Impact of the COVID-19 Pandemic on Enhanced Recovery After Surgery (ERAS) Application and Outcomes: Analysis in the "Lazio Network" Database.

BACKGROUND: The aim of this study was to investigate how the COVID-19 pandemic influenced ERAS program application in colorectal surgery across hospitals in the Lazio region (central district in Italy) participating in the "Lazio Network" project. METHODS: A multi-institutional database was constructed. All patients included in this study underwent elective colorectal surgery for both malignant and benign disease between January 2019 and December 2020. Emergency procedures were excluded. The population was divided into 2 groups: a pre-COVID-19 group (PG) of patients operated on between February and December 2019 and a COVID-19 group (CG) of patients operated on between February and December 2020, during the first 2 waves of the pandemic in Italy. RESULTS: The groups included 622 patients in the PG and 615 in the CG treated in 8 hospitals of the network. The mean number of items applied was higher in the PG (65.6% vs. 56.6%, p < 0.001) in terms of preoperative items (64.2% vs. 50.7%, p < 0.001), intraoperative items (65.0% vs. 53.3%, p < 0.001), and postoperative items (68.8% vs. 63.2%, p < 0.001). Postoperative recovery was faster in the PG, with a shorter time to first flatus, first stool, autonomous mobilization and discharge (6.82 days vs. 7.43 days, p = 0.021). Postoperative complications, mortality and reoperations were similar among the groups. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the application of ERAS in the centers of the "Lazio Network" study group, with a reduction in adherence to the ERAS protocol in terms of preoperative, intraoperative and postoperative items. In addition, in the CG, the patients had worse postoperative outcomes with respect to recovery and discharge.

Enhanced recovery after surgery (ERAS) program in octogenarian patients: a propensity score matching analysis on the "Lazio Network" database.

PURPOSE: The aim of this study was to evaluate the safety and compliance with the enhanced recovery after surgery (ERAS) protocol in octogenarian patients undergoing colorectal surgery in 12 Italian high-volume centers. METHODS: A retrospective analysis was conducted in a consecutive series of patients who underwent elective colorectal surgery between 2016 and 2018. Patients were grouped by age (≥ 80 years vs < 80 years), propensity score matching (PSM) analysis was performed, and the groups were compared regarding clinical outcomes and the mean number of ERAS items applied. RESULTS: Out of 1646 patients identified, 310 were octogenarians. PSM identified 2 cohorts of 125 patients for the comparison of postoperative outcomes and ERAS compliance. The 2 groups were homogeneous regarding the clinical variables and mean number of ERAS items applied (11.3 vs 11.9, p-ns); however, the application of intraoperative items was greater in nonelderly patients (p 0.004). The functional recovery was similar between the two groups, as were the rates of postoperative severe complications and 30-day mortality rate. Elderly patients had more overall complications. Furthermore, the mean hospital stay was higher in the elderly group (p 0.027). Multivariable analyses documented that postoperative stay was inversely correlated with the number of ERAS items applied (p < 0.0001), whereas age ≥ 80 years significantly correlated with the overall complication rate (p 0.0419). CONCLUSION: The ERAS protocol is safe in octogenarian patients, with similar levels of compliance and surgical outcomes. However, octogenarian patients have a higher rate of overall complications and a longer hospital stay than do younger patients.

Salvage neck dissection for isolated neck recurrences in head and neck tumors: Intra and postoperative complications.

BACKGROUND AND OBJECTIVES: The current evidence regarding complications after salvage neck dissection (ND) for isolated regional recurrences (IRRs) in head and neck cancers is poor. The aim of this study is to evaluate the incidence and differences in complication rates of salvage ND after primary surgery, radiotherapy, chemoradiotherapy, or combined treatments. METHODS: This was a multicentric retrospective study on 64 patients who underwent salvage ND for IRR in three Italian institutes between 2008 and May 2020. RESULTS: Complications were detected in 7 of the 34 patients (20.8%) and surgeons described difficult dissection in 20 patients (58.82%). Accidental vascular ligations or nervous injury during surgery were never detected. None of the variables analyzed were statistically significant in predicting the risk of complications, disease-free survival, or overall survival. CONCLUSIONS: IRR represents a rare entity among total relapses. The incidence of complications after salvage ND for IRR is higher than after primary surgery but at an acceptable rate in experienced hands. However, an adequate balance between functional and oncological outcomes is mandatory.

