Laparotomy evidenced a large spleen (DL 22 cm.) with a long (1 mt) and tortuous vascular pedicle, both removed. Histopathologic examination showed partial infarction of the spleen. The postoperative course was uneventful.

[Benign phylloides tumor of the breast. Considerations on a clinical case]. / Tumore fillode gigante benigno della mammella. Considerazioni a proposito di un caso clinico.

Phyllodes tumors are unusual biphasic fibroepithelial neoplasms of the breast, accounting for < 1% of all breast tumors and raising issues of diagnosis and therapeutic choice. They can grow quickly and when the maximum diameter is greater than 10 cm. We talk about giant phyllodes tumors. Ultrasound, Mammography and FNA are not effective. A potentially useful diagnostic modality is MRI. Core tissue biopsy or incisional biopsy represent the preferred means of pre-operative diagnosis. Conservative treatment can be effective also in giant tumors depending upon the size of the tumor and the breast if a complete excision with an adequate margin of normal breast tissue can be achieved, so avoiding local recurrence often accompanied by worse histopathology. The Authors report the case of a giant benign phyllode tumor of the breast treated with conservative surgery, quadrantectomy and oncoplasty. No local recurrence at 4 years follow-up.

Hypothyroidism as a Predictor of Surgical Outcomes in the Elderly.

There is a high prevalence of hypothyroidism in the elderly population, mainly among women. The most important cause is autoimmune thyroiditis, but also iodine deficiency, radioiodine ablation, and surgery may be responsible for hypothyroidism in elderly hospitalized patients. Thyroid-related symptoms are sometimes comparable to physiological manifestations of the aging process, and hypothyroidism may be related with many symptoms which can be present in critical patients, such as cognitive impairment, cardiovascular, gastrointestinal, and hematological alterations, and eventually myxedema coma which is a severe and life-threatening condition in older adults. Adequate thyroid hormone levels are required to achieve optimal outcomes from any kind of surgical intervention. However, only few randomized clinical trials investigated the association between non-thyroidal illness (or low-T3 syndrome), and adverse surgical outcomes, so far. The goal of this review is to discuss the role of thyroid function as a predictor of surgical outcomes in the elderly.

DDR1 regulates thyroid cancer cell differentiation via IGF-2/IR-A autocrine signaling loop.

Patients with thyroid cancers refractory to radioiodine (RAI) treatment show a limited response to various therapeutic options and a low survival rate. The recent use of multikinase inhibitors has also met limited success. An alternative approach relies on drugs that induce cell differentiation, as the ensuing increased expression of the cotransporter for sodium and iodine (NIS) may partially restore sensitivity to radioiodine. The inhibition of the ERK1/2 pathway has shown some efficacy in this context. Aggressive thyroid tumors overexpress the isoform-A of the insulin receptor (IR-A) and its ligand IGF-2; this IGF-2/IR-A loop is associated with de-differentiation and stem-like phenotype, resembling RAI-refractory tumors. Importantly, IR-A has been shown to be positively modulated by the non-integrin collagen receptor DDR1 in human breast cancer. Using undifferentiated human thyroid cancer cells, we now evaluated the effects of DDR1 on IGF-2/IR-A loop and on markers of cell differentiation and stemness. DDR1 silencing or downregulation caused significant reduction of IR-A and IGF-2 expression, and concomitant increased levels of differentiation markers (NIS, Tg, TSH, TPO). Conversely, markers of epithelial-to-mesenchymal transition (Vimentin, Snail-2, Zeb1, Zeb2 and N-Cadherin) and stemness (OCT-4, SOX-2, ABCG2 and Nanog) decreased. These effects were collagen independent. In contrast, overexpression of either DDR1 or its kinase-inactive variant K618A DDR1-induced changes suggestive of less differentiated and stem-like phenotype. Collagen stimulation was uneffective. In conclusion, in poorly differentiated thyroid cancer, DDR1 silencing or downregulation blocks the IGF-2/IR-A autocrine loop and induces cellular differentiation. These results may open novel therapeutic approaches for thyroid cancer.

Adrenalectomy for incidentaloma: lessons learned from a single-centre series of 274 patients.

BACKGROUND: Adrenal incidentalomas are increasingly diagnosed and include a wide spectrum of lesions from benign adenomas to secreting or malignant lesions. The aim of the present study is to report a large single-institution experience of patients undergoing surgery for adrenal incidentaloma with particular attention to their diagnosis and post-operative course and the evolution of surgical practice over time. METHODS: From 1993 to 2013, 274 patients underwent adrenalectomy for incidentaloma. All patients underwent standardized clinical, hormonal and imaging assessments. RESULTS: Patients were mainly female (63.1%; n = 173), and the median age of patients was 56.5 years. After a complete hormonal evaluation, 47.9% (n = 129) of incidentalomas were classified as secreting tumours, including 24.4% (n = 67) subclinical cortisol-secreting adenomas and 18.9% (n = 52) pheochromocytomas. Adrenocortical carcinomas represented 9.5% (n = 26) of incidentalomas, and the risk of malignancy was significantly correlated with tumour size. The conversion rate after laparoscopic adrenalectomy (90.9%; n = 249) was 3.2% (n = 8). The overall morbidity rate was 13.9%, which included a 4.4% rate of severe morbidity (Clavien-Dindo ≥3). From 2008 onwards, there was a significant decrease (P < 0.001) in the use of surgical approaches for non-secreting adenomas. CONCLUSION: After a complete work-up, half of the incidentalomas were classified as subclinical oversecreting adrenal lesions and 10% proved to be malignant adrenocortical carcinomas. The debatable use of surgical approaches for benign nonfunctioning adenomas significantly decreased over time.

Nutritional aspects in patient undergoing liver resection.

In the past two decades, hepatic surgery has achieved important technical breakthroughs resulting in a drastic reduction of the onset of complications and in an improved post-resective survival. Pre-operative nutritional status is one of the key points for the success of a liver resection. Modern surgical achievement such as the development of living-related liver donation, and the possibility to perform more laparoscopic liver resection gave us the opportunity to extend post-operative protocol focused on early intestinal feeding to tumor patients. The aims of this review were to report the current status of the knowledge regarding nutritional aspects in liver resection patients.