Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in ...pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio OR: 3.80 1.92-7.51, P = .0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 0.88-6.58, P = .087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 2.74-18.01, P = .0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 1.58-8.39, P < .023) and CPB1 (OR: 9.51 3.46-26.15, P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Though robotic pancreaticoduodenectomy(R‐PD) is gradually adopted, learning curve and its feasibility is still controversial. We analyzed our first 70 R‐PD cases, comparing surgical ...outcomes and feasibility to those of open pancreaticoduodenectomy (O‐PD).
Methods
Medical records of 70 patients of R‐PD and 269 patients of O‐PD between 2015 and 2019 were retrospectively analyzed. Cumulative sum analysis was used to determine learning curve. Surgical outcomes were compared between early(1‐35) and late cases(36‐70). Additional analyses with O‐PD using propensity score‐matching were done.
Results
Learning curve of R‐PD completed after 30 cases. Shorter operative time, lower estimated blood loss, and shorter length of stay were noted in later cases. Complication rate tended to decrease over time. In comparison with O‐PD after matching, R‐PD showed longer operation time(414.5 minutes vs 244.7 minutes; P < .001), with no differences in estimated blood loss, or length of stay. While overall complication rate was higher in R‐PD(45.5% vs 21.8%; P = .010), no statistically significant difference was observed in major complication rates(23.6% vs 10.9%; P = .084). R0 rate was equivalent.
Conclusion
Surgical performance of R‐PD improved over time. Learning curve of R‐PD completed after 30 cases. R‐PD is a promising modality, based on comparison of perioperative and oncologic feasibilities to those of O‐PD.
HighlightKim and colleagues analyzed the first 70 cases of robotic pancreaticoduodenectomy performed by a single surgeon at a single institution. The learning curve, analyzed on the basis of operative time, was completed after 30 cases. Perioperative outcomes and oncologic feasibility of robotic pancreaticoduodenectomy were comparable to those of open pancreaticoduodenectomy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Background The long-term prognosis of patients with variant angina presenting with aborted sudden cardiac death (ASCD) is unknown. Objectives The purpose of this study was to evaluate the ...long-term mortality and ventricular tachyarrhythmic events of variant angina with and without ASCD. Methods Between March 1996 and September 2014, 188 patients with variant angina with ASCD and 1,844 patients with variant angina without ASCD were retrospectively enrolled from 13 heart centers in South Korea. The primary endpoint was cardiac death. Results Predictors of ASCD manifestation included age (odd ratio OR: 0.980 by 1 year increase; 95% confidence interval CI: 0.96 to 1.00; p = 0.013), hypertension (OR: 0.51; 95% CI: 0.37 to 0.70; p < 0.001), hyperlipidemia (OR: 0.38; 95% CI: 0.25 to 0.58; p < 0.001), family history of sudden cardiac death (OR: 3.67; 95% CI: 1.27 to 10.6; p = 0.016), multivessel spasm (OR: 2.06; 95% CI: 1.33 to 3.19; p = 0.001), and left anterior descending artery spasm (OR: 1.40; 95% CI: 1.02 to 1.92; p = 0.04). Over a median follow-up of 7.5 years, the incidence of cardiac death was significantly higher in ASCD patients (24.1 per 1,000 patient-years vs. 2.7 per 1,000 patient-years; adjusted hazard ratio HR: 7.26; 95% CI: 4.21 to 12.5; p < 0.001). Death from any cause also occurred more frequently in ASCD patients (27.5 per 1,000 patient-years vs. 9.6 per 1,000 patient-years; adjusted HR: 3.00; 95% CI: 1.92 to 4.67; p < 0.001). The incidence rate of recurrent ventricular tachyarrhythmia in ASCD patients was 32.4 per 1,000 patient-years, and the composite of cardiac death and ventricular tachyarrhythmia was 44.9 per 1,000 patient-years. A total of 24 ASCD patients received implantable cardioverter-defibrillators (ICDs). There was a nonsignificant trend of a lower rate of cardiac death in patients with ICDs than those without ICDs (p = 0.15). Conclusions The prognosis of patients with variant angina with ASCD was worse than other patients with variant angina. In addition, our findings supported ICDs in these high-risk patients as a secondary prevention because current multiple vasodilator therapy appeared to be less optimal.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The efficacy and outcomes of laparoscopic resection for pancreatic neuroendocrine tumors (PNETs) are well established; however, specific data regarding the outcomes of laparoscopic ...pancreaticoduodenectomy (L-PD) are limited. The purpose of the present study was to compare the clinical and oncological outcomes following L-PD versus open PD (O-PD) in patients with PNETs.
Methods
This retrospective study included 149 patients with PNETs who underwent PD at the Asan Medical Center between January 2006 and December 2017. In 58 patients, a laparoscopic approach was used (L-PD group), and in 91, an open technique was used (O-PD group).
