Publications by authors named "Yejong Park"

32 Publications

The clinicopathologic and operative characteristics of patients with small nonfunctioning pancreatic neuroendocrine tumors.

ANZ J Surg 2021 Jul 21. Epub 2021 Jul 21.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.

Background: Incidentally detected, small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed on imaging modalities. This retrospective investigation evaluated the clinicopathologic characteristics and perioperative and oncologic outcomes in patients with small NF-PNETs undergoing curative resection.

Methods: The medical records of 444 patients who underwent pancreatic resection for NF-PNETs at a single, large-volume institution between January 2000 and December 2018 were retrospectively reviewed. Patients were divided into those with small (≤2 cm) and large (>2 cm) tumors based on the largest tumor diameter on preoperative computed tomography (CT). Outcomes were also evaluated in subgroups of patients with small NF-PNET who did and did not undergo lymphadenectomy.

Results: Of the 444 patients with NF-PNETs, 195 (43.9%) had small (≤2 cm) and 249 (56.1%) had large (>2 cm) NF-PNETs. The rate of parenchyma-preserving surgery (14.4% vs. 7.2%, p = 0.014) and the ratio of spleen preservation for left-sided pancreatectomy (65.6% vs. 38.3%, p < 0.001) were higher in the small NF-PNET group. Size on CT >2 cm (p < 0.001, hazard ratio [HR]: 5.836, 95% confidence interval [CI]: 2.474-13.769), presence of perineural invasion (p < 0.001, HR: 3.025, 95% CI: 1.640-5.577), World Health Organization (WHO) Grade 2 (p = 0.007, HR: 2.861, 95% CI: 1.325-6.176), and WHO Grade 3 (p < 0.001, HR: 11.537, 95% CI: 5.282-25.199) were independent predictors of disease-free survival (DFS). DFS did not differ significantly in patients with small NF-PNETs who did and did not undergo lymphadenectomy (p = 0.886).

Conclusions: Assessment of long-term oncologic outcomes suggests that surgical resection may cure small NF-PNETs. Minimally invasive surgery and organ-preserving surgery are acceptable treatment options for select patients with small NF-PNETs. The effect on survival outcomes of lymph node dissection for small NF-PNETs remains unclear.
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http://dx.doi.org/10.1111/ans.17055DOI Listing
July 2021

Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage.

J Control Release 2021 Jul 10;335:650-659. Epub 2021 Jun 10.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Division of Hepatobiliary Pancreas Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea; Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.010DOI Listing
July 2021

Prognostic Impact of Perioperative CA19-9 Levels in Patients with Resected Perihilar Cholangiocarcinoma.

J Clin Med 2021 Mar 24;10(7). Epub 2021 Mar 24.

Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

We aimed to examine the predictive value of changes in perioperative carbohydrate antigen (CA) 19-9 levels for patients operated for perihilar cholangiocarcinoma (pCCA). A total of 322 patients who underwent curative resection for pCCA were divided into three groups: normal preoperative CA19-9 (CA19-9 ≤ 37 U/mL), normalization (preoperative CA19-9 > 37 U/mL, postoperative CA19-9 ≤ 37 U/mL), and non-normalization (pre- and postoperative CA19-9 > 37 U/mL) groups. The association of clinicopathological factors with overall survival (OS) was investigated. The non-normalization group ( = 82) demonstrated significantly worse OS than the normal CA19-9 ( = 114) and normalization ( = 126) groups (5-year OS, 16.9%, 29.4%, and 34.4%, respectively; both ≤ 0.001). The cutoff points of 300 U/mL for preoperative ( = 0.001) and 37 U/mL for postoperative ( < 0.001) CA19-9 levels showed the strongest prognostic values. In the non-normalization group, patients who underwent R1 resection displayed significantly worse OS than those who underwent R0 resection (median OS, 10.2 vs. 15.7 months; = 0.016). Multivariate analysis revealed that lymph node metastasis (hazard ratio (HR), 2.07; < 0.001), postoperative CA19-9 > 37 U/mL (HR, 1.94; < 0.001), transfusion (HR, 1.74; = 0.002), and T stage (T3,4) (HR, 1.67; = 0.006) were related to worse OS. Persistent high CA19-9 level after resection of pCCA and R1 resection, especially in the non-normalization group, was associated with poor OS. A high postoperative CA19-9 level was an independent prognostic factor in resected pCCA.
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http://dx.doi.org/10.3390/jcm10071345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036534PMC
March 2021

Lack of Association between Postoperative Pancreatitis and Other Postoperative Complications Following Pancreaticoduodenectomy.