Impact of implementation of the ERAS program in colorectal surgery: a multi-center study based on the "Lazio Network" collective database.

BACKGROUND: ERAS implementation improved outcomes in patients undergoing colorectal surgery. The process of incorporating this pathway in clinical practice may be challenging. This observational study investigated the impact of systematic ERAS implementation on surgical outcomes in patients undergoing colorectal resections in a regional network of 10 institutions. METHODS: Implementation of ERAS pathway was designed using regular audits and a common protocol. All patients undergoing elective colorectal surgery between 2016 and 2017 were considered eligible. A collective database including 18 ERAS items, clinical and surgical data, and outcomes was designed. Univariate and multivariate analyses were performed for the following outcomes: morbidity, anastomotic leak, reinterventions, hospital stay, and readmissions. RESULTS: A total of 827 patients were included, and a mean of 11.3 ERAS items applied/patient was reported. Logistic regression indicated that an increased number of ERAS items applied reduced overall and severe morbidity (OR 0.86 and 0.87, respectively 95%CI 0.8197-0.9202 and 95%CI 0.7821-0.9603), hospitalization (OR 0.53 95%CI 0.4917-0.5845) and reinterventions (OR 0.84 95%CI 0.7536-0.9518) in the entire series. The same results were obtained for a prolonged hospitalization differentiating right-sided (OR 0.48 95%CI 0.4036-0.5801), left-sided (OR 0.48 95%CI 0.3984-0.5815), and rectal resections (OR 0.46 95%CI 0.3753-0.5851). An inverse correlation was found between the application of ERAS items and morbidity in right-sided and rectal procedures (OR 0.89 and 0.84, respectively 95%CI 0.7976-0.9773 and 95%CI 0.7418-0.9634). CONCLUSIONS: Systematic implementation of the ERAS pathway using multi-institutional audits can increase protocol adherence and improve surgical outcomes in patients undergoing colorectal surgery.

Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management.

PURPOSE: Investigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients. MATERIALS AND METHODS: Behavioral and 24-hour pH- and impedance-monitoring data were prospectively analyzed for 25 laryngectomised patients with no previous history of GER in outpateints' setting. Reflux detected was characterized as either acid, weakly acidic or nonacid. Proximal reflux was found at 15cm above the LES. RESULTS: 40% of patients presented a pathological number of reflux episodes in the upright position (p<0.0001); 9 of them presented a pathologic bolus exposure time. Bolus exposure at the proximal sphincter was one fourth-fold lower than 5cm above the LES (p=0.3593). There was a prevalence of acid reflux at both sphincters (p<0.0001); liquid reflux was prevalent at the LES (p=0.003) and mixed reflux at the UES (p=0.0001). Median REs was higher than time acid exposure (p=0.0013). CONCLUSIONS: Pre- and post-surgical reflux investigation could identify preexisting reflux severity and screen potential high-risk cancer patients for postoperative complications. This might allow the early onset of acid suppressive therapy in presence of pathologic findings in high-complication risk cancer patients.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PURPOSE: Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. MATERIALS AND METHODS: We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). RESULTS: Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. CONCLUSIONS: Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis.

Right hepatic artery crossing the common hepatic artery: an unusual blood supply to the liver.

To perform hepatic surgery a precise preoperative and intraoperative study of liver vascular supply is mandatory. Detecting vascular variations may have great importance on surgical strategy and outcome, and details of anatomy do not concern only academical knowledge but become deeply involved in practice. We present a case of unusual blood supply to the liver, the common hepatic artery was directed to the right liver and a right hepatic artery originating from the superior mesenteric artery was directed to the left liver. The right hepatic artery crossed the common hepatic artery in the proximal part of the hepatic pedicle, anterior to the portal vein. To our knowledge this type of anatomical variation has not been described before and it represents a rare finding that has to be kept in mind, especially in case of major hepatectomies and more demanding splitting liver procedures such as A.L.P.P.S., in situ split, ex situ split and living donor liver transplantation.

Is open tracheotomy performed by residents in otorhinolaryngology a safe procedure? A retrospective cohort study.

