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Up to 28% of all patients who undergo open surgery will develop a ventral hernia (VH) in the post-operative period. VH surgery is a debated topic in the literature, especially in oncological patients due to complex management. We searched in the surgical database of the Hepatobiliary Unit of the National Cancer Institute of Naples “G. Pascale Foundation” for all patients who underwent abdominal surgery for malignancy from January 2010 to December 2018. Our surgical approach and our choice of mesh for VH repair was planned case-by-case. We selected 57 patients that fulfilled our inclusion criteria, and we divided them into two groups: biological versus synthetic prosthesis. Anterior component separation was used in 31 patients (54.4%) vs. bridging procedure in 26 (45.6%). In 41 cases (71.9%), we used a biological mesh while a synthetic one was adopted in the remaining patients. Of our patients, 57% were male (33 male vs. 24 female) with a median age of 65 and a mean BMI of 30.8. We collected ventral hernia defects from 35 cm2 to 600 cm2 (mean 205.2 cm2); 30-day complications were present in 24 patients (42.1%), no 30-day mortality was reported, and 21 patients had a recurrence of pathology during study follow-up. This study confirms VH recurrence risk is not related with the type of mesh but is strongly related with BMI and type of surgery also in oncological patients.

Simple Summary The increasing use of high-quality imaging techniques together with improved access to healthcare has led to an increase in the detection of thyroid nodules. Fine-needle aspiration cytology (FNAC) is currently considered the most accurate examination for the assessment of thyroid nodular disease. However, in about 25% of cases, FNAC leads to the diagnosis of an indeterminate thyroid nodule, which represents a problem because malignancy, although relatively low (up to 30%), cannot be excluded with certainty. According to the 2015 American Thyroid Association guidelines, patients with thyroid nodular disease with an indeterminate cytology can undergo, based on established factors, a total thyroidectomy or a hemithyroidectomy. However, if an intermediate or high-risk differentiated thyroid carcinoma is detected after the hemithyroidectomy, through histological examination, the above-mentioned guidelines recommend performing a completion thyroidectomy. The main aim of this study was to assess the rate of complications in patients undergoing a completion thyroidectomy after a hemithyroidectomy for a thyroid nodule with an indeterminate cytology. There is still controversy as to whether patients undergoing a completion thyroidectomy after a hemithyroidectomy for a thyroid nodule with an indeterminate cytology have a comparable, increased or decreased risk of complications compared to those submitted to primary thyroid surgery. The main aim of this study was to investigate this topic. Patients undergoing a thyroidectomy for thyroid nodular disease with an indeterminate cytology in four high-volume thyroid surgery centres in Italy, between January 2017 and December 2020, were retrospectively analysed. Based on the surgical procedure performed, four groups were identified: the TT Group (total thyroidectomy), HT Group (hemithyroidectomy), CT Group (completion thyroidectomy) and HT + CT Group (hemithyroidectomy with subsequent completion thyroidectomy). A total of 751 patients were included. As for the initial surgery, 506 (67.38%) patients underwent a total thyroidectomy and 245 (32.62%) a hemithyroidectomy. Among all patients submitted to a hemithyroidectomy, 66 (26.94%) were subsequently submitted to a completion thyroidectomy. No statistically significant difference was found in terms of complications comparing both the TT Group with the HT + CT Group and the HT Group with the CT Group. The risk of complications in patients undergoing a completion thyroidectomy after a hemithyroidectomy for a thyroid nodule with an indeterminate cytology was comparable to that of patients submitted to primary thyroid surgery (both a total thyroidectomy and hemithyroidectomy).

Introduction. Parathyroid carcinoma is one of the rarest cancers in normal population, and it is extremely uncommon in the setting of tertiary hyperparathyroidism. Indeed, only 24 cases have been reported in the literature. Presentation of the Case. We report the case of parathyroid carcinoma in a 51-year-old man, with a history of end-stage renal disease due to a horseshoe kidney treated with haemodialysis since 2013. He came to our attention due to an increase in calcium and parathyroid hormone serum levels. Neck ultrasound (US) showed a solid hypodense mass, probably the right inferior parathyroid gland, with an estimated size of 25 × 15 × 13 mm; the 99mTc-sestamibi SPECT/CT scan revealed a large radiotracer activity area in the right cervical region, compatible with a hyperfunctioning right inferior parathyroid gland. So, a tertiary hyperparathyroidism diagnosis was made. In April 2018, resection of three parathyroid glands was performed. Histopathological examination demonstrated the right inferior parathyroid gland specimen to be a parathyroid carcinoma, due to the presence of multiple, full-thickness, capsular infiltration foci, and a venous vascular invasion focus. Discussion. Diagnosis of parathyroid carcinoma in tertiary hyperparathyroidism is remarkably complex because of the lack of clinical diagnostic criteria and, in many cases, is made postoperatively at histopathological examination. Conclusion. To date, radical surgery represents the mainstay of treatment, with a five- and ten-year survival rates overall acceptable.

