GJB5 association with BRAF mutation and survival in cutaneous malignant melanoma.

BACKGROUND: Gap-junctional intercellular communication is crucial for epidermal cellular homeostasis. Inability to establish melanocyte-keratinocyte contact and loss of the intercellular junction's integrity may contribute to melanoma development. Connexins, laminins and desmocollins have been implicated in the control of melanoma growth, where their reduced expression has been reported in metastatic lesions. OBJECTIVES: The aim of this study was to investigate connexin 31·1 (GJB5) expression and identify any association with BRAF mutational status, prognosis of patients with melanoma and mitogen-activated protein kinase (MAPK) inhibitor (MAPKi) treatment. METHODS: GJB5 expression was measured at RNA and protein level in melanoma clinical samples and established cell lines treated (or not) with BRAF and MEK inhibitors (MEKi), as well as in cell lines which developed MAPKi resistance. Findings were further validated and confirmed by analysis of independent datasets. RESULTS: Our analysis reveals significant downregulation of GJB5 expression in metastatic melanoma lesions compared with primary ones and in BRAF-mutated vs. BRAF-wildtype (BRAFWT ) melanomas. Likewise, GJB5 expression is significantly lower in BRAFV600E compared with BRAFWT cell lines and increases on MAPKi treatment. MAPKi-resistant melanoma cells display a similar expression pattern compared with BRAFWT cells, with increased GJB5 expression associated with morphological changes. Enhancement of BRAFV600E expression in BRAFWT melanoma cells significantly upregulates miR-335-5p expression with consequent downregulation of GJB5, one of its targets. Furthermore, overexpression of miR-335-5p in two BRAFWT cell lines confirms specific GJB5 protein downregulation. Reverse transcriptase quantitative polymerase chain reaction analysis also revealed upregulation of miR-335 in BRAFV600E melanoma cells, which is significantly downregulated in cells resistant to MEKi. Our data were further validated using the TCGA_SKCM dataset, where BRAF mutations associate with increased miR-335 expression and inversely correlate with GJB5 expression. In clinical samples, GJB5 underexpression is also associated with patient overall worse survival, especially at early stages. CONCLUSIONS: We identified a significant association between metastases/BRAF mutation and low GJB5 expression in melanoma. Our results identify a novel mechanism of gap-junctional protein regulation, suggesting a prognostic role for GJB5 in cutaneous melanoma.

Fascia-iliaca compartment block vs intra-articular hip injection for preoperative pain management in intracapsular hip fractures: A blind, randomized, controlled trial.

BACKGROUND: The aim of this study was to compare the fascia-iliaca compartment block and the intra-articular hip injection in terms of pain management and the need for additional systemic analgesia in the preoperative phase of intracapsular hip fractures. METHODS: Patients >65 years old with an intracapsular hip fracture were randomized in this prospective, blind, controlled, parallel trial in a Level-I trauma center. Patients were randomly assigned to receive either the fascia-iliaca compartment block (cohort FICB) or the intra-articular hip injection (cohort IAHI) upon admission to the emergency department. The primary outcome was pain relief at 20 min, 12 h, 24 h and 48 h after the regional anesthesia, both at rest and during internal rotation of the fractured limb. The Numeric Rating Scale was used. Residual pain was managed with the same protocol in all patients. Additional analgesic drug administration during the 48 h from admission was recorded. RESULTS: A total of 120 patients with comparable baseline characteristics were analyzed in this study: the FICB group consisted of 70 subjects, while the IAHI group consisted of 50 subjects. Pain was significantly lower in the IAHI group during movement of the fractured limb at 20 min (p < 0.05), 12 h (p < 0.05), 24 h (p < 0.05) and 48 h (p < 0.05). In the FICB cohort 72.9% of patients needed to take oxycodone, in contrast to 28.6% of the IAHI cohort (p < 0.05). In the FICB cohort 14.09 ± 11.57 mg of oxycodone was administered, while in the IAHI cohort 4.38 ± 7.63 mg (p < 0.05). No adverse events related to either technique were recorded. CONCLUSIONS: Intra-articular hip injection provides better pre-operatory pain management in elder patients with intracapsular hip fractures compared to the fascia-iliaca compartment block. It also reduced the need for supplementary systemic analgesia. LEVEL OF EVIDENCE: Therapeutic Level I.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

Solitary thyroid metastasis from colon cancer: a rare case report.

