Correlation between Angiotensin Inhibitor Administration and Longer Survival in Patients Who Underwent Curative Resection for Pancreatic Cancer.

PURPOSE: The microenvironment of pancreatic ductal adenocarcinoma (PDAC) with extensive desmoplastic stroma contributes to aggressive cancer behavior. Angiotensin system inhibitors (ASIs) reduce stromal fibrosis and are a promising therapeutic strategy. The purpose of this study was to examine how ASIs affected the oncological results of patients who had their PDAC removed. MATERIALS AND METHODS: A retrospective assessment was conducted on the clinicopathological and survival data of patients who received curative resection for PDAC at Severance Hospital between January 2012 and December 2019. RESULTS: A total of 410 participants (228 male and 182 female), with a median follow-up period of 12.8 months, were included in this study. Patients were divided into three groups, based on ASI use and history of hypertension: group 1, normotensive and never used ASI (n=210, 51.2%); group 2, ASI non-users with hypertension (n=50, 12.2%); and group 3, ASI users with hypertension (n=150, 36.6%). The three groups did not differ significantly in terms of age, sex, kind of operation, T and N stages, or adjuvant and neoadjuvant therapy. Moreover, there was no discernible difference in disease-free survival between those who used ASI and those who did not (p=0.636). The 5-year overall survival (OS) rates in groups 1, 2, and 3 were 52.6%, 32.3%, and 38.0%, respectively. However, the OS rate of ASI users was remarkably higher than that of non-users (p=0.016). CONCLUSION: In patients with resected PDAC, ASI is linked to longer survival rates. Furthermore, for individuals with hypertension, ASI in conjunction with conventional chemotherapy may be an easy and successful treatment option.

The Revo-i Robotic Surgical System in Advanced Pancreatic Surgery: A Second Non-Randomized Clinical Trial and Comparative Analysis to the da Vinci™ System.

PURPOSE: Numerous robot-assisted pancreatic surgery are being performed worldwide. This study aimed to evaluate the feasibility and safety of the Revo-i robot system (Meerecompany, Seoul, Republic of Korea) for advanced pancreatic surgery, and also compare this new system with the existing da Vinci™ robot system (Intuitive Surgical, Sunnyvale, CA, USA) in the context of robot-assisted pancreaticoduodenectomy (RPD). MATERIALS AND METHODS: This study was a one-armed prospective clinical trial that assessed the Revo-i robot system for advanced pancreatic surgery. Ten patients aged 30 to 73 years were enrolled between December 2019 and August 2020. Postoperative outcomes were retrospectively compared with those of the da Vinci™ surgical system. From March 2017 to August 2020, a total of 47 patients who underwent RPD were analyzed retrospectively. RESULTS: In the prospective clinical trial, pancreaticoduodenectomy was performed in nine patients and one patient underwent central pancreatectomy. Among the 10 study participants, the incidence of major complications was 0% in hospital stay. There were eight postoperative pancreatic fistula (POPF) biochemical leaks (80%). In the retrospective analysis that compared the Revo-i and da Vinci™ robotic systems, 10 patients underwent Revo-i RPD and 37 patients underwent da Vinci™ RPD, with no significant differences in complication or POPF incidence rates between the two groups (p=0.695, p=0.317). CONCLUSION: In this single-arm prospective study with short-term follow-up at a single institution, the Revo-i robotic surgical system was safe and effective for advanced pancreatic surgery. Revo-i RPD is comparable to the da Vinci™ RPD and is expected to have wide clinical application.

Insulin-like growth factor binding protein-3 induces senescence by inhibiting telomerase activity in MCF-7 breast cancer cells.