J Clin Med 2021 Mar 11;10(6). Epub 2021 Mar 11.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Background: Prediction of post-pancreaticoduodenectomy (PD) morbidity is difficult, especially in the early postoperative period when CT (Computed Tomography) scans are not available. Elevated serum amylase and lipase in postoperative day 0 or 1 may be used to define postoperative acute pancreatitis (POAP), but the existing literature does not agree on whether POAP is significantly associated with postoperative pancreatic fistula (POPF).

Methods: We analyzed the data obtained from a previously published randomized controlled trial. POAP was defined as elevations in serum amylase above 110 U/L on postoperative day 0 or 1. Clinically relevant POAP (CR-POAP) was defined as elevations in C-reactive protein level (CRP) on postoperative day 2 in those with POAP. Postoperative complications including severe complications (Clavien-Dindo ≥ IIIa), POPF, and clinically relevant POPF (CR-POPF) were analyzed.

Results: In 246 patients, POAP did not show significant associations with total postoperative complications (odds ratio (OR) 0.697; 95% CI, 0.360-1.313; = 0.271), severe complications (OR 0.647; 95% CI, 0.258-1.747; = 0.367), and CR-POPF (OR 0.998; 95% CI, 0.310-3.886; = 0.998) in multivariable analysis.

Conclusions: In patients undergoing PD, POAP was not significantly associated with postoperative complications including POPF. Caution should be taken when using POAP as a predictor of POPF.
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http://dx.doi.org/10.3390/jcm10061179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001526PMC
March 2021

Circulating tumour cells as an indicator of early and systemic recurrence after surgical resection in pancreatic ductal adenocarcinoma.

Sci Rep 2021 Jan 18;11(1):1644. Epub 2021 Jan 18.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Early recurrence in pancreatic ductal adenocarcinoma (PDAC) is a decisive factor in determining a patient's prognosis. We determined in our current study whether circulating tumour cells (CTCs) exist in the blood of PDAC patients and can be used as a predictor of recurrence patterns (i.e. time and site) after surgical resection. Between December 2017 and November 2018, the mononuclear cell layer was obtained from the peripheral blood of 36 patients diagnosed with PDAC. CTCs were then isolated using the CD-PRIME™ platform and detected via immunostaining. The patient records were analyzed to correlate these data with survival and recurrence patterns. Twelve patients were CTC-positive (33.3%) and showed a significantly frequent rate of systemic recurrence (distant metastases and peritoneal dissemination) (p = 0.025). On multi-variable logistic regression analysis, CTC positivity was an independent risk factor for early recurrence (p = 0.027) and for systemic recurrence (p = 0.033). In summary, the presence or absence of CTC in the blood of the patients with PDAC could help predict the recurrence pattern after surgery. PDAC patients with CTC positivity at tumour diagnosis should therefore undergo a comprehensive strategy for systemic therapy and active monitoring to detect possible early recurrence.
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http://dx.doi.org/10.1038/s41598-020-80383-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814057PMC
January 2021

Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients.

Cancer Res Treat 2021 Apr 9;53(2):424-435. Epub 2020 Nov 9.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.

Materials And Methods: Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.

Results: The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).

Conclusion: AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.
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http://dx.doi.org/10.4143/crt.2020.953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053873PMC
April 2021

A comparison of minimally invasive vs open distal pancreatectomy for resectable pancreatic ductal adenocarcinoma: Propensity score matching analysis.

J Hepatobiliary Pancreat Sci 2020 Oct 22. Epub 2020 Oct 22.

Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan college of Medicine, Seoul, South Korea.

Background: Owing to concerns regarding adequate oncological outcomes and perioperative complications, minimally invasive distal pancreatectomy (MIDP) for pancreatic ductal adenocarcinoma (PDAC) has limited generalizability. The aim of this study was to assess the perioperative and oncologic outcomes of MIDP compared with open distal pancreatectomy (ODP) for resectable PDAC after propensity score matching (PSM).

Methods: The patients who underwent MIDP and ODP for PDAC between January 2010 and December 2017 were retrospectively reviewed. Demographics, perioperative outcomes, pathological outcomes, and overall and disease-free survival data were collected to compare MIDP and ODP. After PSM, perioperative and oncologic outcomes were analyzed.