Malignant metastases to the thyroid are rare and are even rarer from a colorectal primary. As these metastases are often asymptomatic, they are usually discovered incidentally on imaging performed as follow-up for the primary tumour. In this report, we present a case of metastatic sigmoid adenocarcinoma to the thyroid diagnosed and treated at our institution.

Does lesser trochanter implication affect hip flexion strength in proximal femur fracture?

PURPOSE: In pertrochanteric and intertrochanteric femoral fractures, the avulsion of the lesser trochanter by the pull of the iliopsoas muscle is not uncommon. This fragment is not commonly fixed because the avulsion of the lesser is tough to not influence the clinical outcome but up to date there is no evidence to support this statement. The aim of this study is to evaluate if lesser trochanter implication affects psoas muscle strength in proximal femur fracture. MATERIALS AND METHODS: Patients with a consolidated intertrochanteric or pertrochanteric fracture associated or not with lesser trochanter fracture were enrolled, respectively, in group A and group B. Criteria of inclusion were the achievement of an anatomic reduction with gamma nail and a complete consolidation of the fracture. Criteria of exclusion were a follow-up shorter than 6 months and age over 65 years old at surgery. Patients were retrospectively reviewed for the purpose of this study. Range of motion, modified Harris Hip Score (mHHS), flexion strength with hip in neutral position, at 90° of flexion and in "figure four" position were evaluated on injured and healthy side. On the pre-operative X-rays, the vertical displacement of the lesser trochanter was calculated. RESULTS: Groups A and B showed no significant difference in age and follow-up. No statistical difference between the two groups was found in range of motion, mean mHHS, hip flexion strength at 90° of hip flexion. Lesser trochanter fracture group showed a significantly reduced strength in flexion with hip in neutral flexion (mean difference between two groups was 18.5 kgf). Lesser trochanter displacement showed a significant correlation with strength at 90° of flexion. CONCLUSIONS: Our results showed that lesser trochanter implication may result in decreased hip flexion strength. Lesser trochanter displacement is directly correlated with flexion strength. Further studies will be necessary to understand if lesser trochanter fixation may be a good solution for those patients.

Motor and functional recovery after neck dissection: comparison of two early physical rehabilitation programmes.

The aim of this prospective, single-centre, non-randomized explorative study is to comparatively assess two-month results of two early rehabilitation programmes in patients receiving neck dissection for head and neck cancer, with the hypothesis that those not receiving therapist-assisted physiotherapy would take an active role in their own rehabilitation to enhance outcomes. At the European Institute of Oncology, Milan (Italy), 97 patients were registered during the pre-hospitalization period and divided into an Autonomous group (living distant from the hospital) and a Physio group (living near). As expected, only 50 patients (25 per group) completed the study. Both groups received a Physical Therapy Brochure with instructions on to how to perform exercises at home. Home physical exercises started five days after surgery and continued for two months. The Autonomous group received a pre-surgery instruction session; the Physio group attended four once-weekly therapist-guided physiotherapy sessions. Two months after surgery, arm mobility and pain had recovered to pre-operative levels. Most endpoints, including the main composite, did not differ between groups. Although longer-follow-up is necessary, early physiotherapy seems to be effective in maintaining arm mobility and reducing pain, even in patients empowered to do exercises autonomously.

Central neck dissection in differentiated thyroid cancer: technical notes.

Differentiated thyroid cancers may be associated with regional lymph node metastases in 20-50% of cases. The central compartment (VIupper VII levels) is considered to be the first echelon of nodal metastases in all differentiated thyroid carcinomas. The indication for central neck dissection is still debated especially in patients with cN0 disease. For some authors, central neck dissection is recommended for lymph nodes that are suspect preoperatively (either clinically or with ultrasound) and/or for lymph node metastases detected intra-operatively with a positive frozen section. In need of a better definition, we divided the dissection in four different areas to map localization of metastases. In this study, we present the rationale for central neck dissection in the management of differentiated thyroid carcinoma, providing some anatomical reflections on surgical technique, oncological considerations and analysis of complications. Central neck dissection may be limited to the compartments that describe a predictable territory of regional recurrences in order to reduce associated morbidities.