Insulin-like growth factor binding protein-3 (IGFBP-3) has been known to inhibit cell proliferation and exert tumor-suppressing effects depending on the cell type. In this study, we aimed to show that IGFBP-3 induces cellular senescence via suppression of the telomerase activity, thereby inhibiting MCF-7 breast cancer cell proliferation. We found that the induction of IGFBP-3 in MCF-7 cells enhanced the loss of cell viability. Flow cytometry revealed a higher percentage of non-cycling cells among IGFBP-3-expressing cells than among controls. IGFBP-3 induction also resulted in morphological alterations, such as a flattened cytoplasm and increased granularity, suggesting that IGFBP-3 induces a senescence-like phenotype. The percentage of IGFBP-3 expressing cells with senescence-associated ß-galactosidase activity was 3.4 times higher than control cells. Telomeric repeat amplification and real-time PCR showed that IGFBP-3 decreased telomerase activity by reducing the levels of the RNA component (hTR) and catalytic protein component with reverse transcriptase activity (hTERT) of telomerase in a dose-dependent manner. These results suggest that IGFBP-3 is a negative regulator of MCF-7 breast cancer cell growth by inducing senescence through telomerase suppression.

Regular Cannabis Use During the First Year of the Pandemic: Studying Trajectories Rather Than Prevalence.

INTRODUCTION: Cannabis use in the U.S. rose early in the COVID-19 pandemic, but it is unclear whether that rise was temporary or permanent. This study estimated the nature and sociodemographic correlates of U.S. adult subpopulations regularly using cannabis by examining weekly trajectories of use during the first year of the pandemic. METHODS: Data came from the Understanding America Study, a nationally representative panel of U.S. adults (N=8,397; March 10, 2020-March 29, 2021). A growth mixture model was deployed to identify subgroups with similar regular cannabis use. Sociodemographic correlates of subgroups were examined using multinomial logistic regression. RESULTS: Four cannabis-use groups were identified. Most participants did not regularly use cannabis (no regular use; 81.7%). The other groups increased regular use until April 2020 but then diverged. Some (7.1%) decreased thereafter, whereas others (3.4%) maintained their elevated use until October 26, 2020 before decreasing. The last group (7.7%) sustained their elevated use throughout. Individuals aged between 18 and 39 years, unmarried, living in poverty, without a college degree, and with longer unemployment or underemployment spells had higher odds of being in the other groups with more weekly use than in the no-regular-use group. CONCLUSIONS: The analyses revealed population subgroups with prolonged regular cannabis use and a disproportionate concentration of socioeconomically vulnerable members of society in these subgroups. These findings elucidate important heterogeneity in the subpopulations using cannabis, highlighting the urgent need to tailor public health programs for subgroups that may have unique service needs.

Intraoperative pancreatoscopy in pancreaticoduodenectomy for intraductal papillary mucinous neoplasms of the pancreas: Application to the laparoscopic approach.

BACKGROUND: /Purpose: Owing to the characteristics of IPMNs, which have variable skipped lesions along the main pancreatic duct (MPD), determining the surgical margins is very difficult. This study aimed to investigate the efficacy and potential oncologic impact of intraoperative pancreatoscopy (IOP) compared to frozen section biopsy (FSB) in pancreaticoduodenectomy (PD) for pancreatic head IPMNs. METHODS: Data of patients who underwent PD for IPMNs of the pancreas between October 2007 and May 2020 were retrospectively reviewed. IOP was performed in selected patients with IPMNs with inconclusive MPD involvement based on preoperative evaluations. Patients were divided into two groups, IOP group, FSB group. Clinicopathologic features and oncologic outcomes were compared between two groups. RESULTS: 60 patients underwent PD (laparoscopic or robotic, 42; open, 18) for pancreatic head IPMNs. IOP was safely performed in 28 patients, including minimally invasive approach used in 21 patients (35%). IOP group had a significantly larger MPD size (9.15 ± 4.79 mm vs 6.43 ± 4.11 mm, p = 0.021). Based on IOP, the initial surgical plan could be changed in 5 patients (17.8%) for complete resection. Recurrence occurred in 2 patients in FSB group and 3 patients in IOP group during the follow-up period (33.2 months, [range, 3.5-131.4 months]). Overall disease-free survival rate did not significantly differ between two groups (p = 0.529). CONCLUSIONS: IOP can be safely performed in patients with pancreatic head IPMNs with MPD dilatation, even in the laparoscopic approach. Further studies evaluating the long-term oncologic effect of IOP for the management of IPMNs are required.