Results: A total of 156 MIDP patients were compared with 156 ODP patients for resectable PDAC after PSM. Tumor size, TNM stage, differentiation, harvested lymph nodes, and positive lymph nodes were not different except for R1 resection and lymphovascular invasion between the MIDP and ODP groups. Operation times, overall complications, POPF, and adjuvant treatment were also not different between the two groups. The MIDP group had shorter hospital stays (10.0 vs 13.4 days, P < 0.001) and shorter interval times from surgery to adjuvant treatment (37.6 days vs 46.0 days, P = 0.002) than the ODP group. The MIDP group had better overall survival (34.9 vs 24.5 months, P = 0.012) and disease-free survival (16.2 vs 10.3 months, P = 0.001).

Conclusion: Minimally invasive distal pancreatectomy has advantages with respect to postoperative hospital stay, interval between surgery, and adjuvant treatment. MIDP is associated with the possibility of improved survival rate for resectable PDAC.
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http://dx.doi.org/10.1002/jhbp.853DOI Listing
October 2020

Assessment of learning curve and oncologic feasibility of robotic pancreaticoduodenectomy: A propensity score-based comparison with open approach.

J Hepatobiliary Pancreat Sci 2020 Oct 15. Epub 2020 Oct 15.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.

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.
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http://dx.doi.org/10.1002/jhbp.837DOI Listing
October 2020

Effect of Flowable Thrombin-Containing Collagen-Based Hemostatic Matrix for Preventing Pancreatic Fistula after Pancreatectomy: A Randomized Clinical Trial.

J Clin Med 2020 Sep 24;9(10). Epub 2020 Sep 24.

Division of Hepato-Biliary Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine & Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Background: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy.

Methods: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay.

Results: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453-207.870, p = 0.024).

Conclusion: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.
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http://dx.doi.org/10.3390/jcm9103085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601002PMC
September 2020

Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

Medicine (Baltimore) 2020 Sep;99(37):e22115

Division of Hepato-biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center.

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12-26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04).Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.
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http://dx.doi.org/10.1097/MD.0000000000022115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489745PMC
September 2020

Predictive Factors Associated with Complications after Laparoscopic Distal Pancreatectomy.

J Clin Med 2020 Aug 26;9(9). Epub 2020 Aug 26.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Although laparoscopic distal pancreatectomy (LDP) has become more popular, the postoperative complication rate remains high. We sought to identify the risk factors for post-LDP complications. We examined 1227 patients who underwent LDP between March 2005 and December 2015 at a single large-volume center. We used logistic regression for the analysis. The overall (13.2%) and major (3.3%) complication rates were determined. Postoperative pancreatic fistula was the most frequent complication, and 58 patients (4.7%) had clinically significant (grade B) pancreatic fistulas. No 90-day mortality was recorded. Long operative time (≥200 min), large estimated blood loss (≥320 mL), LDP performed by an inexperienced surgeon (<50 cases), and concomitant splenectomy were identified as risk factors for overall complications using a logistic regression model. For major complications, male sex ( = 0.020), long operative time ( = 0.005), and LDP performed by an inexperienced surgeon ( = 0.026) were significant predictive factors. Using logistic regression analysis, surgery-related factors, including long operative time and LDP performed by an inexperienced surgeon, were correlated with overall and major complications of LDP. As LDP is a technically challenging procedure, surgery-related variables emerged as the main risk factors for postoperative complications. Appropriate patient selection and sufficient surgeon experience may be essential to reduce the complications of LDP.
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http://dx.doi.org/10.3390/jcm9092766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563868PMC
August 2020

Surgical Decisions Based on a Balance between Malignancy Probability and Surgical Risk in Patients with Branch and Mixed-Type Intraductal Papillary Mucinous Neoplasm.

J Clin Med 2020 Aug 26;9(9). Epub 2020 Aug 26.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Korea.

Objective: To propose a decision tool considering both malignancy probability and surgical risk for intraductal papillary mucinous neoplasm (IPMN). Background Data Summary: Surgical risk and malignancy probability are both critical factors in making decisions about surgical resection of IPMN.

Methods: We included 800 patients who underwent pancreatic resection for branch duct and mixed-type IPMN (April 1995 to June 2018). A nomogram was used to obtain the malignancy probability (MP-N). The surgical risks were estimated as the postoperative complication rate and serious complication from the ACS NSQIP surgical risk calculator (SC-ACS NSQIP). The risk-benefit analysis was conducted in two ways: calculation of the cutoff value of MP-N using the complication rate and directly comparing the MP-N and SC-ACS NSQIP results.