Family history of thyroid cancer increases the risk of harboring thyroid malignancies that end up having extrathyroidal extension (ETE) and multifocality on histology, some authors suggest a more aggressive surgical approach. Their pre-operative identification could allow more conservative surgical procedures if none of these features are suspected. Our aim was to assess if neck ultrasonography could identify or exclude multifocality or ETE in these patients to tailor the extent of surgery. This retrospective study included patients with previous thyroid surgery, ≥1 first-grade relative with thyroid cancer, and who had undergone pre-surgical ultrasound. ETE was suspected in the case of thyroid border interruption or gross invasion of perithyroidal tissues. Multiple suspicious nodules were defined as suspicion of multifocal cancer. The cohort consisted of 45 patients (median age 49 years, 40 with thyroid cancer, 30 females). The positive predictive value of ultrasonography in predicting multifocality and ETE was 57.14% (25.25–84.03) and 41.67% (21.5–65.1%), respectively, while the negative predictive values were 63.2% (56.4–69.4%) and 72.7% (63.3–80.5%). Pre-operative ultrasound examination is unable to reliably identify or exclude multifocal disease or extrathyroidal extension. In patients scheduled for surgery and with a first-degree relative affected by DTC, a “negative” pre-operative US report does not exclude the potential finding of multifocality and ETE at final histopathology.

Lateral neck dissection (LND) leads to a significant morbidity involving accessory nerve injury. Modified radical neck dissection (MRND) aims at preservation of the accessory nerve, but patients often present with negative functional outcomes after surgery. The role of neuromonitoring (IONM) in the prevention of shoulder syndrome has not yet been defined in comparison to nerve visualization only. We retrospectively analyzed 56 thyroid cancer patients who underwent MRND over a period of six years (2015–2020) in a high-volume institution. Demographic variables, type of surgical procedure, removed lymph nodes and the metastatic node ratio, pathology, adoption of IONM and shoulder functional outcome were investigated. The mean number of lymph nodes removed was 15.61, with a metastatic node ratio of 0.2745. IONM was used in 41.07% of patients, with a prevalence of 68% in the period 2017–2020. IONM adoption showed an effect on post-operative shoulder function. There were no effects in 89.29% of cases, and temporary and permanent effects in 8.93% and 1.79%, respectively. Confidence intervals and two-sample tests for equality of proportions were used when applicable. Expertise in high-volume centres and IONM during MRND seem to be correlated with a reduced prevalence of accessory nerve lesions and limited functional impairments. These results need to be confirmed by larger prospective randomized controlled trials.

It has been more than five years since the American Thyroid Association (ATA) and the Italian consensus on thyroid cancer was published [...]

Thyroid cancer is the most common endocrine malignancy, representing 2.9% of all new cancers in the United States. It has an excellent prognosis, with a five-year relative survival rate of 98.3%.Differentiated Thyroid Carcinomas (DTCs) are the most diagnosed thyroid tumors and are characterized by a slow growth rate and indolent course. For years, the only approach to treatment was thyroidectomy. Active surveillance (AS) has recently emerged as an alternative approach; it involves regular observation aimed at recognizing the minority of patients who will clinically progress and would likely benefit from rescue surgery. To better clarify the indications for active surveillance for low-risk thyroid cancers, we reviewed the current management of low-risk DTCs with a systematic search performed according to a PRISMA flowchart in electronic databases (PubMed, Web of Science, Scopus, and EMBASE) for studies published before May 2021. Fourteen publications were included for final analysis, with a total number of 4830 patients under AS. A total of 451/4830 (9.4%) patients experienced an increase in maximum diameter by >3 mm; 609/4830 (12.6%) patients underwent delayed surgery after AS; metastatic spread to cervical lymph nodes was present in 88/4213 (2.1%) patients; 4/3589 (0.1%) patients had metastatic disease outside of cervical lymph nodes. Finally, no subject had a documented mortality due to thyroid cancer during AS. Currently, the American Thyroid Association guidelines do not support AS as the first-line treatment in patients with PMC; however, they consider AS to be an effective alternative, particularly in patients with high surgical risk or poor life expectancy due to comorbid conditions. Thus, AS could be an alternative to immediate surgery for patients with very-low-risk tumors showing no cytologic evidence of aggressive disease, for high-risk surgical candidates, for those with concurrent comorbidities requiring urgent intervention, and for patients with a relatively short life expectancy.

BACKGROUND Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. METHODS In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up. RESULTS In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. CONCLUSIONS The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

L’identificazione routinaria e la visualizzazione diretta del nervo laringeo ricorrente (NLR) sono riconosciute in tutto il mondo come i gold standard nella tecnica di dissezione della tiroide. Il neuromonitoraggio intraoperatorio (IONM) puo completare l’informazione offerta dall’identificazione diretta attraverso un’analisi funzionale. L’esperienza oramai decennale in Italia con il neuromonitoraggio ha notevolmente contribuito a una piu estesa comprensione della fisiopatologia della paralisi del NLR. Il vantaggio principale dello IONM, tuttavia, e la possibilita di riconoscere una paralisi del NLR visivamente non rilevabile, identificando i potenziali meccanismi di danno e, talvolta, riducendo il rischio di un danno nervoso bilaterale. Poiche la perdita del segnale intraoperatorio puo richiedere una modifica della strategia chirurgica preoperatoriamente pianificata, le presenti raccomandazioni forniscono informazioni sulle possibilita e sui limiti dello IONM nel momento decisionale di una perdita del segnale intraoperatoria. Ci si augura, comunque, che ulteriori studi, il progressivo affinamento della tecnologia e la corretta applicazione dello IONM nella chirurgia tiroidea si evolvano in modo significativo nei prossimi anni.