Developmental inflection point for the effect of maternal childhood adversity on children's mental health from childhood to adolescence: Time-varying effect of gender differences.

Childhood adversities have a well-established dose-response relationship with later mental health. However, less attention has been given to intergenerational influences. Further, it is unknown how intergenerational influences intersect with children's developmental stages and gender. The current study examined whether a developmental inflection point exists when the intergenerational influences of childhood adversities gain salience and explored differences by children's gender. Data were from the Young Women and Child Development Study (n = 361). Time-varying effect models (TVEMs) and moderation TVEMs by child's gender were evaluated. Our findings reveal that ages 5-8, the period of transition into primary schools, may represent a developmental inflection point when the intergenerational influences of maternal childhood adversity start emerging substantially. The results from gender interaction TVEMs reveal that maternal childhood adversity was a statistically significant predictor of internalizing problems until age 11, regardless of child's gender, and remained statistically significant for girls' internalizing problems until age 16.7. For externalizing problems, maternal childhood adversity was a statistically significant predictor until age 13, regardless of gender.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Short and long-term outcomes of minimally invasive central pancreatectomy: Comparison with minimally invasive spleen-preserving subtotal distal pancreatectomy.

BACKGROUND: Central pancreatectomy(CP) is more complex surgery and higher complication rate than distal pancreatectomy(DP). However, with the development of minimally invasive surgery, CP has become a safer surgery technique. In this study, we compare minimally invasive CP(MI-CP) and Minimally invasive spleen-preserving subtotal DP(MI-SpSTDP) to figure out the short-term and long-term outcomes of MI-CP. METHODS: From March 2007 to June 2020, 36 cases of MI-SpSTDP and 23 cases of MI-CP were performed for benign and borderline malignant pancreatic tumors in Severance hospital. The occurrence of postoperative pancreatic fistula(POPF) and Clavian-Dindo classification grade 3 or more in the two group was investigated, and the Controlling nutritional status scores(CONUT score) before and 1-year after surgery were compared to determine the long-term outcomes of exocrine function. RESULTS: There was no difference in postoperative complications including POPF between the two groups(17.4% vs 5.1%, p = 0.294). And there were no statistical differences in either the MI-CP group (0.74 ± 0.75 vs. 0.78 ± 0.99, p = 0.803) or the MI-SpSTDP group (0.86 ± 0.83 to 0.61 ± 0.59, p = 0.071). CONCLUSIONS: MI-CP had longer operation time and hospital stay and is safe and effective in preserving endocrine and exocrine functions in treatment of benign or borderline tumors located at the neck or proximal body of the pancreas.

Validation of original, alternative, and updated alternative fistula risk scores after open and minimally invasive pancreatoduodenectomy in an Asian patient cohort.

BACKGROUND: This study aimed to validate and compare the performance of the original fistula risk scores (o-FRS), alternative (a-FRS), and updated alternative FRS (ua-FRS) after open pancreatoduodenectomy (OPD) and laparoscopic pancreatoduodenectomy (LPD) in an Asian patient cohort. METHODS: Data of 597 consecutive patients who underwent PD (305 OPD, 274 LPD) were collected from two tertiary centers. Model performance was assessed using the area under the receiver operating curve (AUC). RESULTS: The overall AUC values of o-FRS, a-FRS, and ua-FRS were 0.67, 0.69, and 0.68, respectively, which were lower than those of the Western validation. Three FRS systems had similar AUC values in the overall and OPD groups, whereas ua-FRS had a higher AUC than o-FRS in the LPD group. The accuracy of ua-FRS (47.2%) was higher than that of o-FRS (39.0%) and a-FRS (19.5%) overall, but low specificity and low positive predictive value were observed regardless of the operative type across the three FRS systems. In the multivariate analysis, pathology, estimated blood loss, and body mass index were not independent risk factors for CR-POPF in the OPD and LPD groups. CONCLUSIONS: Current FRS systems have some limitations, including a relatively lower performance in an Asian cohort, low positive predictive values, and inclusion of insignificant risk factors.

