Harnessing Dual-Fluorescence Lifetime Probes to Validate Regulatory Mechanisms of Organelle Interactions.

Organelles are dynamic yet highly organized to preserve cellular homeostasis. However, the absence of time-resolved molecular tools for simultaneous dual-signal imaging of two organelles has prevented scientists from elucidating organelle interaction regulatory mechanisms on a nanosecond timescale. To date, the regulatory mechanisms governing the interaction between endoplasmic reticulum (ER) and autophagosomes are unknown. In this study, we propose a strategy for developing dual-fluorescence lifetime probes localized to the endoplasmic reticulum and autophagosomes to investigate their interaction regulatory mechanisms. Using the robust probe CF2, we investigated the regulatory mechanisms between ER and autophagosomes and discovered the following: (i) motile autophagosome in ER tips drives the ER tubule to grow and slide; (ii) the ER reticulate tubule forms a three-way junction centered on the autophagosome; (iii) ER autophagy is a type of cell damage index during drug-induced apoptosis. Thus, this study advances our knowledge of organelle interaction regulatory mechanisms, shedding light on the identification of therapeutic targets for neurodegenerative diseases.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Revisiting Fluorescent Calixarenes: From Molecular Sensors to Smart Materials.

Calix[n]arenes (n = 4, 5, 6, 8) are "chalicelike" phenol-based macrocycles that are among the most fascinating and highly studied scaffolds in supramolecular chemistry. This stems from the functional and tunable diversity at both their upper and lower rims, their preorganized nonpolar cavities and preorganized ion-binding sites, and their well-defined conformations. Conjugation of calixarene scaffolds with various fluorogenic groups has led to the development of smart fluorescent probes that have been utilized as molecular sensors, in bioimaging, for drug and gene delivery, in self-assembly/aggregation, and as smart materials. The fine-tuning and incorporation of different ligating sites in the calix[4]arene scaffold have produced numerous molecular sensors for cations, anions, and biomolecules. Moreover, the aqueous solubility of p-sulfonatocalix[4]arenes has engendered their potential use in drug/gene delivery and enzymatic assays. In addition, because of their strong optical properties, fluorescent calix[4]arenes have been used to develop smart materials, including gels as well as nonlinear optical, organic light-emitting diode, and multiphoton materials. Finally, significant developments in the utility of fluorescent higher calixarenes have been made for bioapplications. This review critically summarizes the recent advances made in all of these different areas.

Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy.

BACKGROUND: Robotic surgery is a novel approach that scores over conventional minimally invasive approaches, even in pancreatic surgery. We investigated clinical outcomes of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy (RA-MIPD). METHODS: Total 150 patients who underwent RA-MIPD between 2015 and 2018 were compared with 710 patients who underwent open pancreatoduodenectomy (PD) during the same period. Demographics and surgical outcomes were analyzed, and propensity score-matched (PSM) analysis was performed to evaluate complications including clinically relevant postoperative pancreatic fistula (CR-POPF) and oncologic outcomes in patients with malignancy. RESULTS: PSM analysis was performed based on the pancreatic fistula risk. Patients undergoing RA-MIPD were younger (RA-MIPD vs. open PD: 61.2 vs. 65.5 years, P < 0.001); however, no significant intergroup difference was observed in sex (P = 0.091) and body mass index (P = 0.281). Operation time was longer in the RA-MIPD group (361.2 vs. 305.7 min, P < 0.001); however, estimated blood loss did not significantly differ (515.6 vs. 478.0 mL, P = 0.318). Overall complication (24.7% vs. 30.9%, P = 0.178) and CR-POPF rates (6.7% vs. 6.9%, P > 0.999) were similar. The RA-MIPD group showed lower pain scores and shorter length of postoperative hospitalization (11.5 vs. 17.2 days, P < 0.001). After PSM analysis for cancer and staging among patients with malignancies, no significant intergroup difference was observed in the R0 resection rate (96.7% vs. 93.3%, P = 0.527), tumor size (2.59 vs. 2.60 cm, P = 0.954), total number of retrieved lymph nodes (17.0 vs. 16.6, P = 0.793), and 2-year survival rates (84.4% vs. 77.8%, P = 0.898). CONCLUSIONS: Compared with open PD, RA-MIPD is associated with better or at least similar early perioperative and equivalent midterm survival outcomes. RA-MIPD is safe and feasible and enables early postoperative recovery. RA-MIPD is expected to play a key role in near future.