Erythrocyte glutathione transferase: a non-antibody biomarker for systemic sclerosis, which correlates with severity and activity of the disease.

Erythrocyte glutathione transferase (e-GST) is a detoxifying enzyme hyper-expressed in nephropathic patients and used recently as a biomarker for blood toxicity. Systemic sclerosis (SSc) is characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Renal involvement is frequent in SSc patients. Here we show that e-GST is hyper-expressed in SSc patients (n = 102) and correlates (R(2) = 0.49, P < 0.0001) with the Medsger DSS and DAI Valentini indices that quantify the severity and activity of this disease. Interestingly, e-GST does not correlate with the impairment of kidney or other specific organs taken separately. e-GST hyper-expression seems to be linked to the presence of a factor (i.e., toxin) that triggers the autoimmune disease, and not to the damage of specific organs or to oxidative stress. e-GST may be proposed as an innovative non-antibody biomarker for SSc useful to check the progress of this disease and the efficiency of new therapeutic strategies.

Metastasis to the right stellate ganglion and vagal nerve: pathological alterations causing sudden death. A case report.

Sudden death in a 66-year-old woman with squamous cell carcinoma of the oral cavity and exclusive metastatic involvement of the right stellate ganglion and right nerve vagus is reported. The patient also suffered from paroxysmal atrial fibrillation treated with quinidine. An autopsy showed exclusive metastases to the right stellate ganglion and vagus nerve, along with decreased nerve fibre density in the ventricular myocardium suggesting that Wallerian axon degeneration of cardiac fibres was responsible for sudden death.

Platelet vitamin D receptor is reduced in osteoporotic patients.

AIM: It is well known that vitamin D plays an important role in maintaining bone homeostasis and in regulating calcium absorption. The active form of vitamin D interacts with its receptor the VDR that is expressed in multiple tissues and it is involved in platelets (PLTs) function. In the present study we evaluate PLTs' VDR expression in osteoporotic as opposed to healthy subjects. METHODS: We enrolled in the study 77 women with postmenopausal osteoporosis, 33 healthy women of childbearing age, 49 healthy men, and 11 healthy women matched with patients for age and postmenopausal period. Thirty-nine patients had had one femoral fracture occurred after the age of fifty and attributable to primary osteoporosis. Bone mineral density, markers of bone metabolism and VDR levels were measured in all the subjects. RESULTS: Our data show that VDR level is lower in patients as respect to controls and is positively correlated with bone density, but not with markers of bone metabolism. We also found a decrease in the phosphorus levels in patients without differences in vitamin D levels and in the dietary calcium intake. CONCLUSION: The lower VDR expression in osteoporotic could indicate a lower ability to respond to vitamin D, and could be the explanation of the increase in the PTH and decrease in the phosphorus levels in patients with respect to controls.

Targeting of the adaptor protein Tab2 as a novel approach to revert tamoxifen resistance in breast cancer cells.

Pharmacological resistance is a serious threat to the clinical success of hormone therapy for breast cancer. The antiproliferative response to antagonistic drugs such as tamoxifen (Tam) critically depends on the recruitment of NCoR/SMRT corepressors to estrogen receptor alpha (ERα) bound to estrogen target genes. Under certain circumstances, as demonstrated in the case of interleukin-1ß (IL-1ß) treatment, the protein Tab2 interacts with ERα/NCoR and causes dismissal of NCoR from these genes, leading to loss of the antiproliferative response. In Tam-resistant (TamR) ER-positive breast cancer cells, we observed that Tab2 presents a shift in mobility on sodium dodecyl sulfate--PAGE (SDS-PAGE) similar to that seen in MCF7 wt upon stimulation with IL-1ß, suggesting constitutive activation. Accordingly, TamR treatment with Tab2-specific short interfering RNA, restored the antiproliferative response to Tam in these cells. As Tab2 is known to directly interact with the N-terminal domain of ERα, we synthesized a peptide composed of a 14-aa motif of this domain, which effectively competes with ERα/Tab2 interaction in pull-down and co-immunoprecipitation experiments, fused to the carrier TAT peptide to allow internalization. Treatment of TamR cells with this peptide resulted in partial recovery of the antiproliferative response to Tam, suggesting a strategy to revert pharmacological resistance in breast cancer. Silencing of Tab2 in TamR cells by siRNA caused modulation of a gene set related to the control of cell cycle and extensively connected to BRCA1 in a functional network. These genes were able to discern two groups of patients, from a published data set of Tam-treated breast cancer profiles, with significantly different disease-free survival. Altogether, our data implicate Tab2 as a mediator of resistance to endocrine therapy and as a potential new target to reverse pharmacological resistance and potentiate antiestrogen action.