Results: The optimal cutoff value of MP-N was 32% and 21% in the pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) groups, respectively, when using the major complication rate (Clavien grades III over). When we applied the optimal cutoff value to the two surgical methods, surgery was reduced by 51.7% in the PD group and 56% in the DP group, and the AUC value of the malignant predictions were 0.7126 and 0.7615, respectively. According to the direct comparison of MP-N and SC-ACS NSQIP, surgery was reduced by 31.7%, and the AUC value of malignant prediction was 0.6588.

Conclusion: Our risk-benefit analysis model considering both malignancy probability and surgical risk is relatively acceptable, and it may help surgeons and patients make treatment decisions for a disease with a broad spectrum of malignancy rates.
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http://dx.doi.org/10.3390/jcm9092758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565903PMC
August 2020

The identification of candidate effective combination regimens for pancreatic cancer using the histoculture drug response assay.

Sci Rep 2020 07 20;10(1):12004. Epub 2020 Jul 20.

Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, 388-1 Pungnap-2 Dong, Songpa-gu, Seoul, 05505, South Korea.

The prognosis for patients with pancreatic cancer is extremely poor, as they are resistant to first line chemotherapy. The long-term goal of this study was to identify effective combination chemotherapy for pancreatic cancer using pancreatic cancer surgical specimens in the histoculture drug response assay (HDRA) based on three-dimensional culture of tumour fragments, which maintains nature tumour histology in vitro. From 2015 to 2017, the HDRA was performed with tumour specimens from 52 pancreatic cancer patients from Asan Medical Hospital. First, combination drug regimens showed higher drug efficacy and less patient variation than single drugs. Initially, 5-Fluorouracil(5-FU)/Belotecan/Oxaliplatinum and Tegafur/Gimeracil (TS-1)/Oxaliplatinum/Irinotecan were found to be effective. Second, we were able to correlate the efficacy of some drugs with tumour stage. Third, when designing new combination regimens containing 5-FU or gemcitabine, we could identify more effective drug combinations. This is the first study to demonstrate usefulness of the HDRA for pancreatic cancer. Using this technique, we could identify novel candidate combination drug regimens that should be effective in treating pancreatic cancer.
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http://dx.doi.org/10.1038/s41598-020-68703-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371642PMC
July 2020

A Comparative Study of Laparoscopic versus Open Pancreaticoduodenectomy for Ampulla of Vater Carcinoma.

J Clin Med 2020 Jul 13;9(7). Epub 2020 Jul 13.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Several studies have compared laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with periampullary carcinoma; however, only a few studies have made such a comparison on patients with ampulla of Vater cancer (AVC). We compared the perioperative and oncologic outcomes between LPD and OPD in patients with AVC using propensity-score-matched analysis. A total of 359 patients underwent PD due to AVC during the study period (76 LPD, 283 OPD). After propensity score matching, the LPD group showed significantly longer operation time than did the OPD group (400.2 vs. 344.6 min, < 0.001). Nevertheless, the LPD group had fewer painkiller administrations (8.3 vs. 11.1, < 0.049), fewer Grade II or more severe postoperative complications (15.9% vs. 34.8%, = 0.012), and shorter postoperative hospital stays (13.7 vs. 17.3 days, = 0.048), compared with the OPD group. There was no significant difference in recurrence-free outcomes and overall survival between the two groups ( = 0.754 and 0.768, respectively). Compared with OPD, LPD for AVC had comparative oncologic outcomes with less pain, less postoperative morbidity, and shorter hospital stays. LPD may serve as a promising alternative to OPD in patients with AVC.
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http://dx.doi.org/10.3390/jcm9072214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408711PMC
July 2020

Association between Metformin Use and Clinical Outcomes Following Pancreaticoduodenectomy in Patients with Type 2 Diabetes and Pancreatic Ductal Adenocarcinoma.

J Clin Med 2020 Jun 22;9(6). Epub 2020 Jun 22.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Retrospective studies on the association between metformin and clinical outcomes have mainly been performed on patients with non-resectable pancreatic ductal adenocarcinoma and may have been affected by time-related bias. To avoid this bias, recent studies have used time-varying analysis; however, they have only considered the start date of metformin use and not the stop date. We studied 283 patients with type 2 diabetes and pancreatic ductal adenocarcinoma following pancreaticoduodenectomy, and performed analysis using a Cox model with time-varying covariates, while considering both start and stop dates of metformin use. When start and stop dates were not considered, the metformin group showed significantly better survival. Compared with previous studies, adjusted analysis based on Cox models with time-varying covariates only considering the start date of postoperative metformin use showed no significant differences in survival. However, although adjusted analysis considering both start and stop dates showed no significant difference in recurrence-free survival, the overall survival was significantly better in the metformin group (Hazard ratio (HR), 0.747; 95% confidence interval (CI), 0.562-0.993; = 0.045). Time-varying analysis incorporating both start and stop dates thus revealed that metformin use is associated with a higher overall survival following pancreaticoduodenectomy in patients with type 2 diabetes and pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.3390/jcm9061953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356590PMC
June 2020