Progression of Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasm Associates With Cyst Size.

BACKGROUNDS & AIMS: Most guidelines for management of patients with intraductal papillary mucinous neoplasms (IPMN) vary in proposed surveillance intervals and durations-these are usually determined based on expert opinions rather than substantial evidence. The progression of and optimal surveillance intervals for branch-duct IPMNs (BD-IPMN) has not been widely studied. We evaluated the progression of BD-IPMN under surveillance at a single center, and determined optimal follow-up intervals and duration. METHODS: We performed a retrospective analysis of 1369 patients with BD-IPMN seen at Seoul National University Hospital in Korea from January 2001 through December 2016. We included only patients whose imaging studies showed classical features of BD-IPMN, and collected data from each patient over time periods of at least 3 years. We reviewed radiologic and pathologic findings, and performed linear and binary logistic regressions to estimate cyst growth. RESULTS: The median annual growth rate of the cyst was 0.8 mm over a median follow-up time of 61 months. During surveillance, 46 patients (3.4%) underwent surgery because of disease progression after a median follow-up time (in this group) of 62 months. Worrisome features were observed in 209 patients (15.3%) during surveillance, including cyst size of 3 cm or more (n = 109, 8.0%), cyst wall thickening (n = 51, 3.7%), main pancreatic duct dilatation (n = 77, 5.6%), and mural nodule (n = 43, 3.1%). Along with annual rate of cyst growth, incidences of main pancreatic duct dilatation and mural nodules associated with the sizes of cysts at detection (P < .001). CONCLUSIONS: In a retrospective analysis of patients with BD-IPMN followed for more than 5 years, we found most cysts to be indolent, but some rapidly grew and progressed. Surveillance protocols should therefore be individualized based on initial cyst size and rate of growth.

In Vivo Imaging of Endogenously Produced HClO in Zebrafish and Mice Using a Bright, Photostable Ratiometric Fluorescent Probe.

A high brightness red fluorescent probe (S-BODIPY) has been developed for the sensitive and specific imaging of HClO/ClO- in vitro and in vivo. This probe exhibits some distinctive features such as excellent resistance to photobleaching, a high fluorescence brightness, high selectivity, as well as a good biocompatibility. Upon oxidation of the thio-ether group into sulfoxide, the probe showed a noticeable ratiometric fluorescence response toward ClO- with fast response (within 30 s) and a low detection limit (59 nM). The probe demonstrated the successful imaging of exogenous and endogenous HClO/ClO- in living HeLa cells, zebrafish, and mice with high signal-to-noise ratios. S-BODIPY allows for the real-time monitoring the level of ClO- in living cells by ratiometric fluorescence imaging, opening up exciting prospects to develop red and even near-infrared BODIPYs with high brightness and good photostability for in vivo imaging.

Shedding light on tau protein aggregation: the progress in developing highly selective fluorophores.

Historically, in Alzheimer's disease research, a lot of attention has been paid to the development of highly selective fluorophores for beta amyloid plaques. With a shift in the understanding of the disease and the importance of a network of cross-talk interactions, the development of small-molecule fluorescent dyes with high selectivity for (hyperphosphorylated) tau protein aggregates in neurofibrillary tangles has been gaining increasing attention. Fluorescent dyes for the selective labelling of tau aggregates in histological AD brain sections have been described, spanning the entire visible range of the electromagnetic spectrum. Despite the relatively early stages of the development of the field, a large diversity in probe architectures has been reported. Importantly, a handful of near-infrared-emissive dyes have been described as well, and some of these have exhibited good pharmacological profiles, with a significant blood-brain-barrier permeability, and a demonstrated ability to label tau tangles in vivo in small-animal models of Alzheimer's disease and other tauopathies. The developments summarized in the current work are expected to aid the unravelling of the diverse set of players in the etiology of Alzheimer's disease. In this tutorial review, we seek to provide the reader with an overview of the most important recent developments and hope to provide some guidelines for the design of future probes.