Surgical or percutaneous tracheotomy is one of the commonest operations in the ENT practice and one of the first procedures to be taught to residents. No study exists that demonstrates the safety of this surgical procedure performed by unexperienced surgeons. The purpose was to compare outcomes of tracheotomies performed by supervised residents and surgeons in terms of postoperative complications and mortality, and identify risk factors for the onset of complications. Retrospective cohort study. Otolaryngology-Head and Neck Surgery Department, University of Florence, Italy. We included all patients undergoing tracheotomy from July 2008 to January 2013 and compared tracheotomies performed by supervised residents or surgeons. During the study period, 304 patients were submitted to tracheotomy. Patients operated by surgeons had a significantly higher number of tracheal rings fracture (p = 0.05), subcutaneous emphysema (p = 0.003) and tracheostomy tube displacement (p = 0.003), while supervised residents had a higher number of tracheitis/pneumonia (p = 0.04) as early complications. Patients operated by supervised residents had a significantly higher number of tube obstructions as late complication (p = 0.04). Using multivariate model, risk factors for early postoperative complications were male sex (p = 0.04) and delayed time to substitution with cuffless tube (p = 0.01), while only a trend to statistical significance was observed for urgent tracheotomies concerning the risk for late postoperative complications (p = 0.08). The current practice where residents perform tracheotomies supervised by a surgeon should not be disheartened. Our study demonstrates that it is safe and does not lead to higher risk of complications nor negatively affects the quality of care.

Detection of high levels of Survivin-immunoglobulin M immune complex in sera from hepatitis C virus infected patients with cirrhosis.

AIM: The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin-immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases. METHODS: Serum levels of Survivin-IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC). RESULTS: Survivin-IgM IC was lower in healthy subjects (median, 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P < 0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin-IgM IC (median, 633.71 AU/mL; P < 0.001). The receiver-operator curve analysis revealed that Survivin-IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin-IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin-IgM IC significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022). CONCLUSION: Our results suggest that Survivin-IgM immune complex may be used as a potential biomarker for liver damage, particularly for the identification of the HCV-related cirrhotic population.

The ALPPS procedure: a surgical option for hepatocellular carcinoma with major vascular invasion.

BACKGROUND: Hepatocellular carcinoma (HCC) tends to have a particular invasiveness toward the portal vein (PV) branches and hepatic veins. This situation can hamper major surgical resection with a risk of postoperative liver failure due to the small future liver remnant (FLR) in cirrhotic livers. These patients are then usually directed to palliative treatments with poor results. The associating liver partition and PV ligation (PVL) in staged hepatectomy (ALPPS) strategy is one of the main surgical innovations in recent years in the field of liver surgical oncology. The ALPPS approach could allow surgical resection in patients with HCC and associated major vascular invasion. METHODS: Among 1,143 liver resection performed in our center, the ALPPS approach was employed in order to induce rapid hypertrophy of the left FLR in patients with HCC and associated major vascular invasion. This strategy consists of combining the in situ splitting of the liver along the main portal scissura or on the right side of the falciform ligament and PVL in a strategy of staged hepatectomy. RESULTS: In our experience the ALPPS approach allowed us to achieve a sufficient FLR in two cases of HCC with major vascular invasion, in which the classic two-stage strategy could not be applied. In both cases the patients could undergo major hepatectomies without mortality. CONCLUSIONS: This novel strategy could expand the number of patients undergoing major liver resections that were previously considered non-resectable because of the risk of liver decompensation for an insufficient FLR.

Surgical options in radiotherapy-failed early glottic cancer.