La tecnica del monitoraggio intraoperatorio continuo (CIONM) del nervo laringeo ricorrente (NLR) e riconosciuta come uno strumento utile per riconoscere le lesioni nervose imminenti e interrompere la relativa manovra chirurgica per prevenire le lesioni permanenti durante la tiroidectomia. Il CIONM fornisce costantemente preziose informazioni in tempo reale, il che e molto utile durante interventi chirurgici complessi della tiroide, specialmente in contesti di anatomia insolita. Il CIONM supera la limitazione metodologica inerente al neuromonitoraggio intermittente (IINOM). L’evento elettromiografico (EMG) combinato clinicamente importante (riduzione ampiezza e aumento latenza del segnale EMG), indicativo di imminente lesione del NLR, previene la maggior parte delle lesioni legate alla trazione del NLR anatomicamente intatto consentendo la modifica della manovra chirurgica che ne e causa nell’80% dei casi. Come ulteriore estensione, il CIONM aiuta anche a identificare il recupero del nervo funzionale intraoperatorio, qualora avvenga una ripresa del valore di ampiezza ≥50% rispetto ai valori della baseline iniziale; cio consente di continuare la resezione del lato controlaterale. Il CIONM facilita un’azione correttiva precoce prima che sia stato fatto un danno permanente al NLR. Il CIONM e una tecnica recente ma in rapida evoluzione, in via di perfezionamento da vari studi incentrati sul miglioramento della sua attuazione e interpretazione, nonche sull’eliminazione degli ostacoli tecnici.

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) represents the most performed bariatric surgical procedure worldwide. Morbid Overweight in elderly patients is becoming a significant health problem even in Italy. As well as in younger age groups, bariatric surgery could be indicated even in this subset of patients. However the advantages and results of LSG in patients over 60 years old have received minimal attention. METHODS The records of 375 patients underwent LSG between 2008 and 2016 were reviewed. In the entire series 18 patients were aged 60 years or older at the time of surgery. Since a 3 years follow-up was available for 12 patients out of the 18 aged over 60 we included in the study only these. General epidemiologic data, clinical findings, BMI and comorbidities surgical treatment and follow-up data were collected; postoperative measurements such as operative time, intraoperative complications, mortality rate, length of stay, incidence of early and late complications, Body mass Index (BMI), excess weight loss rate (EWL%) and comorbidities resolution were also recorded. RESULTS LSG was successfully performed for all geriatric patients. Global complications rate was 16.6% At 3 years mean BMI was 34.4±3.8 with a mean EWL% 66.1±31.9. Postoperative resolution of obesity comorbidities was observed; Hypertension (71.4%), type 2 Diabetes Mellitus (T2DM) (50.0%), obstructive sleep apnea syndrome (OSAS) (66.6%) respectively. No intraoperative complications or mortality were recorded. CONCLUSIONS LSG offered cure in geriatric patients affected by morbid obesity for weight loss and comorbidities resolution. Larger studies are necessary to analyze and minimize the incidence of postoperative complications associated to this surgical procedure in elderly patients.

The role of prophylactic central lymph node dissection (pCLND) in the treatment of differentiated thyroid cancer (DTC) is controversial and still a matter of debate. The primary outcome of our study was to assess whether pCLND is effective in reducing the incidence of recurrent disease, and the secondary goal was to estimate the incidence of postoperative complications in patients who underwent pCLND and to evaluate the prognostic value of occult node metastases. In this retrospective study, we included patients with preoperative diagnosis of DTC and clinically uninvolved lymph nodes (cN0). The patients were divided into two groups, depending on the surgical approach: total thyroidectomy alone (TT group) or total thyroidectomy and pCLND (pCLND group). Three hundred and ninety-nine patients were included in this study, 320 (80.2%) in the TT group and 79 (19.8%) in the pCLND group. There were no significant differences in morbidity among the two groups. Histopathological evaluation demonstrated a similar distribution of aggressive features, especially regarding multicentricity, extrathyroidal extension, and angioinvasivity between the two groups. Occult lymph node metastases were found in 20 (25.3%) patients in the pCLND group. Prophylactic CLND was effective in improving disease-free survival in patients with intermediate and high risk of disease recurrence (p = 0.0392), occult lymph node metastases resulted as a significant negative prognostic factor (p &lt, 0.001).

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6–10 cases in 38.9% of the centers, 11–20 cases in 16.7%, 21–30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