Survival Comparison of Different Operation Types for Middle Bile Duct Cancer: Bile Duct Resection versus Pancreaticoduodenectomy Considering Complications and Adjuvant Treatment Effects.

BACKGROUND: Margin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy (PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer. MATERIALS AND METHODS: From 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin. RESULTS: The 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (p = 0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (p < 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (p = 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (p = 0.003). CONCLUSION: The survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes.

Role of neoadjuvant treatment in resectable pancreatic cancer according to vessel invasion and increase of CA19-9 levels.

BACKGROUND/PURPOSE: The efficacy of neoadjuvant treatment (NAT) for resectable pancreatic cancer remains debatable, particularly in patients with portal vein (PV)/superior mesenteric vein (SMV) contact and elevated serum carbohydrate antigen (CA) 19-9. This study investigated the clinical significance of PV/SMV contact and CA19-9 levels, and the role of NAT in resectable pancreatic cancer. METHODS: A total of 775 patients who underwent surgery for resectable pancreatic cancer between 2007 and 2018 were included. Propensity score-matched (PSM) analysis (1:3) was performed based on tumor size, lymph node enlargement, and PV/SMV contact. Subgroup analyses were performed according to PV/SMV contact and CA19-9 level. RESULTS: Among the patients, 52 underwent NAT and 723 underwent upfront surgery. After PSM, NAT group showed better survival than upfront surgery group (median 30.0 vs 22.0 months, P = .047). In patients with PV/SMV contact, NAT tended to have better survival (30.0 vs 22.0 months, P = .069). CA19-9 >150 U/mL was a poor prognostic factor, with NAT showing a significant survival difference compared with upfront surgery (34.0 vs 18.0 months, P = .004). CONCLUSIONS: Neoadjuvant treatment showed better survival than upfront surgery in resectable pancreatic cancer. In patients with PV/SMV contact or CA19-9 >150 U/mL, NAT showed a survival difference compared to upfront surgery; therefore, NAT could be considered in these patients.

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.

Sub 50 nm nano-patterns with carbon based spin-on organic hardmask.

Carbon based spin-on organic hardmask (C-SOH) was used as an imprint resin to fabricate sub 50 nm sized patterns. Imprinting of C-SOH was done with a polyurethaneacrylate (PUA) stamp. Patternability and etch resistance of the C-SOH resin was compared to poly(methyl methacrylate) (PMMA). C-SOH can be patterned at the nanosize using imprint lithography and exhibits superior etch resistance, especially for F-based plasmas. Due to the poor etch resistance of imprint resin such as PMMA, it is seldom used as an etch mask to form nano-structures by etching the Si3N4 layer. However, such a nano-structure was able to be formed by etching the Si3N4 layer using C-SOH as an etch mask.

Fabrication of a polyurethane acrylate/polyimide-based polymer mold for a hot embossing process.

A high-thermal-resistance polymer-based flexible imprint mold was developed to be used in a hot embossing process. This mold was readily replicated in a UV curing imprint process and can be used as a mold for hot embossing and thermally curing imprint processes. The nano-sized pattern of this mold was not degraded by soaking at 350 degrees C for 10 min and the pattern fidelity was maintained after 10 separate cyclic heating tests between 0 degrees C and 350 degrees C. The substrate of this flexible mold was PI film, and a UV-cured polyurethane acrylate (PUA) layer was used to form the nano-scale patterns. The durability of this polymeric mold was tested by repetitive hot embossing processes. Nano-scale patterns of the mold were readily transferred to a PMMA layer coated onto a Si substrate by hot embossing lithography at 180 degrees C. After 10 cycles of hot embossing processes, no damage or degradation was observed in the flexible polymer mold. Using this polymer mold, patterns as small as 50 nm were successfully transferred to a Si substrate. Due to the flexibility of the polymer mold, nano-scale patterns were successfully transferred to a non-flat acryl substrate by hot embossing lithography.

Management Algorithms for Pancreatic Cystic Neoplasms.