Serum kisspeptin levels mainly depend on ovarian expression of Kiss1 mRNA in female rats.

The hypothalamic kisspeptin/KISS1 receptor system is essential for puberty onset and reproductive development. Although serum kisspeptin might be associated with puberty, its levels, according to developmental stage, and its origin still remain unclear. This study evaluated the changes in serum kisspeptin levels during puberty and the corresponding Kiss1 mRNA and protein expression in various organs of female rats to identify the source of serum kisspeptin. Tissues from several organs, including the ovaries and anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) in the hypothalamus, were obtained for assessing Kiss1 mRNA and protein expressions. Serum kisspeptin levels progressively increased with developmental stages until the peripubertal stage. The ovaries showed the highest Kiss1 expression among the organs examined. Next, we explored the changes in serum kisspeptin levels and hypothalamic Kiss1 expression in ovariectomized and estradiol-treated ovariectomized rats. Serum kisspeptin levels decreased regardless of estradiol treatment; Kiss1 expression was enhanced by ovariectomy and estradiol treatment in the ARC, while it was decreased by ovariectomy and enhanced by estradiol in the AVPV, suggesting that serum kisspeptin may be associated with pubertal development and mainly depended on ovarian Kiss1 expression. Thus, serum kisspeptin levels are associated with puberty and may serve as a downstream marker of ovarian reproductive function.

Should the Splenic Vein Be Preserved-Fate of Sinistral Portal Hypertension after Pancreatoduodenectomy with Vascular Re-Section for Pancreatic Cancer.

Background: This study aims to evaluate sinistral portal hypertension (SPH) development and its clinical impact on the long-term outcomes of patients with pancreatic cancer who underwent surgical resection with splenic vein (SV) ligation. Methods: Data from 94 consecutive patients who underwent pancreatoduodenectomy (PD) with vascular resection for pancreatic cancer from 2008 to 2019 were retrospectively collected. The patients were divided into two groups according to whether the SV was preserved or ligated during the surgery. Their computed tomography images were serially reviewed (preoperative, 6-, 12-, and 24-months postoperative) with clinical parameters. The degree of variceal formation (variceal score) and splenomegaly were assessed, and the oncologic outcomes were compared between the two groups. Variceal score in the SV ligation group was significantly higher than that in the SV saving group at the same postoperative periods (SV saving vs. ligation: 12 months, 0.9 ± 1.3 vs. 3.5 ± 2.2, p < 0.001; 24 months, 1.4 ± 1.8 vs. 4.0 ± 3.4, p = 0.009). Clinically relevant variceal bleeding was noted in one patient from the SV ligation group (SV saving vs. ligation: 0.0% vs. 3.1%, p = 0.953). In survival analysis, there was no significant difference between the two groups (DFS; SV saving vs. ligation: 13.0 (11.1−14.9) months vs. 13.0 (10.4−15.6) months, p = 0.969, OS; SV saving vs. ligation: 35.0 (19.9−50.1) months vs. 27.0 (11.6−42.4) months, p = 0.417). Although SV ligation induced SPH during PD for pancreatic cancer, it did not lead to clinically significant long-term complications. In addition, it did not impact the long-term survival of patients with resected pancreatic head cancer.

Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy.