Risk factors of posthepatectomy liver failure for perihilar cholangiocarcinoma: Risk score and significance of future liver remnant volume-to-body weight ratio.

J Surg Oncol 2020 Sep 18;122(3):469-479. Epub 2020 May 18.

Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Surgery for perihilar cholangiocarcinoma (PHCC) is associated with high morbidity. This study aimed to investigate the clinical value of the future liver remnant volume-to-body weight (FLRV/BW) and propose a risk score for predicting the risk of patients with PHCC developing posthepatectomy liver failure (PHLF).

Methods: This study included 348 patients who underwent major hepatectomy with bile duct resection for PHCC during 2008-2015 at a single center in Korea and they were retrospectively analyzed.

Results: Clinically relevant PHLF was noted in 40 patients (11.4%). The area under the curve (AUC) for FLRV/BW was not significantly different from that for FLRV/total liver volume (P = .803) or indocyanine green clearance of the future liver remnant (P = .629) in terms of predicting PHLF. On multivariate analysis, predictors of PHLF (P < .05) were male sex, albumin less than 3.5 g/dL, preoperative cholangitis, portal vein resection, FLRV/BW less than 0.5%, and FLRV/BW 0.5% to 0.75%. These variables were included in the risk score that showed good discrimination (AUC, 0.853; 95% CI, 0.802-0.904). It will help rank patients into three risk subgroups with a predicted liver failure incidence of 4.75%, 18.73%, and 51.58%, respectively.

Conclusions: FLRV/BW is a comparable risk prediction factor of PHLF and the proposed risk score can help to predict the risk of planned surgery in PHCC.
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http://dx.doi.org/10.1002/jso.25974DOI Listing
September 2020

Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer.

J Clin Med 2020 May 14;9(5). Epub 2020 May 14.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC).

Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC).

Results: CA 19-9 concentrations of 37-1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092-0.748; = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093-0.739; = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140-0.642; = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences.

Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.
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http://dx.doi.org/10.3390/jcm9051477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291310PMC
May 2020

Comparison of Minimally Invasive Versus Open Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Propensity Score Matching Analysis.

Cancers (Basel) 2020 Apr 15;12(4). Epub 2020 Apr 15.

Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea.

Few studies have compared perioperative and oncological outcomes between minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC). : A retrospective review of patients undergoing MIPD and OPD for PDAC from January 2011 to December 2017 was performed. Perioperative, oncological, and survival outcomes were analyzed before and after propensity score matching (PSM). : Data from 1048 patients were evaluated (76 MIPD, 972 OPD). After PSM, 73 patients undergoing MIPD were matched with 219 patients undergoing OPD. Operation times were longer for MIPD than OPD (392 vs. 327 min, < 0.001). Postoperative hospital stays were shorter for MIPD patients than OPD patients (12.4 vs. 14.2 days, = 0.040). The rate of overall complications and postoperative pancreatic fistula did not differ between the two groups. Adjuvant treatment rates were higher following MIPD (80.8% vs. 59.8%, = 0.002). With the exception of perineural invasion, no differences were seen between the two groups in pathological outcomes. The median overall survival and disease-free survival rates did not differ between the groups. : MIPD showed shorter postoperative hospital stays and comparable perioperative and oncological outcomes to OPD for selected PDAC patients. Future randomized studies will be required to validate these findings.
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http://dx.doi.org/10.3390/cancers12040982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226374PMC
April 2020

Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with the 7th Staging System.

Cancer Res Treat 2020 Jul 12;52(3):886-895. Epub 2020 Mar 12.

Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: This study was conducted to evaluate the prognostic values of the 7th and 8th American Joint Committee on Cancer (AJCC) staging systems for patients with resected perihilar cholangiocarcinoma (PHCC).

Materials And Methods: A total of 348 patients who underwent major hepatectomy for PHCC between 2008 and 2015 were identified from a single center. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index was used to evaluate the prognostic predictability of the 8th AJCC staging system compared with that of the 7th.