Background Corrosive esophageal strictures are common. The severity of the strictures depends on type, quantity, duration of contact and concentration of the caustic substance ingested. Endoscopic balloon dilation and endoscopic bougienage are a cornerstone in the management of the benign esophageal strictures and are the most widely used treatments, but are expensive and invasive procedures. Case Presentation We report the case of an 82-year-old patient with a corrosive esophageal stricture treated for over 40 years by means of home self-bougienage. The procedure has been carried out for the longest lapse of time described in literature, with an excellent control of symptoms. In the case reported, after being carried out for more than 40 years, self-dilation allowed good quality of life and symptoms management, ensuring an excellent nutritional status. Conclusions Following an adequate patient training, self-dilatation can be a safe and effective option of treatment, avoiding frequent expensive hospital admissions for endoscopic esophageal dilatation.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies: novel therapeutic approaches beyond conventional chemotherapy are still lacking and prognosis remains poor, even for resectable patients (pts). Furthermore, there is an almost complete absence of validated predictive factors. Consequently, robust biomarkers for the early diagnosis and the prognostic stratification are urgently needed in clinical practice, especially in the context of neoadjuvant and adjuvant settings. In the last years, evidence revealed the crucial role of miRNAs in cancer initiation and progression, as well as in the chemo-resistance mechanisms, suggesting their use as clinical biomarkers. Material and methods: In this pilot study, we performed a microarray analysis to characterize global miRNA expression profile from surgical tissue samples collected from 20 resected PDAC pts pooled into 4 groups according to different clinico-pathological features: nodal metastases (N+/N-) and tumor grading (G2/G3). Results: According to expression patterns, we identified, among 384 miRNAs, a significant different modulation for 11 miRNAs associated to G2 vs G3 and for 7 miRNAs in N+ vs N- disease, suggesting a possible specific signature reflecting histological grade and nodal metastasis occurrence, respectively. We focused on 2 up-regulated (miR-138-5p and miR-518-3p) and 3 down-regulated (miR-215-5p, miR-519a-3p and miR-576-5p) miRNAs in N+ pts, and on 3 up-regulated (miR-1-3p, miR-31-5p and miR-205-5p) in G3 pts, in order to verify their possible implication in the molecular changes behind tumor differentiation and spread, as well as their potential use for prognostic and therapeutic purpose. A bio-informatic analysis was also performed, using different in silico tools, to study both high affinity miRNA targets and cross-regulated pathways among the upand down-regulated miRNAs. The results identified several associated targets involved in multiple signaling pathways commonly dysregulated in cancer. Finally, BRCA1/2 and RB1 miRNAs-mediated-modulation is actually ongoing, considering the pivotal role of these genes in some PDAC pts. Conclusion: These preliminary data provide a strong rationale to further investigate miRNAs expression in larger cohorts of PDAC pts, possibly integrating validated tissue miRNAs data with circulating miRNAs, in order to identify strong (and easily accessible) potential biomarker(s) with prognostic and/or predictive significance. Citation Format: Luca Pompella, Michela Falco, Carlo Caputo, Anna Grimaldi, Giuseppe Tirino, Severo Campione, Francesca Sparano, Maria Lucia Iacovino, Chiara Carmen Miceli, Carlo Molino, Marco Montella, Renato Franco, Gennaro Galizia, Giovanni Conzo, Vincenzo Napolitano, Annamaria Auricchio, Francesca Cardella, Fortunato Ciardiello, Michele Caraglia, Angela Lombardi, Gabriella Misso, Ferdinando De Vita. A pilot study of miRNA expression profile in surgically resected pancreatic ductal adenocarcinoma: Initial report from a bi-institutional cohort [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-052.

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. (C) 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Background: Nab-paclitaxel plus gemcitabine represents one of the standard regimens for first line treatment of metastatic pancreatic cancer (mPC). Few data are available on nab-paclitaxel plus gemcitabine in geriatric population. Our study aims to show whether this schedule can be feasible in the elderly as first-line treatment for mPC. Methods: We retrospectively analyzed the data of 64 mPC patients (>= 65 years old) treated according to the MPACT schedule. Results: Median age was 69.5 years (range, 65-80 years); after a median of 5 cycles administered (range, 1-12), the most common adverse events (AEs) were grade 2 alopecia (46.9%), anemia (17.2%) and hypertransaminasemia (10.9%); all grades neutropenia occurred in 20.3% of pts. Global incidence of grade 3 and 4 toxicities were 26.5% and 0%, respectively, and no patients stopped treatment due to unacceptable toxicity. Stable disease (SI)) was observed in 31.2% of patients, with a disease control rate (DCR) and overall response rate of 57.8% and 26.6%, respectively. After a median follow-up of 18 months, median progression free survival (PFS) was 8 months (95% CI: 6.3-9.6) and median OS was 12.0 months (95% CI: 8.4-15.6). The univariate analysis for overall survival (OS) showed that only ECOG performance status was an independent prognostic factor for survival. Conclusions: Nab-paclitaxel plus gemcitabine schedule is feasible and effective in the "daily clinical practice" geriatric population.

Nab-paclitaxel plus gemcitabine (Nab-Gem) represents one of the standard regimen for first-line treatment of metastatic pancreatic adenocarcinoma (mPDAC). However, few data are available in mPDAC relapsed after gemcitabine as adjuvant treatment. Our study aims to evaluate the efficacy and feasibility of Nab-Gem as first-line treatment for mPDAC patients previously treated with adjuvant treatment. We retrospectively analyzed the safety and efficacy data of 36 patients, who received first-line Nab-Gem after gemcitabine as adjuvant treatment. All patients received gemcitabine after radical surgery. Median disease-free survival was 12 months (95% CI 9.7-14.3); at relapse, all patients received Nab-Gem. We observed an objective response rate and disease control rate of 11.1% and 63.9%, respectively. With a median follow-up of 47 months, median progression-free survival was 5 months (95% CI 1.0-9.0), whereas median overall survival (OS) was 13 months (95% CI 5.5-20.5). Median OS was higher in patients with a relapse >= 7 months after the end of adjuvant treatment than in patients relapsed < 7 months (14 vs. 8 months, respectively, p: 0.52). Our results show that first-line Nab-Gem is feasible and effective in patients previously treated with gemcitabine as adjuvant treatment.

Although therapeutic central neck dissection is recommended for patients with differentiated thyroid cancer with cervical lymph node metastasis, the effectiveness of prophylactic central neck dissection following total thyroidectomy in patients with clinical node-negative differentiated thyroid cancer remains controversial. There are many arguments in favor and many against the execution of prophylactic central neck dissection. The authors review the most recent literature and illustrate the latest published guidelines, focusing on the currently hottest and most debated points. Authors conclude that there is still no consensus on the role of prophylactic central neck dissection in clinically node-negative differentiated thyroid carcinoma. Prophylactic central neck dissection is associated with higher rates of hypoparathyroidism and recurrent laryngeal nerve injury with uncertain benefits. So, in the absence of involved lymph nodes, prophylactic central neck dissection should be avoided, reserving it to high-risk patients with advanced primary tumors; prophylactic central neck dissection should be performed by high-volume surgeons to avoid definitive complications.

