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.

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.

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.

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.

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.