Intraoperative intraductal ultrasonography of the main pancreatic duct during pancreatoduodenectomy: technical description of a pilot series.

The intraoperative risk stratification during pancreatoduodenectomy is gaining increasing significance. The main pancreatic duct wall is of particular importance as it represents the element of anchor of the anastomotic stiches. This study aims to describe the safety, feasibility, and reproducibility of a novel intraductal ultrasonography of the main pancreatic (MPD)-Wirsung duct (IWU) during pancreatoduodenectomy (PD).A prospective series of 58 patients underwent PD with anastomosis between the MPD and the jejunum. Just before the reconstructive phase, the remaining pancreatic stump underwent complete IWU with definition of Wirsung thickness (WT) at the anastomotic site, using a radial ultrasound probe of 1.7 mm in diameter.No IWU-related complications were reported. The median WT of the MPD was 1.1 mm (SD 0.2). The rates of postoperative pancreatic fistula (POPF), major morbidity, and mortality were 17, 5, and 0%, respectively.The use of IWU during PD demonstrated safety and feasibility. IWU represents a new tool aimed at determining structural characteristics of the MPD that could impact on the surgical strategy of the pancreatic anastomosis. Further validation and comparative analysis with the current standard of care are warranted within a prospective controlled framework.

Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA): a binational multicenter randomized controlled trial.

BACKGROUND: Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, Surgery 52:205-22, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. METHODS/DESIGN: Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., Surgery 142:20-5, 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. DISCUSSION: PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente etal., Surgery 142:20-5, 2007; Bassi et al., Surgery 161:584-91, 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., Surgery 159:1013-22, 2016; Pratt et al., J Gastrointest Surg 10:1264-78, 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., Ann Surg 2022; Asbun and Stauffer, Surg Endosc 25:2643-9, 2011).

Progression from biochemical leak to pancreatic fistula after distal pancreatectomy. Don't cry over spilt amylase.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a frequent complication after distal pancreatectomy (DP), but its upgrading from biochemical leak (BL) still represents an unexplored phenomenon. This study aims at identifying risk factors of the clinical evolution from BL to grade-B POPF after DP. METHODS: Patients who underwent DP between 2015 and 2019 and who developed either BL (n = 89,56%) or BL upgraded to late B fistula (LB) after postoperative day 5 (n = 71,44%) were included. Preoperative, surgical, postoperative predictors were compared between the two groups. RESULTS: Patients with LB were significantly older (61 vs 56 years, P < 0.025) and received neoadjuvant chemotherapy more frequently (22.5% vs 8.5%,P = 0.017). Extended lymphadenectomy (52.8% vs 31.0%,P = 0.006), longer operative times (OT) (307 vs 250 min,P = 0.002), greater estimated blood loss (250 vs 150 ml, P = 0.021), and the appearance of purulent fluid in surgical drains (58.4% vs 21.1%; P < 0.001) were more frequently observed in LB group. Only purulent fluid in surgical drains and longer OT were confirmed as independent predictors of BL clinical progression. CONCLUSIONS: Purulent fluid from surgical drains should be suspicious of BL upgrading. Frail patients undergoing longer interventions may represent key targets of mitigation strategies to minimize the magnitude of an incipient fistula and its increase in morbidity.

The faith of non-surveilled pancreatic cysts: a bicentric retrospective study.

BACKGROUND: Incidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions. MATERIALS AND METHODS: A population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of "low risk" branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared. RESULTS: Overall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (≅ 1% and 2%, p = 0.589) and DSS (≅ 100% and 98%, p = 0.050). CONCLUSION: The "price to pay" for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol.

Actual malignancy risk of either operated or non-operated presumed mucinous cystic neoplasms of the pancreas under surveillance.