Background Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. Methods Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. Results Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8–38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. Conclusions Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Background The gold standard approach for surgical treatment of benign and malignant adrenal lesion is considered the laparoscopic one, due to a lot of advantages compared to open approach. The rapid propagation of this surgical technique is due to the diffusion of haemostatic devices in laparoscopic adrenal surgery. The principal aim of this study is to analyze the outcome of LA using each energy modality, evaluating the eventual superiority of an instrument over the others. Methods A retrospective study, involving 75 consecutive patients submitted to LA by transperitoneal lateral approach from January 2013 to June 2017, was performed. Age less than 70 years old, adrenal adenomas less than 8 cm in diameter, incidentalomas 0.05). Significant statistical difference are detectable in operation time and intraoperative blood losses. Thunderbeat, compared respectively with Ligasure and Harmonic Scalpel, is the fastest device (p

Background The association between Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a controversial question that is still under debate, its pathological significance and the eventual clinical implications of this association remaining unclear. Methods The data regarding 305 patients were retrospectively analyzed. The patients were divided in two different groups. A first group made up of 142 patients undergoing surgery for differentiated thyroid carcinoma was compared to a control group of 142 analogous subjects operated for normofunctioning goiter. A second group was made up of 163 patients who had undergone total thyroidectomy (TT) with pre-operative diagnosis of HT. Results In the first group of patients an association with HT was found in 28,6% of the patients with final histopathological diagnosis of PTC versus 7,7% of the patients with histopathological diagnosis of multinodular goiter, which was a significant difference (p

Pancreatic neuroendocrine tumors (pNETs) represent about 7% of all NETs, 8.7% of gastroenteropancreatic NETs (GEP-NETs) and 1-2% of all pancreatic neoplasms. In the last two decades, the increased diagnosis of pNETs has generated great interest and the development of different classifications, grading and staging systems. Recently, several trials were performed in order to improve the knowledge of biomarkers and imaging and to provide an early diagnosis, but their role is still under debate. Nowadays, surgery represents the only curative approach for pNETs. Approximately 90% of pNETs are silent and non-functional; therefore, most patients are diagnosed in late stage and present metastatic (60%) or locally unresectable advanced disease (21%) with a poor prognosis. Not many therapeutic options are available for pNETs, with different treatments for G1-G2 and G3 tumors, because these diseases are still rare and trials are made up of few series of patients. At present, medical treatments is controversial. On these bases, we believe that a multidisciplinary team composed of surgeons, oncologists, endocrinologists, radiation oncologists, radiologists, pathologists and medicals nuclear is required. This paper presents a review of present state-of-the-art in the field of pNETs. Pancreatic neuroendocrine tumors (pNETs) represent about 7% of all NETs, 8.7% of gastroenteropancreatic NETs (GEP-NETs) and 1-2% of all pancreatic neoplasms. In the last two decades, the increased diagnosis of pNETs has generated great interest and the development of different classifications, grading and staging systems. Recently, several trials were performed in order to improve the knowledge of biomarkers and imaging and to provide an early diagnosis, but their role is still under debate. Nowadays, surgery represents the only curative approach for pNETs. Approximately 90% of pNETs are silent and nonfunctional; therefore, most patients are diagnosed in late stage and present metastatic (60%) or locally unresectable advanced disease (21%) with a poor prognosis. Not many therapeutic options are available for pNETs, with different treatments for G1-G2 and G3 tumors, because these diseases are still rare and trials are made up of few series of patients. At present, medical treatments is controversial. On these bases, we believe that a multidisciplinary team composed of surgeons, oncologists, endocrinologists, radiation oncologists, radiologists, pathologists and medicals nuclear is required. This paper presents a review of present state-of-the-art in the field of pNETs. (c) 2016 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.

Background Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (

Background Pancreatic neuroendocrine tumors (pNETs) are uncommon entities. pNETs are often small, slow growing, clinically silent neoplasms. However, they have an almost unpredictable biological behaviour with a not negligible malignant potential. Surgery still represents the treatment of choice, but the high morbidity associated to the enucleation or the formal pancreatectomy should be considered in the decision of the proper treatment. Management of these neoplasms is still debated, and indications for a conservative observational approach and for parenchyma sparing resections are not yet standardized. Method We review the state of art on the indications for the conservative management of pNETs. Searches on MEDLINE database were performed to identify articles reporting prognostic systems, biochemical screening, observational management, medical treatment and surgical strategies for pNETs. Discussion Currently, an accurate ‘wait-and-see' policy is recommended by the European Neuroendocrine Tumor Society (ENETS) only for non-functioning pNETs (NF-pNETs) A biochemical screening, based on sampling of serum levels of pancreatic polypeptide (PP) and chromogranin A, can address to early conservative surgery for MEN-1 associated NF-pNETs The subtotal (80%) distal pancreatectomy first proposed by Thompson, often with the enucleation of possible pancreatic head tumors, still represents a good compromise between oncological radicality and prevention of pancreatic endocrine/exocrine insufficiency caused by standard radical resections for the treatment of inherited syndromes associated with NF-pNETs >2 cm and symptomatic F-pNETs of any size. Conclusion More studies are needed to further clarify and predict the biologic behaviour of pNETs and increase the indications for conservative observational management and parenchyma sparing pancreas resections.