CONTEXT.­: The detection of pancreatic cystic neoplasms (PCNs) has increased owing to the advancement and widespread use of imaging modalities, resulting in differences between past and current management methods for PCNs, including intraductal papillary mucinous neoplasms (IPMNs). Therefore, clinicians should accurately diagnose and determine appropriate treatment strategies. However, previously published treatment guidelines for IPMNs present different indications for treatment. OBJECTIVE.­: To review the current status of PCNs, including epidemiologic change, malignancy risk, and factors for treatment, and to provide the optimal management algorithms for PCNs, including IPMNs, from the clinician's point of view. DATA SOURCES.­: Literature review of published studies and the authors' own work. CONCLUSIONS.­: The treatment of PCNs relies on the type of cyst that is present or suspected. Serous cystic neoplasms are usually benign, and observation is sufficient. However, surgical treatment is required for mucinous cystic neoplasms, and malignancy risk differs according to lesion size. Solid pseudopapillary neoplasms also require surgery. The detection of small IPMNs has been increasing, and most branch duct-type IPMNs are dormant. However, cysts 3 cm or larger or growing branch duct-type IPMNs must be carefully monitored because of the increasing risk of malignancy. Therefore, surveillance strategies should be different according to the size of the lesions. A tailored approach is needed for selecting surgery or surveillance, considering the malignancy potential of the lesion and patient-associated factors such as operative risks and life expectancy. Nomograms are valuable tools for selecting treatment methods as a customized approach for IPMNs.

Long-Term Oncologic Outcomes for T2 Gallbladder Cancer According to the Type of Surgery Performed and the Optimal Timing for Sequential Extended Cholecystectomy.

BACKGROUND: Sequential extended cholecystectomy (SEC) is currently recommended for T2 and higher gallbladder cancer (GBC) diagnosed after simple cholecystectomy (SC), but the value and timing of re-resection has not been fully studied. We evaluated the long-term oncologic outcomes of T2 GBC according to the type of surgery performed and investigated the optimal timing for SEC. METHODS: Patients diagnosed with T2 GBC who underwent SC, extended cholecystectomy (EC), or SEC between 2002 and 2017 were retrospectively reviewed. Those who underwent other surgical procedures or those with incomplete medical records were excluded. Overall survival (OS) and disease-free survival (DFS) according to the types of surgeries and prognostic factors for OS and DFS were analyzed. Survival analysis was done between groups that were divided according to the optimal cutoff time interval between SC and SEC based on DFS data. RESULTS: Of the 226 T2 GBC patients, 53, 173, and 44 underwent SC, EC, and SEC, respectively. The 5-year OS rate was 50.1%, 73.2%, and 78.7%, and the DFS rate was 46.8%, 66.3%, and 65.2% in the SC, EC, and SEC groups, respectively. EC (p = 0.001 and p = 0.001) and SEC (p = 0.007 and p = 0.065) groups had better 5-year OS and DFS rates than the SC group. Preoperative CA 19-9 level > 37 U/mL (HR 1.56; 95% CI 1.87-2.79; p < 0.001) and N1 stage (HR 2.88; 95% CI 1.76-4.71; p < 0.001) were associated with poorer prognosis. The optimal cutoff interval between SC and SEC was 28 days. Patients who underwent SEC ≤ 28 days after the initial cholecystectomy had better 5-year DFS rates than patients who underwent SEC after > 28 days (75.0% vs. 52.8%, p = 0.023). CONCLUSIONS: SEC is recommended for T2 GBC diagnosed after SC, because SEC provides better survival outcomes than SC alone. A time interval of less than 28 days to SEC is associated with an improved DFS.

Stool Elastase as an Independent Prognostic Factor in Patients with Pancreatic Head Cancer.