BACKGROUND: Despite the low malignant potential of pancreatic mucinous cystic neoplasms (MCNs), surgery is still performed. The aim of this pragmatic study was to assess the outcome of surgery and surveillance for patients presenting with a presumed MCN at the first evaluation. METHODS: Data for patients with a presumed MCN observed from 2000 to 2016 at the Verona Pancreas Institute and San Raffaele Hospital were extracted from prospective databases. The endpoints were risk of malignancy at pathology and rate of misdiagnosis for the surgical series, expressed as an odds ratio (OR) with 95 per cent confidence interval, and disease-specific survival (DSS) for the surveillance cohort investigated by the Kaplan-Meier method. RESULTS: A total of 424 patients were identified. In the surgical series (229 patients), the rate of misdiagnosis was 19.2 per cent. The rate of malignant MCNs was 10.9 per cent (25 patients). The overall rate of malignancy, including misdiagnoses, was 11.3 per cent (26 patients). Predictors of malignancy were mural nodules (OR 27.75, 95 per cent c.i. 4.44-173.61; P < 0.001), size at least 50 mm (OR 13.39, 2.01 to 89.47; P = 0.007), and carbohydrate antigen 19.9 level (OR 3.98, 1.19 to 13.30; P = 0.025). In the absence of mural nodules and enhancing walls, none of the resected presumed MCNs smaller than 50 mm were malignant. Only patients with high-risk stigmata undergoing surgery experienced a significantly reduced 5-year DSS compared with all other patients (88 versus 100 per cent; P = 0.031). CONCLUSION: Presumed MCNs with mural nodules, enhancing walls or cysts of 50 mm or larger should be considered for upfront surgical resection owing to the high risk of malignancy. In the absence of these features, the incidence of malignancy is negligible, favouring surveillance in selected patients given the low risk of malignancy and the high rate of misdiagnosis. LAY SUMMARY: Malignant degeneration of presumed pancreatic mucinous cystic neoplasms takes several years, if it occurs at all. Mural nodules, enhancing walls or cysts of 50 mm or larger call for surgical resection owing to an increased risk of malignancy; otherwise, surveillance seems a good option.

Malignant degeneration of presumed pancreatic mucinous cystic neoplasms takes several years, if it occurs at all. Mural nodules, enhancing walls or cysts of 50 mm or larger call for surgical resection owing to an increased risk of malignancy; otherwise, surveillance seems a good option.

Systematic review and meta-analysis of observational studies on BD-IPMNS progression to malignancy.

BACKGROUND: The vast majority of presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are referred to a surveillance program due to the relatively low risk of malignancy. We aim to evaluate all available data from observational studies focused on the risks of BD-IPMN progression and malignancy to provide vital insights into its management in clinical practice. METHODS: A comprehensive search was conducted at PubMed, Cochrane, Web of Science and Embase for observational studies published before January 1st, 2020. The progression of BD-IPMN was defined as the development of worrisome features (WFs) or high-risk stigmata (HRS) during surveillance. Overall malignancy was defined as all malignancies, such as malignant IPMN, concomitant pancreatic ductal adenocarcinoma (PDAC) and other malignancies, including BD-IPMN with high-grade sec. Baltimore consensus 2015 or BD-IPMN with high-grade dysplasia (carcinoma in situ) sec. WHO 2010. A meta-analysis was performed to investigate the presence of a mural nodule as a possible predictor of malignancy. RESULTS: Twenty-four studies were included, with a total of 8941 patients with a presumed BD-IPMN. The progression rate was 20.2%, and 11.8% underwent surgery, 29.5% of whom showed malignancy at the final pathology. Of those, 78% had malignant IPMNs, and 22% had concomitant pancreatic cancer. Overall, 0.5% had distant metastasis. The meta-analysis showed that the risk of malignancy in the presence of a mural nodule >5 mm had a RR of 5.457 (95% CI 1.404-21.353), while a nonenhancing mural nodule or an enhancing mural nodule < 5 mm had a RR of 5.286 (95% CI 1.805-15.481) of harboring malignancy. CONCLUSION: Most presumed BD-IPMNs entering surveillance do not become malignant. Of those submitted to surgery, concomitant PDAC adds to the overall risk of detecting malignancy.

Risk of malignancy in small pancreatic cysts decreases over time.