After failure of curative radiotherapy (RT), surgery is the main therapeutic option to control recurrent laryngeal cancer. Recurrences after RT for T1-T2 tumours of the glottic larynx are often diagnosed at a more severe stage than the original disease and, thus, usually treated by radical approaches. Our aim is to investigate the feasibility of more conservative strategies for proper treatment of post-RT recurred glottic cancer. We collected and reviewed our files from 1990 to 2006, selecting 75 patients which matched the following inclusion criteria: (1) patient was originally diagnosed with early stage squamous cell carcinoma of the glottic larynx (stage I-II according to 2010 TNM), (2) patient was treated by RT with curative intent, (3) patient presented a recurrence of disease after RT which was surgically treated at our Institution. T stage at first diagnosis was T1a in 41 cases (55%), T1b in 12 (16%) and T2 in 22 (29%). At clinical examination of RT-recurred lesions, we documented advanced lesions (rT3-rT4) in 29 out of 75 patients (39%). Overall, an upstage was reported for 56% RT-recurred cancers, while 37.3% remained at the same stage than the original tumour and 6.7% were downstaged. Twelve patients (16%) underwent salvage partial laryngectomy (SPL), while 63 (84%) received a salvage total laryngectomy (STL). Multivariate analysis showed that rTNM according to the AJCC-UICC of 2010 was the only prognostic factor for both disease-free survival (p = 0.042) and overall survival (p = 0.004). Considering the prognostic impact of rT and rN we documented a statistical significance only in terms of overall survival for both factors (p = 0.004 and p = 0.04, respectively). Although STL remains the most frequent treatment choice for failures after RT in laryngeal carcinomas, SPL represents a valid option for selected patients with limited recurrence and can deliver good oncologic and functional results if performed according to careful indications.

Laparoscopic left liver lobectomy for hepatocellular carcinoma in a cirrhotic patient: a video report.

We present a video case of a 51-year-old man admitted to our surgical and liver transplantation unit for hepatocellular cancer (HCC). Patient has a HCV cirrhosis with portal hypertension and esophageal varices F1. Child Pugh score was B7 and model of end staged liver disease (MELD) was 11. Body mass index (BMI) was 26.7 and ASA score was 2. No previous abdominal surgery. According with our multidisciplinary group we suggest a laparoscopic left lobectomy for the patient. Pringle manoeuvre was not performed. Operation time was 193 min and blood loss estimation was 100 cc. No transfusion was required. Post-operative course was uneventful, grade I of Clavien-Dindo Classification. Patient was discharged in day 8. In our experience laparoscopic resection in cirrhotic liver should be performed in selected patients and in an experienced team.

External auditory canal ectopic atypical meningioma: A case report and brief literature review.

Meningiomas are tumours typically derived from the meningothelial cells of the arachnoid mater. They most often arise in intracranial, intraspinal, or orbital locations. Ectopic meningiomas, described as primary meningiomas with no intracranial involvement, are definitely unconventional. In fact, most of the extracranial meningiomas described in the literature, particularly in the outer ear, are effectively spreads of disease with primary intracranial localization. We describe a case of a primary external auditory canal meningioma with demonstrated absence of intracranial involvement, and we provide a full radiological, histological, immunohistochemical and molecular characterization of the lesion.

Exploring 6 years of colorectal cancer surgery in rural Italy: insights from 648 consecutive patients unveiling successes and challenges.

The multidisciplinary management of patients suffering from colorectal cancer (CRC) has significantly increased survival over the decades and surgery remains the only potentially curative option for it. However, despite the implementation of minimally invasive surgery and ERAS pathway, the overall morbidity and mortality remain quite high, especially in rural populations because of urban - rural disparities. The aim of the study is to analyze the characteristics and the surgical outcomes of a series of unselected CRC patients residing in two similar rural areas in Italy. A total of 648 consecutive patients of a median age of 73 years (IQR 64-81) was enrolled between 2017 and 2022 in a prospective database. Emergency admission (EA) was recorded in 221 patients (34.1%), and emergency surgery (ES) was required in 11.4% of the patients. Tumor resection and laparoscopic resection rates were 95.0% and 63.2%, respectively. The median length of stay was 8 days. The overall morbidity and mortality rates were 23.5% and 3.2%, respectively. EA was associated with increased median age (77.5 vs. 71 ys, p < 0.001), increased mean ASA Score (2.84 vs. 2.59; p = 0.002) and increased IV stage disease rate (25.3% vs. 11.5%, p < 0.001). EA was also associated with lower tumor resection rate (87.3% vs. 99.1%, p < 0.001), restorative resection rate (71.5 vs. 89.7%, p < 0.001), and laparoscopic resection rate (36.2 vs. 72.6%, p < 0.001). Increased mortality rates were associated with EA (7.2% vs. 1.2%, p < 0.001), ES (11.1% vs. 2.0%, p < 0.001) and age more than 80 years (5.8% vs. 1.9%, p < 0.001). In rural areas, high quality oncologic care can be delivered in CRC patients. However, the surgical outcomes are adversely affected by a still too high proportion of emergency presentation of elderly and frail patients that need additional intensive care supports beyond the surgical skill and alternative strategies for earlier detection of the disease.

