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Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers., Summary Background Data: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection., Methods: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998)., Results: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%., Conclusion: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Background: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD)., Methods: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402)., Results: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001)., Conclusion: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: With continued technical advances in surgical instruments and growing expertise, several surgeons have performed laparoscopic pylorus preserving pancreaticoduodenectomy (L-PPPD) safely with good results, and the laparoscopic approach is being performed more frequently. We performed over 100 cases of L-PPPD and compared their outcomes to those of open PPPD (O-PPPD) using the large sample size. The aim of the present study was to evaluate the safety and feasibility of L-PPPD compared with O-PPPD., Methods: From September 2012 to June 2017, PPPD was performed for 217 patients at Yonsei University Severance Hospital by a single surgeon. Patients were divided into two groups: those who underwent O-PPPD (n = 113) and those who underwent L-PPPD (n = 104). We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographic and surgical outcomes. We also reviewed all previous studies of more than 100 cases., Results: The L-PPPD group had lesser intraoperative blood loss than the O-PPPD group (548.1 ml vs. 244.7 ml; p < 0.001). Both groups showed similar rates of negative resection margins (99.1% vs. 96.2%; p = 0.196). Overall complication rates did not differ significantly between O-PPPD and L-PPPD (39.8% vs. 35.6%; p = 0.519). The clinically relevant postoperative pancreatic fistula (POPF) rates in the O-PPPD and L-PPPD groups were 18.8% and 13.5%, respectively (p = 0.311). There was no difference in 30- and 90-day mortality rates between the two groups (p = 0.479). Similar results were obtained after PSM analysis., Conclusions: L-PPPD can be a good alternative option for well-selected patients with periampullary lesions requiring PPPD.

Objective: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD)., Background: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative., Methods: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches., Results: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases., Conclusion: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Background: The purpose of this study was to validate the predictive value of the oncologic outcome in addition to the validation of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator in patients treated with pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD) for pancreatic head cancer., Methods: From June 2005 to December 2014, 199 patients underwent PD or PPPD for pancreatic head cancer. Medical records were retrospectively reviewed for investigating general patient characteristics and any comorbid diseases. The calculated perioperative complication risks from the ACS NSQIP calculator were compared with observed complication rates. In a propensity score matching analysis, disease-free survival (DFS) and overall survival (OS) were estimated according to calculated severe complication rate (CSCR)., Results: The CSCR > 17.9% (n = 69) and CSCR < 17.9% (n = 130) groups were significantly different considering number of the retrieved lymph nodes (22.95 ± 14.0 vs 18.80 ± 10.1, p = 0.029), histologic grade (p = 0.0235), and incidence of lymphovascular invasion (p = 0.026). The CSCR < 17.9% group had longer DFS (17.0 vs. 11.0 months, p = 0.015), but the OS was similar between the groups (39.0 vs. 23.0 months, p = 0.48). In the 1:2 propensity score analysis, the CSCR < 17.9% group had longer DFS and OS (DFS 26.0 vs. 11.0 months, p = 0.009; OS 44.0 vs. 26.0 months, p = 0.023)., Conclusion: The ACS NSQIP surgical risk calculator predicts surgical risk in patients with pancreatic head cancer who undergo PD or PPPD. Furthermore, this tool can help predict the prognosis of surgically treated pancreatic head cancer.

Background: During laparoscopic pancreaticoduodenectomy (LPD), dissecting uncinate process from the superior mesenteric artery (SMA) will determine one of the important surgical margins (retroperitoneal margin) for predicting oncological outcomes and the quality of LPD. However, clear identification of the division line for retroperitoneal margin is not easy as the uncinate process of the pancreas is anatomically very close to SMA and intermingled with the nerve plexus and soft tissues around SMA. In this study, we present data regarding the potential usefulness of indocyanine green (ICG)-enhanced approach in obtaining retroperitoneal margin during LPD., Methods: From January to September 2017, medical records of patients who underwent LPD for periampullary pathological conditions were retrospectively reviewed. ICG (5 mg/2 cm 3 ) was prepared and intravenously injected when dissecting uncinate process of the pancreas. Perioperative outcomes, including gender, age, diagnosis, body mass index, operation time, estimated blood loss, transfusion, presence of postoperative pancreatic fistulas (POPFs), and length of hospital stay, were evaluated., Results: During the study period, a total of 37 patients underwent LPD for periampullary pathological lesions. Among them, ICG-enhanced dissection of uncinate process of the pancreas was applied in 10 patients (27%). All patients were able to obtain margin-negative resection. There were no significant differences between the perioperative outcomes of patients who did and did not undergo ICG-enhanced approach., Discussion: ICG perfusion-based laparoscopic dissection of retroperitoneal margin is feasible and safe in LPD. This intraoperative visual difference can provide the surgeon with very helpful real-time visual information. Further study is mandatory.