Objective: In our Pathology Department, fine needle aspiration (FNA) of palpable thyroid nodules isperformed by cytopathologists who ensure correct sample management and rapid on-site evaluation (ROSE).Conversely, ultrasound (US)-guided FNAs have traditionally been carried out by endocrinologists andradiologists in outside clinics, where the presence of a cytopathologist is not always feasible. To overcome thislimitation, cytopathologists have started to perform US-guided FNAs themselves. This study retrospectivelyevaluates 1 year of this novel practice.Methods: A total of 2225 US-guided FNAs were performed in our clinic by cytopathologists, whereas 1490aspirates were taken by a group of non-cytopathologists. Among these, 756 FNAs were taken by a singleexperienced endocrinologist. The distribution of the Bethesda classification categories was evaluated in each ofthese groups.Results: FNAs performed by cytopathologists were more often diagnostic and better prepared than thosetaken by non-cytopathologists, including those taken by the experienced endocrinologist (P < 0.01). The latteroperator yielded a higher rate of suspicious and malignant FNAs, reflecting a more appropriate clinical triageof worrisome nodules.Conclusion: Although the endocrinologist’s evaluation is crucial to select clinically relevant thyroid nodules,cytopathologists can reliably perform US guidance in addition to their traditional expertise in sampling,specimen preparation and ROSE.Keywords: ultrasound-guided fine needle aspiration, thyroid, rapid on-site evaluation, interventionalpathologistIntroductionThyroid fine needle aspiration (FNA) is a reliableand cost-effective diagnostic tool, as long as high-quality samples, representative of the lesion, areobtained for accurate microscopic interpretation. Theideal physician to perform thyroid FNA should beone who is skilled in obtaining representative mate-rial and in the preparation of slides. As these skillsare strengthened by the microscopic observation ofsamples, it is not surprising that the best results onpalpable nodules are obtained when the FNA is per-formed or triaged by the same cytopathologist whowill eventually make the diagnosis.

Several studies in the last years demonstrated the better surgical outcome of laparoscopic approach to adrenal gland. Laparoscopic surgery is more difficult to learn and requires different psychomotor skills than open surgery, especially with regard to complex maneuvers requiring precision and dexterity. The development of robotic platform with three-dimensional vision and increased degrees of freedom of the surgical instruments has the aim to overcome these problems. We performed a systematic literature review with meta-analysis to evaluate preoperative data and surgical outcomes of robotic adrenalectomy compared with laparoscopic technique. In September 2016 we performed a systematic literature review using the Pubmed, Scopus and ISI web of knowledge database with search term "robotic adrenalectomy". We identified 13 studies with eligible criteria that compared surgical outcomes. This present systematic review with meta-analysis includes 798 patients: 379 underwent to robotic adrenalectomy (cases group) and 419 to laparoscopic adrenalectomy (controls group). There were no significant differences between the two groups of patients respect to age, gender, laterality and tumor size. BMI instead was significant lower in the robotic group. In this group we found also patients with higher incidence of previous abdominal surgery. The results from operative time demonstrated lower operative time for laparoscopic group but there were no significant differences with robotic group. Robotic adrenalectomy showed a significant lower blood loss. Robotic adrenalectomy is a safe and feasible technique with reduced blood loss and shorter hospital stay than laparoscopic adrenalectomy. Laparoscopic approach seems to be a more rapid technique when comparing to robotic technique, although recent studies demonstrate a significant operative time reduction in robotic group with the learning curve improvement and the development of new surgical technology.

The triad composed by α-Klotho, fibroblast growth factor-23, and its receptor are involved in the pathogenesis of chronic kidney disease–mineral and bone disorder. A disintegrin and metalloproteinase 17 (ADAM17) is a metalloproteinase causing the proteolytic shedding of α-Klotho from the cell membrane, and its role in chronic kidney disease–mineral and bone disorder is not yet known. We studied the circulating levels of the above-mentioned mediators in patients with secondary hyperparathyroidism due to uremia, compared to control subjects, as well as in patients with primary hyperparathyroidism. We also measured the immunofluorescence pattern of the relevant tissue proteins in specimens obtained from patients undergoing parathyroid surgery for secondary compared to primary hyperparathyroidism. Results showed that α-Klotho tissue levels are reduced, in the presence of increased ADAM17 tissue levels. In addition, we showed increased serum levels of the main product of ADAM17 proteolytic activity, tumor necrosis factor-α. Thus, we found a paradoxical situation, in secondary compared to primary hyperparathyroidism, that is, that in the face of increased tumor necrosis factor-α in circulation, both soluble and tissue α-Klotho are reduced significantly, despite increased tissue ADAM17. In conclusion, tissue and serum levels of α-Klotho seem to have become independent from the regulation induced by ADAM17, which constitutes therefore another tassel in the impaired α-Klotho–FGF23 receptor axis present in uremia.