Results
The mean operative time was longer in the L-PD group than in the O-PD group (417.4 min vs. 362.2 min;
p
= 0.002), and the mean duration of postoperative stay was shorter in the L-PD group (12.6 days vs. 17.8 days;
p
< 0.001). The estimated blood loss (433.2 ml vs. 415.0 ml
; p
= 0.824) and the overall complication rate (34.5% vs. 38.5%;
p
= 0.624) did not significantly differ between the two groups. Regarding the oncological outcomes, there were no significant differences in the resection margins, tumor size, tumor grading, or T/N stage. The number of harvested lymph nodes in the L-PD group was lower than that in the O-PD group (7.1 vs. 10.8;
p
= 0.002). The 3-year overall survival rate was 91.9% in the L-PD group and 93.6% in the O-PD group (
p
= 0.974). The 3-year disease-free survival rate was 94.8% in the L-PD group and 86.7% in the O-PD group (
p
= 0.225).
Conclusions
L-PD is feasible for the treatment of PNETs in selected patients and has the advantages of short recovery time and reduced hospital stay. The survival rate was similar in both groups; however, due to the difference in the harvested lymph nodes, a randomized trial should confirm the oncological safety of L-PD for PNETs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background Although laparoscopic surgery has many advantages, its application in pancreatic ductal adenocarcinoma has not been sufficiently studied. The objective of this study was to compare the ...surgical outcomes of laparoscopic distal pancreatectomy (LDP) to those of open distal pancreatectomy (ODP) for left-sided ductal adenocarcinoma. Study Design Among 167 consecutive patients between December 2006 and August 2013, 150 patients were included. Unmatched and propensity score-matched analyses were performed to compare the primary (oncologic adequacy) and secondary outcomes (hospital course and complications) between ODP and LDP groups. Results In unmatched patients, LDP was associated with an earlier return to diet and a shorter hospital stay compared with ODP. The 5-year survival rates were 27.6% in unmatched ODP (n = 80) and 32.5% in unmatched LDP (n = 70). Fifty-one patients from each group were selected by propensity score matching. In this matched patient comparison, LDP was again associated significantly with a shorter median postoperative time to restarting diet and a shorter hospital stay. The 2 groups did not differ significantly in terms of primary outcomes of operative time, number of harvested lymph nodes, resection margin status, and secondary outcomes of frequency of pancreatic fistula and complications. The 2 groups also had comparable patient survival (p = 0.91). Conclusions This large single-center study of laparoscopic surgery for left-sided pancreatic ductal adenocarcinoma indicated that LDP was safe and more efficacious than OPD after propensity score adjustment for presurgical variables of return to diet and length of stay.
This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database ...for IPMN.
Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited.
Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded.
The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test.
A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
Background
Extranodal extension (ENE) is an established prognostic factor in several gastrointestinal cancers. However, the prognostic impact remains unclear. Here, we investigated the prognostic ...implications of ENE in patients with surgically resected pancreatic cancer.
Methods
We retrospectively reviewed 476 surgically resected pancreatic head cancer patients who consecutively underwent upfront pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. We compared the disease‐free survival (DFS) rates of the patients according to ENE status.
Results
Among the 476 patients, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; LN+/ENE−, 7 months; LN+/ENE+, 6 months; P < .001). In addition, even in the same N stage, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; N1/ENE− 8 months; N1/ENE+, 7 months; N2/ENE−, 7 months; N2/ENE+, 4 months, P < .001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and those in the N2/ENE− group. Additionally, ENE was an independent prognostic factor for pancreatic cancer.
Conclusions
Extranodal extension significantly predicted a poor prognosis among patients with pancreatic head cancer, especially those with nodal metastasis. Therefore, ENE should be considered a prognostic factor in future editions of the staging system.
In this study, Sung and colleagues showed that extranodal extension was a significant prognostic factor in patients with pancreatic head cancer. In subgroup analysis according to each AJCC stage, patients with extranodal extension had worse survival than those without. Extranodal extension should be considered when developing a new staging system.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background/Purpose
The pathophysiology and associated factors of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) remain elusive. We aimed to investigate these factors, ...including the operation type, for NAFLD development after PD.
Methods
This historical cohort study included 786 consecutive patients treated with either classic Whipple operation or pylorus‐preserving pancreaticoduodenectomy (PPPD) in Korea between 2012 and 2018. De novo NAFLD was determined based on hepatic attenuation in nonenhanced computed tomography during follow‐up.
Results
Of the 786 patients, 216 (27.5%) had a newly developed NAFLD at 2 years after PD. The incidences of newly developed NAFLD at 0.5, 1, 1.5, and 2 years were 13 (1.7%), 41 (5.2%), 48 (6.1%), and 114 (14.5%), respectively. The Whipple group showed a significantly higher incidence of NAFLD than the PPPD group (40.3% vs 24.5%, P < .001). Seventeen patients (2.2%) had severe fatty liver with abnormal liver enzymes. Multivariable analysis revealed that Whipple operation (vs PPPD; adjusted odds ratio AOR: 1.92, P < .001) and high preoperative body mass index (vs normal; AOR: 1.71, P = .001) were independently associated with a higher risk of NAFLD.
Conclusion
The incidence of NAFLD was 27.5% at 2 years after PD. Undergoing Whipple operation and high preoperative body mass index were significantly associated with de novo NAFLD development.
One of the postoperative complications after pancreaticoduodenectomy is de novo development of non‐alcoholic fatty liver disease. In this large cohort study of 786 patients, Jeon et al found high preoperative body mass index and Whipple's operation, as opposed to pylorus‐preserving pancreaticoduodenectomy, to be associated with newly developed non‐alcoholic fatty liver disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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