BACKGROUND: Pancreatic cysts <15 mm without worrisome features have practically no risk of malignancy at the time of diagnosis but this can change over time. Optimal duration of follow-up is a matter of debate. We evaluated predictors of malignancy and attempted to identify a time to safely discontinue surveillance. METHODS: Bi-centric study utilizing prospectively collected databases of patients with pancreatic cysts measuring <15 mm and without worrisome features who underwent surveillance at the Massachusetts General Hospital (1988-2017) and at the University of Verona Hospital Trust (2000-2016). The risk of malignant transformation was assessed using the Kaplan-Meier method and parametric survival models, and predictors of malignancy were evaluated using Cox regression. RESULTS: 806 patients were identified. Median follow-up was 58 months (6-347). Over time, 58 (7.2%) cysts were resected and of those, 11 had high grade dysplasia (HGD) or invasive cancer. Three additional patients had unresectable cancer for a total rate of malignancy of 1.7%. Predictors of development of malignancy included an increase in size ≥2.5 mm/year (HR = 29.54, 95% CI: 9.39-92.91, P < 0.001) and the development of worrisome features (HR = 9.17, 95% CI: 2.99-28.10, P = 0.001). Comparison of parametric survival models suggested that the risk of malignancy decreased after three years of surveillance and was lower than 0.2% after five years. CONCLUSIONS: Pancreatic cysts <15  mm at the time of diagnosis have a very low risk of malignant transformation. Our findings indicate the risk decreases over time. Size increase of ≥2.5 mm/year is the strongest predictor of malignancy.

Nonlinear Thermoelectricity with Electron-Hole Symmetric Systems.

In the linear regime, thermoelectric effects between two conductors are possible only in the presence of an explicit breaking of the electron-hole symmetry. We consider a tunnel junction between two electrodes and show that this condition is no longer required outside the linear regime. In particular, we demonstrate that a thermally biased junction can display an absolute negative conductance, and hence thermoelectric power, at a small but finite voltage bias, provided that the density of states of one of the electrodes is gapped and the other is monotonically decreasing. We consider a prototype system that fulfills these requirements, namely, a tunnel junction between two different superconductors where the Josephson contribution is suppressed. We discuss this nonlinear thermoelectric effect based on the spontaneous breaking of electron-hole symmetry in the system, characterize its main figures of merit, and discuss some possible applications.

Use of an intraoperative wound protector to prevent surgical-site infection after pancreatoduodenectomy: randomized clinical trial.

BACKGROUND: Surgical-site infection (SSI) increases treatment costs, duration of hospital stay and readmission rate after pancreatic surgery. This study aimed to assess whether a wound protector could reduce the risk of superficial incisional SSI after pancreatoduodenectomy. METHODS: This RCT included patients undergoing pancreatoduodenectomy at Verona University Hospital, between 2017 and 2018. The experimental group had a dual-ring wound protector, whereas the control group had standard surgical drapes. The groups were stratified by preoperative biliary stent placement. The primary outcome was the overall rate of superficial SSI. RESULTS: An interim analysis was conducted after 212 patients had been enrolled; 22 patients (10·4 per cent) were excluded owing to inability to complete the pancreatoduodenectomy, or the need for postoperative reintervention. Some 94 patients (49·5 per cent) had a wound protector and 96 (50·5 per cent) had standard drapes. There were no differences between groups in demographics, or in intraoperative findings, pathological data or surgical outcomes. The overall superficial SSI rate was 7·4 per cent, which did not differ between groups (7 per cent in each group; P = 0·585). Subanalysis of patients with a preoperative biliary stent showed a similar outcome (superficial SSI rate 9 versus 8 per cent with wound protector versus surgical drapes respectively; P = 0·536). The trial was stopped prematurely on the grounds of futility. CONCLUSION: Use of a wound protector did not reduce the rate of superficial SSI after pancreatoduodenectomy. Registration number: NCT03820648 (http://www.clinicaltrials.gov).