(1) Background: Patients with pancreatic exocrine insufficiency (PEI) have an increased risk of malnutrition, which in turn increases morbidity and mortality and is frequent in pancreatic head cancer. This study aimed to analyze the utility of PEI measured using the stool elastase (SE) level to predict the prognosis of patients with pancreatic head cancer. (2) Methods: Patients who underwent pancreaticoduodenectomy for pancreatic cancer at our institution between 2011 and 2015 were included. Only patients with data on preoperative SE levels were analyzed. Patients were classified into low and high SE groups based on preoperative SE levels (low < 100 µg/g < high). (3) Results: The median preoperative SE level was 67.2 µg/g, and 84 of 143 (58.7%) patients were included in the low SE group. The two groups had significantly different overall survival (OS) and disease-free survival (DFS), and the low SE group had a worse prognosis. In multivariate analysis, SE level < 100 µg/g and lymph node metastasis were independent poor prognostic factors for OS and DFS. (4) Discussion: PEI measured using SE levels is an independent prognostic factor in patients with pancreatic head cancer undergoing pancreaticoduodenectomy. Since poor nutritional status may be related to prognosis in patients with low levels of stool elastase preoperatively, aggressive treatment may be required.

ROBOT-assisted pancreatoduodenectomy in 300 consecutive cases: Annual trend analysis and propensity score-matched comparison of perioperative and long-term oncologic outcomes with the open method.

BACKGROUND/PURPOSE: We previously reported perioperative and oncologic outcomes of robot-assisted pancreatoduodenectomy (RAPD); however, the follow-up period in RAPD was relatively short, and disease-matched survival analyses were lacking. Therefore, this study investigated time trends of perioperative and long-term disease-matched outcomes of RAPD. METHODS: Annual clinicopathologic outcomes of 328 patients with RAPD between 2015 and 2020 were analyzed and compared with 929 patients with open PD using the propensity score-matched (PSM) analysis based on postoperative pancreatic fistula (POPF) risk and oncologic variables in malignant patients. RESULTS: Robot-assisted pancreatoduodenectomy cases increased from 10 (6.3%) in 2015 to 116 (50.2% of total PD) in 2020, with malignancy proportion increasing from 50.0% to 80.2%. POPF risk-based PSM analysis showed that compared with open PD, RAPD had younger patients (63.7 vs 65.6 years, P = .018), longer operation time (339.1 vs 290.0 min, P < .001); however, estimated blood loss (P = .275), complications (17.1% vs 18.3%, P = .702), and clinically relevant POPF (9.8% vs 11.1%, P = .584) were similar with shorter postoperative hospital stay (10.8 vs 15.6 days, P < .001). In disease and stage-matched malignant patients, R0 resection (93.9% vs 91.2%, P = .376), total retrieved lymph node (18.2 vs 19.9, P = .058), and 5-year survival rate (57.3% vs 60.6%, P = .406) were similar between RAPD and open PD, also in pancreatic cancer patients (31.6% vs 26.3%, P = .068). CONCLUSIONS: Robot-assisted pancreatoduodenectomy demonstrated similar perioperative outcomes with earlier recovery and equivalent long-term survival with open PD. RAPD is safe and feasible for periampullary lesions, including pancreatic cancers, and its role will expand in the era of minimally invasive surgery.

The incidence and clinical features of familial pancreatic cancer in Korea.

BACKGROUND: A history of familial pancreatic cancer (FPC) increases the incidence of pancreatic cancer (PC) among first-degree relatives. We aimed to determine the incidence of FPC and analyze its clinical characteristics. METHODS: Between 2010 and 2014, 1159 patients with PC were included in the study. We evaluated the incidence of FPC, clinicopathological features, and survival prognosis between FPC and non-FPC patients. We further analyzed the clinical outcomes of 389 patients with PC who underwent curative-intent surgery. RESULTS: Familial pancreatic cancer incidence was 3.1% (n = 36) among all patients with PC (n = 1159). FPC was diagnosed at an advanced clinical stage compared to non-FPC (P = .041). The tested variables and 5-year survival rate (5YSR) between FPC and non-FPC after propensity score matching had no differences (5YSR: 4.6% vs 2.6%, P = .834). Among PC patients who underwent curative-intent surgery (n = 389), FPC incidence was 1.8% (n = 7). FPC patients were older than non-FPC patients (75.3 ± 4.7 years vs 64.0 ± 9.9 years, P < .001). 5YSR tended to differ between FPC and non-FPC (14.3% vs 22.5%, P = .07) groups. CONCLUSION: Familial pancreatic cancer is diagnosed at an advanced stage, and FPC that has undergone resection is associated with older age or worse prognosis. A prospective nationwide pedigree registration system was required.