The most appropriate surgical management of "follicular neoplasm/suspicious for follicular neoplasm" lesions (FN), considering their low definitive malignancy rate and the limited predictive power of preoperative clinic-diagnostic factors, is still controversial. On behalf of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB), we collected and analyzed the experience of 26 endocrine centers by computerized questionnaire. 1379 patients, surgically treated after a FN diagnosis from January 2012 and December 2103, were evaluated. Histological features, surgical complications, and medium-term outcomes were reported. Total thyroidectomy (TT) was performed in 1055/1379 patients (76.5 %), while hemithyroidectomy (HT) was carried out in 324/1379 cases (23.5 %). Malignancy rate was higher in TT than in HT groups (36.4 vs. 26.2 %), whereas the rates of transient and definitive hypoparathyroidism following TT were higher than after HT. Consensual thyroiditis (16.8 vs. 9.9 %) and patient age (50.9 vs. 47.9 %) also differed between groups. A cytological FN diagnosis was associated to a not negligible malignancy rate (469/1379 patients; 34 %), that was higher in TT than in HT groups. However, a lower morbidity rate was observed in HT, which should be considered the standard of care in solitary lesions in absence of specific risk factors. Malignancy could not be preoperatively assessed and clinical decision-making is still controversial. Further efforts should be spent to more accurately preoperatively classify FN thyroid nodules. The most appropriate surgical management of “follicular neoplasm/suspicious for follicular neoplasm” lesions (FN), considering their low definitive malignancy rate and the limited predictive power of preoperative clinic-diagnostic factors, is still controversial. On behalf of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB), we collected and analyzed the experience of 26 endocrine centers by computerized questionnaire. 1379 patients, surgically treated after a FN diagnosis from January 2012 and December 2103, were evaluated. Histological features, surgical complications, and medium-term outcomes were reported. Total thyroidectomy (TT) was performed in 1055/1379 patients (76.5 %), while hemithyroidectomy (HT) was carried out in 324/1379 cases (23.5 %). Malignancy rate was higher in TT than in HT groups (36.4 vs. 26.2 %), whereas the rates of transient and definitive hypoparathyroidism following TT were higher than after HT. Consensual thyroiditis (16.8 vs. 9.9 %) and patient age (50.9 vs. 47.9 %) also differed between groups. A cytological FN diagnosis was associated to a not negligible malignancy rate (469/1379 patients; 34 %), that was higher in TT than in HT groups. However, a lower morbidity rate was observed in HT, which should be considered the standard of care in solitary lesions in absence of specific risk factors. Malignancy could not be preoperatively assessed and clinical decision-making is still controversial. Further efforts should be spent to more accurately preoperatively classify FN thyroid nodules.

Prophylactic central neck dissection in clinically node-negative patients remains controversial. The aim of this multicenter retrospective study was to determine the rate of metastases in the central neck in clinically node-negative differentiated thyroid cancer patients, to examine the morbidity, and to assess the risk of regional recurrence in patients treated with total thyroidectomy with concomitant bilateral or ipsilateral central neck dissection compared with those undergoing total thyroidectomy alone. 258 consecutive clinically node-negative patients were divided into three groups according to the procedures performed: total thyroidectomy only (group A), total thyroidectomy with concomitant ipsilateral central neck dissection (group B), and total thyroidectomy combined with bilateral central neck dissection (group C). Mean operative time and postoperative stay were shorter in Group A (p < 0.01). The incidence of postoperative transient hypoparathyroidism was lower in Group A (p = 0.03), whereas no differences in the incidence of permanent hypoparathyroidism and nerve palsy were present. Postoperative radioactive iodine administration was higher in group B and particularly C (p = 0.03) compared with group A. There were no statistically significant differences in terms of regional recurrence. Differentiated thyroid cancer has a high rate of central lymph node metastasis even in clinically node-negative patients; in the present study there was no statistically significant difference in the rates of locoregional recurrence between the three modalities of treatment. Total thyroidectomy appears to be an adequate treatment for clinically node-negative differentiated thyroid cancer. Prophylactic central neck dissection might be considered for differentiated thyroid cancer patients with large tumor size or extrathyroidal extension.

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 asMEN2A, 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. (C) 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Introduction Aim of this study is to determine whether quality of life (QoL) assessment in association with instrumental evaluation can help to identify factors predictive of outcome both in surgically and medically treated GERD patients. Methods Between January 2005 and June 2010, 301 patients affected with GERD were included in the study. QoL was evaluated by means of GERD-HRQL and SF-36 questionnaires administered before treatment, at 6 months, at 1 year follow-up and at the end of the study. The multivariate analysis was used to detect if variables such as sex, age, heartburn, acid regurgitation, dysphagia, presence of esophagitis, percentage of total time at pH < 4, symptom index score (SI), the SF-36 and HRQL scores before treatment, at 6 months and 1 year could affect the QoL questionnaires scores at the end of the study. Results One hundred forty-seven patients were included in the surgical group and 154 in the medical group. No differences with regard to gender, age, mean SF-36 and HRQL scores before treatment were documented. At the end of the study, quality of life was significantly improved for SF-36 and HRQL scores, either for surgical or medical group. The multivariate analysis showed no factors individually affected the SF-36 and the HRQL scores, but symptom index score (SI) and QoL questionnaires scores at 6 months and 1 year follow-up. Conclusions The combined use of pHmetry with evaluation of SI and QoL questionnaires can predict the outcome of GERD patients managed either by medical or surgical therapy.