ANTECEDENTES: La infección de la herida quirúrgica (surgical-site infection, SSI), especialmente de la incisión, aumenta sobremanera los costes del tratamiento, la duración de la estancia y la tasa de reingresos en la cirugía de páncreas. En los últimos años se han introducido los protectores de las heridas (wound protectors, WP) con la intención de reducir la tasa de SSI. Este estudio tuvo como objetivo evaluar si un WP podría reducir la incidencia de la SSI superficial de la incisión (superficial incisional surgical-site infection, SI-SSI) en pacientes sometidos a duodenopancreatectomía cefálica (pancreaticoduodenectomy, PD). MÉTODOS: Ensayo aleatorizado controlado en el que se incluyeron los pacientes a los que se realizó una PD en la Universidad de Verona entre 2017 y 2018. En el grupo experimental se utilizó un WP de doble anillo, mientras que el grupo control se utilizaron tallas quirúrgicas convencionales (standard drape, SD). Los grupos se estratificaron también según la colocación preoperatoria de una prótesis biliar. RESULTADOS: Se incluyeron 212 pacientes, de los que 22 (10%) abandonaron el estudio debido a la imposibilidad de realizar la DP o a la necesidad de una reintervención durante el curso postoperatorio. Los pacientes se dividieron en 94 (49%) en el grupo WP y 96 (51%) en el grupo SD. No se detectaron diferencias entre grupos en cuanto a las variables demográficas y a los resultados intraoperatorios, patológicos o quirúrgicos. La tasa global de SI-SSI fue del 7,4%, que no difirió entre los grupos (WP 7,5% versus SD 7,3%, P = 0,585). Teniendo en cuenta los resultados descritos, se cumplieron los criterios de futilidad del análisis y el ensayo se interrumpió prematuramente. CONCLUSIÓN: En el entorno de un centro de alto volumen, la WP por si sola no redujo la tasa de SI-SSI. Cabría plantear su utilización dentro de un programa multimodal, que debería incluir un replanteamiento interno de la institución encaminado a la reducción de complicaciones infecciosas.

Branch Duct Intraductal Papillary Mucinous Neoplasms: Recommendations for Follow-Up and Surgery.

BACKGROUND AND AIMS: Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up. MATERIALS AND METHODS: Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms. RESULTS: The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases. CONCLUSION: Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.

Pancreaticoduodenectomy for paraduodenal pancreatitis is associated with a higher incidence of diabetes but a similar quality of life and pain control when compared to medical treatment.

BACKGROUND: Paraduodenal pancreatitis is a focal form of chronic pancreatitis that affects the groove area between the duodenum and the head of the pancreas. Consensus regarding surgical or nonsurgical management as the best treatment option is still lacking. METHODS: We retrospectively evaluated all patients managed for PP at The Pancreas Institute of the University Hospital Trust of Verona from 1990 to 2017. The outcomes of surgical vs. medical treatment with regard to pain control, quality of life and pancreatic insufficiency were evaluated through specific questionnaires. RESULTS: The final study population consisted of 75 patients: 62.6% underwent surgery, and 37.4% were managed without surgery. All surgical procedures consisted of pancreaticoduodenectomy. The median follow-up from the diagnosis of paraduodenal pancreatitis was 60 (12-240) months. Patients who underwent surgery experienced a similar incidence of steatorrhea (44.7 vs. 52.6%; p = 0.4) but a significantly higher incidence of diabetes (59.6 vs. 10.7%; p < 0.01) when compared to those managed without surgery. There was no difference in terms of reported chronic pain (Graded Chronic Pain Scale, median 0 vs. 1; p = 0.1) and quality of life (Pancreatitis QoL Instrument, median 82 vs. 79; p = 0.2). However, surgical patients reported a worse level of self-care activities associated with glycemic control (Diabetes Self-Management Questionnaire, median 20 vs. 28, p = 0.02). CONCLUSION: In patients affected by paraduodenal pancreatitis, surgery and medical therapy seem to obtain similar results in terms of quality of life and pain control. However, surgery is associated with an increased prevalence of postoperative diabetes with consequent relevant issues with self-care management. Surgery should be considered only in selected patients after adequate medical treatment.