Can Surgical Resection of Metastatic Lesions Be Beneficial to Pancreatic Ductal Adenocarcinoma Patients with Isolated Lung Metastasis?

In the era of effective chemotherapy on pancreatic ductal adenocarcinoma (PDAC) with distant metastasis, data on the effects of metastatectomy are lacking. So, we investigated the effect of metastatectomy on survival after metastasis in PDAC patients with isolated lung metastasis. This retrospective study analyzed 1342 patients who were histologically diagnosed with PDAC with distant metastasis from January 2007 to December 2018, of which 83 patients had isolated pulmonary metastasis. Additionally, 4263 patients were extracted from the National Cancer Database (NCDB) and analyzed. Log-rank test and Kaplan−Meier survival analysis were used to analyze survival after metastasis. The five-year survival rate was significantly higher in patients who underwent pulmonary metastatectomy than in those who received only chemotherapy or supportive treatment (60.6% vs. 6.2% vs. 0.0%, p < 0.001). A similar trend was observed in the NCDB (two-year survival rate, 27.4% vs. 15.8% vs. 4.7%, p < 0.001). In the multivariate analysis, lung lesion multiplicity (hazard ratio (HR) = 2.004, p = 0.017), metastatectomy (HR = 0.278, p = 0.036), chemotherapy (HR = 0.434, p = 0.024), and chemotherapy cycles (HR = 0.300, p < 0.001) had significant effects on survival. Metastatectomy with primary pancreatic lesions is recommended with effective chemotherapy in PDAC patients with isolated lung metastasis.

The development and clinical efficacy of simulation training of open duct-to-mucosa pancreaticojejunostomy using pancreas and intestine silicone models.

Purpose: As pancreaticojejunostomy (PJ) is a challenging anastomosis, an education program is needed to train young surgeons to perform PJ. This study evaluated the effects of simulation-based training of open PJ using pancreas and intestine silicone models. Methods: Five videos pancreatobiliary clinical fellows who did not perform PJ participated in this study. After watching the master video created by a senior pancreatobiliary surgeon, each trainee performed the PJ using silicone models and recorded them 10 times using a video camera. Of these videos, 5 were randomly duplicated due to the validation of the scoring system. The scoring system developed consisted of 20 scores. Three pancreatobiliary professors scored their performance by watching videos. Results: The mean procedure time of the 5 trainees was 25.4 minutes (range, 23.5-27.3 minutes) in the first video and 15.8 minutes (range, 13.8-19.1 minutes) in the 10th video. The mean score was 12.6 (range, 5-19) and 18.3 (range, 15-20) in the first and 10th videos, respectively. The scores were similar among the duplicated videos for each supervisor. Conclusion: This education system would help pancreatobiliary trainees to overcome learning curves efficiently without ethical issues related to animal models or direct practice to human patients.

A retrospective multicentre study on the evaluation of perioperative outcomes of single-port robotic cholecystectomy comparing the Xi and SP versions of the da Vinci robotic surgical system.

BACKGROUND: Single-incision robotic cholecystectomy (SIRC) is widely performed with both the da Vinci Xi system (Xi) and the da Vinci SP system (SP). But there are limited numbers of studies comparing these platforms. METHODS: Patients who underwent SIRC between 2019 and 2020 were enrolled. Patient demographics, intraoperative factors, postoperative complications, postoperative pain were compared using a one-to-one propensity score matching (PSM). RESULTS: Overall, 258 patients underwent SIRC with Xi and 72 with SP. After PSM, there were significant differences between the Xi and SP in operation time at console and numeric rating scale for postoperative pain, but no difference in total operation time and postoperative complications. The SP group showed more estimated blood loss. CONCLUSIONS: Despite the statistical difference, clinical benefit was not significant. Both platforms can be safe and feasible to perform SIRC, but further investigation including the surgeon's workload and ergonomics is needed as a prospective study.