BACKGROUND: The Systemic Inflammation Response Index (SIRI) has been used to predict the prognosis of various cancers. This study examined SIRI as a prognostic factor in the neoadjuvant setting and determined whether it changing after chemotherapy is related to patient prognosis. METHODS: Patients who underwent pancreatic surgery following neoadjuvant chemotherapy for pancreatic cancer were retrospectively analyzed. To establish the cut-off values, SIRIpre-neoadjuvant, SIRIpost-neoadjuvant, and SIRIquotient (SIRIpost-neoadjuvant/SIRIpre-neoadjuvant) were calculated and significant SIRI values were statistically determined to examine their effects on survival rate. RESULTS: The study included 160 patients. Values of SIRIpost-neoadjuvant ≥ 0.8710 and SIRIquotient <0.9516 affected prognosis (hazard ratio [HR], 1.948; 95% confidence interval [CI], 1.210-3.135; ∗∗P = 0.006; HR, 1.548; 95% CI, 1.041-2.302; ∗∗P = 0.031). Disease-free survival differed significantly at values of SIRIpost-neoadjuvant < 0.8710 and SIRIpost-neoadjuvant ≥ 0.8710 (P = 0.0303). Overall survival differed significantly between SIRIquotient <0.9516 and SIRIquotient ≥0.9516 (P = 0.0368). CONCLUSIONS: SIRI can predict the survival of patients with pancreatic ductal adenocarcinoma after resection and neoadjuvant chemotherapy. Preoperative SIRI value was correlated with disease-free survival, while changes in SIRI values were correlated with overall survival.

Laparoscopic distal pancreatosplenectomy for left-sided pancreatic cancer in patients with radical subtotal gastrectomy for gastric cancer.

After radical subtotal gastrectomy (RSTG) for stomach cancer, the remnant stomach is supposed to be perfused through the short gastric vessels. What if a patient who received previous RSTG is diagnosed with resectable distal pancreatic cancer? Can radical distal pancreatosplenectomy (DPS) be performed safely without ischemic damage to the remnant stomach? Unfortunately, there are limited studies on this specific clinical issue. Notably, in spite of rare clinical presentation, it is expected to increase due to prolonged survival of patients with resected gastric cancer. Therefore, we aimed to demonstrate the safety and feasibility of the radical DPS in patients with previous RSTG. In this study, we investigated perioperative and long-term survival outcomes of DPS for left-sided pancreatic cancer in patients with previous RSTG.

Neoadjuvant FOLFIRINOX Followed by Pancreatoduodenectomy for Pancreatic Cancer in Patients with Previous Transhiatal Esophagectomy for Esophageal Cancer.

During pancreaticoduodenectomy after transhiatal esophagectomy, the preservation of the blood supply to the gastric conduit is technically difficult due to adhesion. Here, we present a case of successful pancreaticoduodenectomy after neoadjuvant chemotherapy in a patient with pancreatic head cancer who previously underwent subtotal esophagectomy with gastric reconstruction for esophageal cancer. A 69-year-old man who had undergone cholecystectomy 20 years prior and transhiatal esophagectomy 6 years prior for esophageal cancer presented to our hospital for indigestion. Computed tomography and magnetic resonance imaging revealed a 2.8-cm pancreatic head cancer, with focal abutment with the gastroduodenal artery, right gastroepiploic artery, and right colic vein. After discussion with the multidisciplinary team, the patient underwent neoadjuvant chemotherapy with six cycles of FOFIRINOX. The patient successfully underwent pancreatectomy, which preserved the pylorus. We preserved the gap between the gastric tube and the left lateral segment of the liver to avoid injuring the right gastric artery and vein. The tumor was found to be invading the gastroduodenal artery; thus, we performed R0 resection of the gastroduodenal artery and an end-to-end anastomosis between the gastroduodenal artery and the right gastroepiploic artery. After completing the surgical procedure, we added Braun anastomosis to reduce the incidence of delayed gastric emptying. Pancreaticoduodenectomy after transhiatal esophagectomy can be performed with preservation of the blood supply to the neogastric tube by reconstructing the major vessels, even in cases in which the tumor is invading or abutting the major vessels.

Total laparoscopic versus robotic-assisted laparoscopic pancreaticoduodenectomy: which one is better?