Background: Nasogastric tube placement after abdominal surgery has been a standard procedure for many decades. In pancreatoduodenectomy, delayed gastric emptying (DGE) is still a leading postoperative complication, often resulting in patient anxiety or depression and prolonged hospital stays. Such complications have led many surgeons to prefer postoperative nasogastric decompression because of the greater risk of DGE. Therefore, the goal of this study was to evaluate the DGE and perioperative outcomes after pylorus-preserving pancreatoduodenectomy (PPPD) with or without routine gastrostomy., Methods: From May 2009 to December 2014, 228 patients underwent PPPD at the Department of Surgery, Gangnam Severance Hospital, Yonsei University. The first cohort of 116 patients underwent surgery before June 2012 and uniformly underwent gastric decompression as a part of postoperative management. The second cohort of 112 patients underwent operation after July 2012, and gastric decompression was selectively used to facilitate exposure during operation and was removed in the operating room at the end of surgery. We evaluated DGE incidence, time to dietary tolerance, length of hospital stay, and postoperative gastric tube reinsertion rates., Results: Gastric re-decompression was necessary in 38 patients (16.7 %), and there was a significant difference between the two groups (p = 0.006). Eleven (9.8 %) patients in the no-tube gastrostomy group required nasogastric tube reinsertion, and 27 (23.3 %) in the routine gastrostomy group required that the gastrostomy tube be re-drainage. There were no statistically significant differences in the frequency or severity of complications such as delayed gastric emptying or pancreatic leakage., Conclusions: Our study demonstrates that routine postoperative gastric decompression can be safely avoided in patients who undergo PPPD.

Background: When bile duct cancer recurs after surgery, treatment options are limited. This study examines the usefulness of reoperative pancreaticoduodenectomy for recurrent cancer after initial segmental bile duct resection., Methods: Six patients (5 males, 1 females; median age 65 years) who underwent pancreaticoduodenectomy for recurrent remnant bile duct cancer following segmental bile duct resection were included: 4 underwent surgery at Severance Hospital and 2 at Gangnam Severance Hospital from January 2000 to December 2013. Medical records data were retrospectively reviewed, including demographics, type of first and second surgery, radicality of resection, TNM stage, adjuvant treatments, complications, and survival. Kaplan-Meier curves were used to analyze survival., Results: The median interval between operations was 57 (range 7-95) months. Median operation time was 6.9 (range 5.2-12.8) h, blood loss was 400 (range 50-1170) mL, intensive care unit stay was 1 (range 1-2) day, and postoperative hospital stay was 33 (range 15-55) days. No patient died. Four had severe complications. The median survival after pancreaticoduodenectomy was 16 (range 5-89) months. Four patients had recurrence. T stage, N stage, and resection radicality influenced survival., Conclusion: Pancreaticoduodenectomy is reasonable for recurrent remnant bile duct cancer following segmental bile duct resection, particularly for patients with no distant metastasis, locally confined recurrence, and good general condition.

Objective: To prospectively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer., Background: Despite randomized controlled trials on the extent of surgery in pancreatic cancer, attempts have been made to perform more extended resections., Methods: A total of 244 patients were enrolled; of these, 200 were randomized to undergo standard resection or extended resection, with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis. We evaluated 167 patients from 7 centers who fulfilled all of the required criteria., Result: Operation time was longer and estimated blood loss was higher in the extended resection group than in the standard resection group, but the R0 resection rate was comparable. The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the standard resection group (33.7 vs 17.3; P < 0.001). The morbidity rate was slightly higher in the extended resection group than in the standard resection group. Two patients in the extended resection group died in hospital. Median survival after R0 resection was similar in the extended resection and standard resection groups (18.0 vs 19.0 months; P = 0.239) regardless of lymph node metastasis. Adjuvant chemoradiation had a positive impact on overall survival., Conclusions: This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)?