A Decision Support System for the assisted diagnosis of brain tumors: a feasibility study for ¹8F-FDG PET preclinical studies.

Decision support systems for the assisted medical diagnosis offer the main feature of giving assessments which are poorly affected from arbitrary clinical reasoning. Aim of this work was to assess the feasibility of a decision support system for the assisted diagnosis of brain cancer, such approach presenting potential for early diagnosis of tumors and for the classification of the degree of the disease progression. For this purpose, a supervised learning algorithm combined with a pattern recognition method was developed and cross-validated in ¹8F-FDG PET studies of a model of a brain tumour implantation.

Ultrasound dye-assisted surgery (USDAS): a promising diagnostic and therapeutic tool for the treatment of cancer recurrences in the neck.

The evolution of new techniques for cancer surgery has led to important changes in cancer care in recent years. The endpoint of cancer treatment is now to treat the patient with minimum discomfort while respecting quality of life. New techniques, such as mini-invasive surgery, must respect the correct oncological indications, when technically feasible. The surgery for nodal spread or recurrence of disease, after previous surgery on T or T and N for neck cancer, can represent a diagnostic and therapeutic challenge, especially in the neck, which is characterized by small spaces and noble structures. Often lesions become enveloped in scar tissue and can be difficult to visualize during surgery, representing a genuine problem for the surgeon. Ultrasound dye-assisted surgery is a procedure that combines ultra-sound localization of pathological nodes with the use of methylene blue to mark diseased structures to simplify their visualization (and thus removal) in the surgical field. The technique is simple and can be used in surgically and oncologically experienced hands, even in hospitals that do not have sophisticated technology.

Identification of patients at high risk for hypocalcemia after total thyroidectomy.

Hypocalcemia is a major post-operative complication of total thyroidectomy, causing severe symptoms and increasing hospitalization time. The primary cause is secondary hypo-parathyroidism following damage to, or devascularisation of, one or more parathyroid glands during surgery. Aim of the study was to develop a simple and reliable method for predicting post-operative hypocalcemia in total thyroidectomy patients. A retrospective analysis was made of immediate pre-operative and early post-operative calcium levels in 100 patients. It was found that a marked decrease in blood calcium, immediately after surgery, was a sensitive predictor of hypocalcemia. In a subsequent prospective series of 67 patients, the efficacy was assessed of early administration of calcium plus Vitamin D in reducing symptomatic hypocalcemia in patients in whom the difference (Δ) between pre- and post-operative blood calcium was ≥ 1.1 mg/dl. This treatment was part of a protocol in which normo-calcemic patients were discharged immediately after drainage removal (third post-operative day). In the retrospective series, 84% of patients who developed hypocalcemia had Δ ≥ 1.1 and 54% of patients who did not develop hypocalcemia had Δ < 1.1 (p < 0.0001). Mean duration of hospitalization was 6.2 days. In the prospective series, 76% of patients who developed hypocalcemia had Δ ≥ 1.1 mg/dl; of the patients who did not develop hypocalcemia 75% had Δ < 1.1 mg/dl (p = 0.0013); mean hospitalization was 4.7 days (p < 0.0001). Use of the 1.1 mg/dl cut-off for deciding whether to start early prophylaxis allowed most patients to avoid symptomatic hypocalcemia (and the associated anxiety), while permitting a significantly reduced hospital stay, resulting in lower hospitalization costs.

Genotype, phenotype and hormonal levels correlation in non-classical congenital adrenal hyperplasia.

Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition sustained by the reduced function of one of the enzymes involved in the adrenal steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of enzyme activity impairment determine different clinical pictures, with childhood or post-pubertal onset. The aim of this study was to evaluate the relationship between genotype, phenotype, and adrenal hormonal levels in a group of 66 patients affected by NCAH attending outpatient pediatric or endocrinological Clinics. Our findings show that age at pubarche/menarche was significantly younger, height SD score) and Δ bone age-chronological age were significantly higher in patients with a more severe enzyme activity impairment, while cutaneous androgenization and menstrual irregularities in post-pubertal girls were not related to the grading of genotype.

Phenotype of five cases of prenatally diagnosed campomelic dysplasia harboring novel mutations of the SOX9 gene.

OBJECTIVES: Campomelic dysplasia is a rare congenital skeletal disorder characterized by bowing of the long bones and a variety of other skeletal and extraskeletal defects, many of which can now be identified prenatally using advanced ultrasound equipment. The disorder is caused by mutations in SRY-box 9 (SOX9), a gene that is abundantly expressed in chondrocytes as well as in other tissues. However, the correlation between genotype and phenotype is still unclear. We report five cases of prenatally detected campomelic dysplasia in which the diagnosis was confirmed by molecular analysis. METHODS: Ultrasound examinations were performed between 12 and 32 weeks. Standard fetal biometric measurements were obtained. Fetal sex was determined sonographically and confirmed by chromosomal analysis. Genomic DNA was obtained in four cases before termination of pregnancy from chorionic villi or amniocytes and in one case postnatally from peripheral blood. RESULTS: Skeletal dysplasia, most often limb shortening and bowed femora, was observed in one case in the first trimester, in three cases in the second trimester and in one case, presenting late for antenatal care, in the third trimester. Four of the pregnancies were terminated and one was carried to term. Postmortem/postnatal physical and radiographic examinations confirmed the presence of anomalies characteristic of campomelic dysplasia. A de novo mutation in the SOX9 gene was detected in all four cases that underwent termination. The father of the proband in the case that went to term was a carrier of a somatic mosaic mutation without clinical or radiographic signs of campomelic dysplasia. CONCLUSIONS: It is likely that the integrated expertise of ultrasonographers, obstetricians, pediatricians and clinical geneticists will markedly improve the likelihood of accurate prenatal clinical diagnoses of campomelic dysplasia. This will, in turn, encourage more specific molecular testing and facilitate comprehensive genetic counseling.

Laser surgery of early glottic cancer in elderly.

Aim of this retrospective study is to evaluate the impact of transoral laser surgery of early glottic cancer in elderly patients in terms of feasibility, disease-free survival, overall survival and organ preservation, in a single Institute (European Institute of Oncology). A total of 122 patients (male/female ratio 113/9), over 70s with untreated early stage glottic cancer, were consecutively evaluated and treated at the European Institute of Oncology from 2000 to 2008. None had contraindications to general anaesthesia and all patients signed informed consent to this surgical treatment. The severity of pre-operative comorbidities and the intra-operative risk were evaluated according to the American Society of Anaesthesiologists Grading classification. All patients underwent laser cordectomies according to the European Laryngological Society classification. Histopathological examination demonstrated no evidence of tumour (pT0) in 19 patients (calculated only in patients with a previous vocal cord biopsy positive for squamous cell carcinoma), pTis in 18, pT1a in 53, pT1b in 16, pT2 in 14 and pT3 in 2, respectively. A 10-year overall survival, a tumour specific survival and a laryngeal tumour-specific survival were, respectively, 64.9%, 84.8% and 94.3%. In conclusion, transoral laser surgery is feasible in elderly patients with early stage glottic cancer, providing good results in terms of disease-free survival, organ preservation and quality of life. Our group of elderly patients had no intra-operative or post-surgical complications and resumed normal activities the day after discharge from hospital. Considering these factors, we can assess, that transoral laser surgery, therefore, represents a modern treatment that should be offered as an alternative to conventional radiotherapy in elderly patients with early glottic cancer referred to medical centres with expertise for this surgical procedure.

A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations.