Chronic pancreatitis and pancreatic lithiasis. State of the art.

Chronic pancreatitis and pancreatic lithiasis, isolated or associated, are infrequent diseases in western countries. They are linked to alcohol abuse, cigarette smoking, repeated episodes of acute pancreatitis and hereditary genetic factors. They are characterised by persistent or recurrent epigastric pain, digestive insufficiency, steatorrhoea, weight loss and secondary diabetes. They are easily diagnosed with CT and MRI ultrasound, but are difficult to treat. Medical therapy is symptomatic for diabetes and digestive failure. Invasive treatment is indicated only for pain that cannot be treated otherwise. For lithiasic forms, the therapeutic goal of removing stones can be achieved with shockwave and endoscopy, obtaining fragmentation and extraction of the stones. When this does not happen and these aids have proved ineffective, surgery must be used either as a partial or total resection of the afflicted pancreas, or as a derivation in the intestine of the pancreatic duct dilated and obstructed by Wirsung-jejunal anastomosis. These invasive treatments are effective in 80% of cases, but burdened with complications in 10% and relapses in 5%. KEY WORDS: Chronic Pancreatitis, Chronic Pain, Pancreatic Lithiasis.

Large retroperitoneal sarcoma invading the inferior vena cava successfully resected. Technical notes of two cases.

Retroperitoneal sarcomas are rare neoplasms . They frequently reach a very large size and invade adjacent organs before they are detected. Involvent of the inferior vena cava is uncommon. Distant metastases are a late feature. The mainstay of treatment is compartmental resection and contiguous organ resection. We report two cases of right-sided massive primary retroperitoneal leiomyosarcoma in pauci symptomatic women. In both cases treatment consisted of radical surgery. En bloc resection of the tumor and surrounding tissues and organs as well as part of the right wall of the subrenal IVC. To close the wall defect direct suture repair was used resulting in a reduced caliber but no hemodynamic sequelae or endoluminal thrombi. All the resection margins, including the inferior vena cava wall, were negative. The postoperative course was unremarkable and caval blood flow was optimal. The current gold standard treatment for retroperitoneal sarcoma is en bloc multivisceral resectionresection. KEY WORDS: Peritoneal sarcoma, Surgery, Vena cava.

Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis.

Introduction: Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results: Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion: Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

Genetics and Epigenetics of Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism (PHPT), characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. As opposed to parathyroid hyperplasia and adenomas, PC is associated with a poor prognosis, due to a commonly unmanageable hypercalcemia, which accounts for death in the majority of cases, and an overall survival rate of 78-85% and 49-70% at 5 and 10 years after diagnosis, respectively. No definitively effective therapies for PC are currently available. The mainly employed treatment for PC is the surgical removal of tumoral gland(s). Post-surgical persistent or recurrent disease manifest in about 50% of patients. The comprehension of genetic and epigenetic bases and molecular pathways that characterize parathyroid carcinogenesis is important to distinguish malignant PCs from benign adenomas, and to identify specific targets for novel therapies. Germline heterozygote inactivating mutations of the CDC73 tumor suppressor gene, with somatic loss of heterozygosity at 1q31.2 locus, account for about 50-75% of familial cases; over 75% of sporadic PCs harbor biallelic somatic inactivation/loss of CDC73. Recurrent mutations of the PRUNE2 gene, a recurrent mutation in the ADCK1 gene, genetic amplification of the CCND1 gene, alterations of the PI3K/AKT/mTOR signaling pathway, and modifications of microRNA expression profile and gene promoter methylation pattern have all been detected in PC. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of PC, in both familial and sporadic forms of this malignancy.

Estimating survival after salvage surgery for recurrent salivary gland cancers: Systematic review.

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty-five patients underwent salvage surgery (20.1%) and their 5-year mortality rate, overall survival and disease-free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow-up.