Introduction: The measurement of fecal elastas-1 in stools is a sensitive and relatively inexpensive noninvasive test. The aim of this study was to study fecal elastase levels in patients who develop pancreatic leakage after pancreaticoduodenectomy (PD) to determine if fecal elastase level can be used to predict patients at high risk for pancreatic leakage after PD., Methods: Pancreatic function was considered normal when fecal elastase-1 concentration exceeded 200 μg/g feces and moderately or severely insufficient when fecal elastas-1 concentration was less than 200 μg/g feces., Results: Of 123 patients who underwent PD, 67 (54.5%) showed fecal elastase-1 levels less than 200 μg/g, indicating moderate or severe pancreatic insufficiency. Pancreas texture, pathology origin, and level of γ-glutamyl transferase (r-GT) were significantly correlated with fecal elastas-1 level. On univariate analysis, the incidence of pancreatic leakage was significantly greater in the group with normal fecal elastase-1 level (≥200 μg/g), pathologic origin (bile duct/ampulla/duodenum), and soft pancreas texture. In multivariate analysis, normal fecal elastase-1 level (≥200 μg/g) and soft pancreatic texture were identified as independent factors for pancreatic leakage., Conclusions: Fecal elastase-1 is the most simple and objective method for predicting pancreatic leakage after PD., (© 2013 Wiley Periodicals, Inc.)

Background: Chyle leakage is a rare complication of pancreaticoduodenectomy (PD), and its association with pancreatic fistula has not been established. The aim of this study was to (1) evaluate the incidence, management, and risk factors of chyle leakage after PD; (2) determine if there is a relation between chyle leakage and diagnosis of pancreatic fistula; and (3) predict chyle leakage with drainage volume early., Methods: A total of 222 patients underwent PD or pylorus-preserving PD. We used the clinical database registry system of the Gangnam Severance Hospital, Yonsei University Health System to establish a retrospective cohort with clinicopathologic data., Results: Altogether, 24 patients (10.8 %) developed chyle leakage. Chyle leakage was identified at a median 5 days after surgery and a mean 2 days after enteral intake. The mean drain triglyceride level was 315 mg/dl. Early enteral intake was independently associated with chyle leakage. Chyle leakage was inversely correlated with a diagnosis of pancreatic fistula with marginal significance (odds ratio 0.27; 95 % confidence interval 0.66-1.09). The receiver operating characteristic curve of the volume on postoperative day 4 demonstrated an area under the curve of 0.740 (p = 0.0001). Drainage >335 ml indicated possible chyle leakage., Conclusions: Chyle leakage after PD is associated with early enteral intake. It was inversely correlated with a diagnosis of pancreatic fistula because of the dilution effect of drainage volume on the concentration of drained amylase. Because early diagnosis helps with appropriate management, prediction/suspicion of chyle leakage based on drainage volume may be useful.

Background: Obesity is associated with perioperative complications and has been considered a risk factor for surgical outcomes of patients undergoing abdominal surgery. The aim of this study is to evaluate the impact of the amount of visceral fat on postoperative morbidity of patients who underwent pancreaticoduodenectomy (PD)., Methods: We reviewed 181 patients who underwent surgery for periampullary lesions at the Department of Surgery, Gangnam Severance Hospital, Yonsei University Health System between January 2003 and June 2010. The visceral fat area (VFA) and subcutaneous fat area were calculated by computed tomography software., Results: The mean body mass index (BMI) was 23.4 kg/m(2) (±3.1 kg/m(2)), and the mean VFA was 94.4 cm(2) (±49.5 cm(2)). The mean intraoperative blood loss, and the incidence of clinically relevant pancreatic fistula (grade B/C) and clinically relevant delayed gastric emptying (grade B/C) were significantly higher in the high-VFA group (≥100 cm(2)). In univariate analysis, the incidence of clinically relevant pancreatic fistula (grade B/C) was significantly higher in the high-BMI group (≥25 kg/m(2)), the high-VFA group(≥100 cm(2)), the large intraoperative blood loss and transfusion group, and in patients with pathology of nonpancreatic origin (ampulla, bile duct, or duodenum). In multivariate analysis, the high-VFA group (≥100 cm(2)) and patients with pathology of nonpancreatic origin were identified as independent factors for clinically relevant pancreatic fistula., Conclusion: VFA is a better indicator for the development of pancreatic fistula after PD than BMI. High VFA (≥100 cm(2)) is a risk factor for developing a pancreatic fistula after PD.