A frequent complication of thyroid surgery is laryngeal nerve palsy with transitory or permanent deficiency of cordal motility. Peripheral mono-or bilateral palsy in these cases may either occur, in adduction or abduction, and be complete or not complete. Bilateral vocal cords paralysis cause a persistent dyspnoic symptomatology with worsening during physical exercise or flogistic episodes of the upper airway: true vocal cords adduction, in median or paramedian position reduce the glottic space and increases respiratory resistances. Several surgical procedures have been proposed for the treatment of respiratory distress secondary to bilateral cord palsy. The aim of this study is to value the role of CO2 laser aritenoidectomy in 93 patients affected by bilateral paralysis in adduction of true vocal cords. Pre and postoperative evaluations included clinical results, spirometry, aerodynamics studies and evaluation of foniatric performance (MPT, H/N Ratio, Jitter and Shimmer) with a mean follow-up of 12 years. CO2 laser aritenoidectomy induces a complete resolution of respiratory failure, maintaining a good vocal quality, minimum surgical stress with low percentage of complications and a short hospitalization.

The most appropriate surgical management of "follicular neoplasm/suspicious for follicular neoplasm" lesions, is still controversial. Analysing and comparing the experience of two units for endocrine surgery, we retrospectively evaluated 721 patients, surgically treated after a follicular neoplasm diagnosis. Total thyroidectomy was routinely performed in one Institution, while in the other one it was selectively carried out. The main criteria leading to hemythyroidectomy were a single nodule, the age ≤45 years, the absence of thyroiditis or clinical/intraoperative suspicion of malignancy. Total thyroidectomy was performed in 402/721 patients (55.7%), hemythyroidectomy in 319/721 cases (44.2%) and a completion thyroidectomy in 51/319 cases (15.9%). The overall malignancy rate was 24% (176/721 patients), respectively 16% (51/319 patients) following hemythyroidectomy, and 31% (125/402 patients) following total thyroidectomy. Definitive recurrent laryngeal nerve paralysis and permanent hypoparathyroidism were not reported in hemythyroidectomy patients in which lower mean hospitalization and costs were observed. Considering the low-risk of follicular neoplasm solitary lesions, hemythyroidectomy is still the safest standard of care with lower hospitalization and costs. In case of multiglandular disease or thyroiditis, that might be associated with a higher risk of cancer, total thyroidectomy should be recommended. Further investigation is warranted to achieve a better preoperative follicular neoplasm diagnostic accuracy in order to reduce the amount of unnecessary surgical operations with a diagnostic aim.

Objective: The ultrasonic scalpel is a surgical shear that uses high-frequency mechanical energy to enable simultaneous vessel sealing and tissue coagulation at the same time. We conducted a prospective study to compare the outcome of total thyroidectomy using the ultrasonic scalpel versus the device Ligasure in terms of safety, operative time, overall drainage volume, complications, hospital stay. Methods: Between January 2008 and December 2013,400 patients (260 women, 140 men; mean age 46 years) undergoing thyroidectomy were randomized into two groups: group A, where Ultracision were used, and group B, where the Ligasure device was used. Results: There was no significant differences between the two groups in terms of age, gender, indication for thyroidectomy, thyroid gland weight and diameter, histopathologic diagnosis, preoperative and postoperative serum calcium levels, postoperative complications and reoperative thyroid surgery, time of operation and amount of drainage. Conclusions: The ultrasonic scalpel and the Ligasure ares safe, effective, useful, and time-saving alternative to the traditional suture ligation technique for thyroid surgery. They simplified total thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving efficient hemostasis.

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.

Introduction: Fluoropyrimidines such as 5-fluorouracil (5-FU) and its orally active prodrug, capecitabine, are widely used in the treatment of gastrointestinal cancer, including colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) plays an important role in the 5-FU metabolism. Dihydropyrimidine dehydrogenase gene (DPYD) is a highly polymorphic gene with several hundreds of reported genetic variants and DPD activity levels vary considerably among individuals, with different 5-FU-related efficacy and toxicity. About 5% of the population is deficient in DPD enzyme activity. The most well studied DPYD variant is the IVS14+1G>A, also known as DPYD ∗2A. In this report, we present a case of a patient with a double heterozygote DPYD variant (DPYD activity score: 0,5 according to Clinical Pharmacogenetics Implementation Consortium) who experienced a severe fluoropyrimidine-related toxicity resolved without any consequence. Patient concerns: A 46-years-old Caucasian man with diagnosis of left colon adenocarcinoma underwent left hemicolectomy on July 2017: pT3 G3 N1c M0. According to the disease stage, he started an adjuvant therapy with XELOX using capecitabine at 50% of total dose, because of his DPYD IVS14+1G>A variant, detected before the treatment. DIAGNOSIS: After few days, despite of this dose reduction, he experienced life-threatening adverse events such as mucositis G3, diarrhea G3, neutropenia G4, thrombocytopenia G4, and hyperbilirubinemia G3 according to Common Terminology Criteria for Adverse Events v 5.0. Interventions: As first, we set up an intensive rehydration therapy, antibiotic and antifungal prophylaxis, Granulocyte-Colony Stimulating Factors, and supportive blood transfusions. Additional genetic tests revealed a double heterozygote variant of DPYD gene (DPYD IVS14+1G>A and 2846A>T) which is a very rare situation and only 3 cases are described in literature, all of them concluded with patient's death. Outcomes: After 3 weeks of intensive therapy, the patient was fully recovered. Furthermore, all the whole-body CT scans performed since discharge from the hospital until now, have confirmed no evidence of disease. Conclusions: Recent studies demonstrated that screening strategy for the most common DPYD variants allowed for avoiding toxicities and saving money. This report underlines the importance of genotyping DPYD before treatment and emphasizes the role of genotype-guided dose individualization.