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a challenging procedure. Laparoscopic pancreaticoduodenectomy (LPD) is feasible and safe. Since the development of robotic platforms, the number of reports on robot-assisted pancreatic surgery has increased. We compared the technical feasibility and safety between LPD and robot-assisted LPD (RALPD). METHODS: From September 2012 to August 2020, 257 patients who underwent MIPD for periampullary tumors were enrolled. Of these, 207 underwent LPD and 50 underwent RALPD. We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographics and surgical outcomes. RESULTS: After PSM analysis, no difference was noted in demographics. Operation times and estimated blood loss were similar, as was the incidence of complications (p > 0.05). In subgroup analysis in patients with soft pancreas with pancreatic duct ≤ 2 mm, no significant between-group difference was noted regarding short-term surgical outcomes, including clinically relevant POPF (CR-POPF) (p > 0.05). In multivariable analysis, the only soft pancreatic texture was a predictive factor (HR 3.887, 95% confidence interval 1.121-13.480, p = 0.032). CONCLUSION: RALPD and LPD are safe and effective for MIPD and can compensate each other to achieve the goal of minimally invasive surgery.

A Prognostic Impact of Splenectomy in Laparoscopic Distal Pancreatectomy on Benign/Borderline Pancreatic Tumors: A Change of the Era.

PURPOSE: In the past, spleen preservation during distal pancreatectomy (DP) was preferred; however, more recent studies reported comparable results between splenectomy and spleen preserving. We retrospectively reviewed patients in a single center who underwent laparoscopic DP with/without splenectomy, and evaluated the chronologic changes of surgical outcomes of the two procedures. MATERIALS AND METHODS: Patients who underwent laparoscopic DP with or without splenectomy due to benign/borderline tumor from 2005 to 2019 were included in this study. We divided this period into Era 1 (2005-2012) and Era 2 (2013-2019), and compared the chronological evolution of surgical outcomes of laparoscopic distal pancreatosplenectomy (LDPS) to those of laparoscopic spleen-preserving distal pancreatectomy (LSpDP), including the long-term postoperative immunologic profiles. RESULTS: A total of 198 cases were included (LSpDP: 80 cases; LDPS: 118 cases). As the period changed from Era 1 to Era 2, the ratio of LSpDP decreased and the surgical outcomes of LDPS improved. In Era 1, LSpDP group showed superior results compared to LDPS group in terms of hospital days and postoperative pancreatic fistula ratio; however, in Era 2, the surgical outcomes showed no statistical differences. No significant differences were observed in all of the immunologic markers. CONCLUSION: We carefully conclude that during laparoscopic DP, combined splenectomy can be equivalent to spleen preserving in surgical and immunological outcomes, and inevitable splenectomy can be safely conducted.

Cumulative Neighborhood Risk and Subsequent Internalizing Behavior among Asian American Adolescents.

Neighborhood disadvantage is a developmental context that may contribute to Asian American adolescent internalizing problems, yet there is a dearth of longitudinal studies as well as examination of cultural protective factors. Co-ethnic density, or the proportion of individuals of the same racial/ethnic background in the neighborhood that is often cited as a protective factor for racial/ethnic minority groups, has not been adequately examined in Asian American youth. This study examined the longitudinal association between cumulative neighborhood risk and internalizing behavior, and the moderating role of sex and co-ethnic density using an Asian American subsample (N = 177; 45.2% female; ages 10-12, 14-15; Cambodian, Chinese, Filipino, Hmong, Japanese, Korean, Laotian, Samoan, Vietnamese, and other ethnic backgrounds) of a longitudinal panel study over a span of 6 years. Cumulative neighborhood risk during early adolescence (ages 10-14) was significantly associated with internalizing behavior at mid-adolescence (age 15) controlling for prior levels of internalizing behavior. There was no evidence of moderation by co-ethnic density or sex, indicating that reducing neighborhood disadvantage may be a promising preventive measure to address mental health problems for both sexes of Asian American adolescents.

Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16-80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80-10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29-8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48-12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01-27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.