The benefits of early enteral feeding (EEN) have been demonstrated in gastrointestinal surgery. But, the impact of EEN has not been elucidated yet. We assessed the postoperative nutritional status of patients who had undergone pancreaticoduodenectomy (PD) according to the postoperative nutritional method and compared the clinical outcomes of two methods. A prospective randomized trial was undertaken following PD. Patients were randomly divided into two groups; the EEN group received the postoperative enteral feed and the control group received the postoperative total parenteral nutrition (TPN) management. Thirty-eight patients were included in our analyses. The first day of bowel movement and time to take a normal soft diet was significantly shorter in EEN group than in TPN group. Prealbumin and transferrin were significantly reduced on post-operative day (POD) 7 and were slowly recovered until POD 90 in the TPN group than in the EEN group. EEN group rapidly recovered weight after POD 21 whereas it was gradually decreased in TPN group until POD 90. EEN after PD is associated with preservation of weight compared with TPN and impact on recovery of digestive function after PD.

Purpose: Accurate indications and the extent of surgery for branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas are still debatable. In particular, small tumor is located at the head portion of pancreas presents a dilemma. The purpose of this study is to compare the efficacy of enucleation (EN) with that of pancreaticoduodenectomy (PD) in patients with small (2 cm

Context: Several surgical complications are related to obesity., Objective: This study evaluated the impact of obesity on pancreatic fistula after pancreaticoduodenectomy., Design: We retrospectively reviewed the medical records of 159 patients who underwent pancreaticoduodenectomy between October 2002 and December 2008., Setting: The patients were divided according to the body mass index as obese (body mass index equal to, or greater than, 25 kg/m(2)), or normal (body mass index less than 25 kg/m(2))., Methods: Univariate and multivariate analyses were applied. Two-tailed P values less than 0.05 were considered as significant., Results: Forty-six patients (28.9%) were obese and 113 patients (71.1%) were normal-weight. Obese group had a significantly higher incidence of pancreatic fistula and a greater amount of intraoperative blood loss. Other surgical complications were not significantly different between the two groups. Multivariate analysis found obesity, small pancreatic duct size (less than, or equal to, 3 mm), intraoperative blood loss, and combined resection as significant factors affecting pancreatic fistula., Conclusions: Obese patients have an increased risk for pancreatic fistula after pancreaticoduodenectomy.

Background: Delayed gastric emptying (DGE) is one of the most common complications after pancreatoduodenectomy (PD). Because an objective, universally accepted definition of DGE does not yet exist, it is impossible to compare complication rates and outcomes of new operative approaches, operative techniques, and clinical trials. The International Study Group of Pancreatic Surgery (ISGPS) has proposed a universal classification for DGE based on clinical outcomes, but this classification has not been tested rigorously and applied to clinical data. Therefore, the aim of this study was to analyze our experience and to identify predictive factors for DGE by applying the ISGPS classification at a high-volume hospital., Methods: From October 2002 to December 2007, 129 consecutive patients underwent PD at the Department of Surgery, Yonsei University Medical Center. The severity of DGE was determined according to the ISGPS classification, and risk factors were evaluated retrospectively., Results: The overall incidence of DGE was 33.3%, with 16 (12.4%) patients having grade A, 14 (10.9%) grade B, and 13 (10.1%) grade C. Clinical outcomes worsened progressively as clinical relevant DGE increased. In multivariate analysis, clinically relevant pancreatic fistula (grade B/C) and patients with benign pathology were identified as independent factors for DGE., Conclusion: Pancreatic leakage is a serious complication after PD and is also associated with DGE. The ISGPS classification is a clear and useful tool to assess clinical outcomes.

Background: The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN., Methods: We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea., Results: Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor 2 cm, >25%., Conclusions: Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of