Correlation between appearance of the retroportal fat plane at preoperative CT and pathology findings in resected adenocarcinoma of the pancreatic head.

AIM: To correlate the appearance of the retroportal fat plane at preoperative computed tomography (CT) and the pathology findings in resected adenocarcinoma of the pancreatic head (PDAC). MATERIAL AND METHODS: Forty-eight patients with resected PDAC of the pancreatic head were included (24 men, 24 women, mean age 63 years, median BMI 24.1). All patients underwent CT <30 days before surgery. The state of the retroperitoneal resection margin and the presence of lymphatic or perineural invasion were obtained from pathology reports. CT images were reviewed independently by two radiologists for assessment of the retroportal fat plane and graded in two categories (clear/effaced). Inter-reader discrepancies were solved in consensus. Interobserver agreement was calculated and Fisher's test was used to assess the correlation between CT and pathology findings. Visceral fat areas were measured and correlated with CT findings. RESULTS: A clear retroportal fat plane was significantly associated with a negative retroperitoneal margin at pathology with 100% specificity and PPV (p=0.0001). No association was observed between the appearance of the fat plane at CT and the presence of lymphatic or perineural invasion (p=ns). Interobserver agreement for retroportal fat plane evaluation was good (0.741). False-positive cases had a significantly lower visceral fat area than the correctly classified patients (p=0.0480). CONCLUSIONS: A clear retroportal fat plane is significantly associated with negative retroperitoneal resection margins at pathology. The lack of visceral adipose tissue can lead to overestimation of retroportal fat plane involvement at preoperative CT.

Importance of main pancreatic duct dilatation in IPMN undergoing surveillance.

BACKGROUND: The association between risk of pancreatic cancer and a dilated main pancreatic duct (MPD) in intraductal papillary mucinous neoplasm (IPMN) is debated. The aim of this study was to assess the role of MPD size in predicting pancreatic cancer in resected IPMNs and those kept under surveillance. METHODS: All patients with IPMN referred to the Pancreas Institute, University of Verona Hospital Trust, from 2006 to 2016 were included. The primary endpoint was the occurrence of malignancy detected at surgery or during follow-up. RESULTS: The final cohort consisted of 1688 patients with a median follow-up of 60 months. Main pancreatic duct dilatation was associated with other features of malignancy in both the resected and surveillance groups. In patients who underwent resection, only a MPD of at least 10 mm was an independent predictor of malignancy. In patients kept under surveillance, MPD dilatation was not associated with malignancy. Fifteen of 71 patients (21 per cent) with malignancy in the resection cohort had a dilated MPD alone, whereas only one of 30 (3 per cent) under surveillance with MPD dilatation alone developed malignancy. Patients with a dilated MPD and other worrisome features had an increased 5-year cumulative incidence of malignancy compared with those with a non-dilated duct (11 versus 1·2 per cent; P < 0·001); however, the risk of malignancy was not significantly increased in patients with a dilated MPD alone (4 versus 1·2 per cent; P = 0·448). CONCLUSION: In patients under surveillance, a dilated MPD alone was not associated with an increased incidence of malignancy in IPMN.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Sonochemical synthesis of versatile hydrophilic magnetite nanoparticles.

Hydrophilic magnetite nanoparticles in the size range 30-10nm are easily and rapidly prepared under ultrasonic irradiation of Fe(OH)(2) in di- and tri-ethylene glycol/water solution with volume ratio varying between 7:3 and 3:7. Structural (XRD) and morphological (SEM) characterization reveal good crystalline and homogeneous particles whereas, when solvothermally prepared, the particles are inhomogeneous and aggregated. The sonochemically prepared particles are versatile, i.e. well suited to covalently bind molecules because of the free glycol hydroxylic groups on their surface or exchange the diethylene or triethylene glycol ligand. They can be easily transferred in hydrophobic solvents too. Room-temperature magnetic hysteresis properties measured by means of Vibrating Sample Magnetometer (VSM) display a nearly superparamagnetic character. The sonochemical preparation is easily scalable to meet industrial demand.