BACKGROUND AND PURPOSE: Duplications of lamin B1 (LMNB1) at 5q23 are implicated in adult-onset autosomal dominant leukodystrophy (ADLD) having been described in six families with diverse ethnic background but with a homogeneous phenotype. In a large Italian family, we recently identified a variant form of ADLD characterized clinically by absence of the autonomic dysfunction at onset described in ADLD and, on MRI, by milder cerebellar involvement with sparing of hemispheric white matter. Aim of this study was to investigate the genetic basis of this variant form of ADLD. METHODS: We carried out a genome-wide linkage analysis using microsatellite markers, and the genes in the candidate region were screened for point mutations. LMNB1 was also screened for deletions/duplications by real-time PCR, multiplex ligation-dependent probe amplification and Southern blot. RESULTS: We mapped the variant ADLD locus to 5q23.2-q23.3, a genomic region containing 11 genes including LMNB1. Neither gene copy-number defects nor point mutations in the LMNB1 gene were found. We also excluded point mutations in the coding exons of the other ten genes in the candidate region. However, expression of lamin B1 evaluated in lymphoblastoid cells was higher in patients than in healthy controls, and was similar to the lamin B1 expression levels found in a patient with LMNB1 duplication. CONCLUSIONS: This observation suggests that a mutation in an LMNB1 regulatory sequence underlies the variant ADLD phenotype. Thus, adult forms of ADLD linked to 5q23 appear to be more heterogeneous clinically and genetically than previously thought.

In vitro and in vivo phase II metabolism of combretastatin A-4: evidence for the formation of a sulphate conjugate metabolite.

1. Combretastatin A-4 (CA-4), is a natural compound with a potent tubulin polymerization and cell growth inhibitor properties. For these reasons CA-4 is one of the most potent anti-vascular agents that shows strong cytotoxicity against a variety of human cancer cells, including multi-drug-resistant cancer cell lines. In order to complete the knowledge of metabolic fate of CA-4, the in vitro and in vivo phase II metabolism was investigated. 2. Both in incubation with rat and human liver S9 preparation in the presence of 39-phosphoadenosine-5 -phosphosulfate (PAPS) as a cofactor the formation of a previously no reported sulphate metabolite was demonstrated through liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) data and comparison with a synthetic reference sample. 3. In incubation of CA-4 using rat and human liver microsomes, the formation of CA-4 glucuronide was observed and chromatographic and mass spectral properties of the metabolite were achieved and compared with those of a synthetic reference sample. 4. Incubation of CA-4 with rat and human liver S9 preparation in the presence of uridine-5 -diphosphoglucuronic acid trisodium salt (UDPGA) and an beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-regenerating system as cofactors resulted in the formation of glucuronides arising from phase I CA-4 metabolites. 5. When CA-4 was administered intraperitoneally to rat at a dose of 30 mg kg(-1), both glucuronide and sulphate metabolites were observed in LC-ESI-MS-MS chromatograms and their mass spectral data were identical to those obtained from synthetic standards.

Role of prophylactic central neck dissection in cN0 papillary thyroid cancer.

Prophylactic central neck dissection in papillary thyroid cancer is controversial. In this retrospective cohort study, the aim was to assess possible advantages of prophylactic central neck dissection with total thyroidectomy in cN0 papillary thyroid cancer. A total of 244 consecutive patients with papillary thyroid cancer, without clinical and ultrasound nodal metastases (cN0), were evaluated out of 1373 patients operated for a thyroid disease at the Istituto Europeo di Oncologia, Milan, Italy from 1994 to 2006. Of these 244 patients, 126 (Group A) underwent thyroidectomy with central neck dissection, while 118 (Group B) underwent thyroidectomy alone. Demographic, clinical and pathological features were analysed. Overall recurrence rate was 6.3% (8/126) in Group A and 7.7% (9/118) in Group B, with a mean follow-up of 47 (Group A) and 64 (Group B) months. In Group A patients, 47% were pN1a and all patients with recurrence had nodal involvement (p = 0.002). Survival rate did not differ in the two groups. Nine patients were lost to follow-up. Group A patients were older and their tumours were larger in size; according to the pT distribution, a higher extra-capsular invasion rate was observed. The two groups were equivalent as far as concerns histological high risk variants and multifocality. Nodal metastases correlated with stage: pT1-2 vs. pT3-T4a, p = 0.0036. A lower risk of nodal metastases was related to thyroiditis (p = 0.0034). In conclusion, central neck metastases were predictive of recurrence without influencing prognosis. From data obtained, possible greatest efficacy of central neck dissection in pT3-4 papillary thyroid cancer without thyroiditis is suggested.