Results: In the 8th edition, the stratification of each group of T classification improved compared to that in the 7th, as the survival rate of T4 decreased (T2, 31.2%; T3, 13.9%; T4, 15.1%; T1-T2, p=0.260; T2-T3, p=0.001; T3-T4, p=0.996). Both editions showed significant survival differences between each N category, except between N1 and N2 (p=0.063) in 7th edition. Differences of point estimates between the 8th and 7th T and N classification and overall stages were +0.028, +0.006, and +0.039, respectively (T, p=0.005; N, p=0.115; overall stage, p=0.005). In multivariable analysis, posthepatectomy liver failure, T category, N category, distant metastasis, histologic differentiation, intraoperative transfusion, and resection margin status were associated with OS.

Conclusion: The prognostic predictability of 8th AJCC staging for PHCC improved slightly, with statistical significance, compared to the 7th edition, but its overall performance is still unsatisfactory.
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http://dx.doi.org/10.4143/crt.2020.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373861PMC
July 2020

Analysis of Symptomatic Marginal Ulcers in Patients Who Underwent Pancreaticoduodenectomy for Periampullary Tumors.

Pancreas 2020 02;49(2):208-215

From the Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery.

Object: The objectives are to investigate the incidence and risk factors associated with symptomatic marginal ulcer (sMU) and analyze their relationship with the use of prophylactic proton pump inhibitors (PPIs) after pancreaticoduodenectomy.

Methods: Clinical postoperative outcomes of 72 sMU and 1266 non-sMU were compared and analyzed. We performed a subanalysis of 72 patients with sMU diagnosed within (n = 18) and after 4 months (n = 54). The risk factors associated with sMU incidence were analyzed.

Results: Of the 1338 patients, 72 (5.4%) were diagnosed as having sMU. Eighteen patients (25.0%) were diagnosed during the first 4 months, and 48 (66.7%), within 16 months. Cumulative sMU incidence differed according to the duration of prophylactic PPI use (≥4 months: 7.1% vs <4 months: 10.1%, P < 0.001). The duration of prophylactic PPI use was identified as a risk factor in the multivariable analysis (hazard ratio, 2.294; 95% confidence interval, 1.436-3.664; P = 0.001).

Conclusions: Two-thirds or more of the patients were diagnosed as having sMU within 16 months after surgery. The duration of the prophylactic PPI use was an independent risk factor. We recommend the use of prophylactic PPI for more than 16 months after pancreaticoduodenectomy for periampullary tumors.
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http://dx.doi.org/10.1097/MPA.0000000000001470DOI Listing
February 2020

A Novel Biodegradable Tubular Stent Prevents Pancreaticojejunal Anastomotic Stricture.

Sci Rep 2020 01 30;10(1):1518. Epub 2020 Jan 30.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.
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http://dx.doi.org/10.1038/s41598-019-57271-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992790PMC
January 2020

Clinical outcomes of octogenarians according to preoperative disease severity and comorbidities after laparoscopic cholecystectomy for acute cholecystitis.

J Hepatobiliary Pancreat Sci 2020 Jun 29;27(6):307-314. Epub 2020 Feb 29.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/purpose: Clinical outcomes of octogenarians with acute cholecystitis treated with laparoscopic cholecystectomy are unclear. This study aimed to compare their outcomes according to preoperative severity and comorbidities.

Methods: Medical charts of 120 octogenarians who underwent laparoscopic cholecystectomy for acute cholecystitis between January 2008 and December 2017 at Asan Medical Center, Seoul, Korea, were retrospectively reviewed. Based on the Tokyo Guidelines 2018 (TG 18), patients had mild (n = 35), moderate (n = 61), or severe (n = 24) disease. We investigated postoperative outcomes, comorbidities, and prognostic factors of ≥grade III complications.

Results: Total antibiotic use duration (P = .024), operative times (P = .002), additional port insertion (P = .012), and postoperative hospital stay (P = .018) were significantly higher in the severe group. There were no statistically significant differences in total or grade III or higher complications (P = .304) or mortality (P = .476). On multivariate analysis, pulmonary disease predicted Clavien-Dindo classification ≥grade III complications (odds ratio 37.075; 95% confidence interval 5.734-239.695; P < .001).

Conclusions: In octogenarians, laparoscopic cholecystectomy is feasible and tolerable for severe acute cholecystitis classified according to the TG 18. Pulmonary comorbidities are an independent prognostic factor of ≥grade III complications.
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http://dx.doi.org/10.1002/jhbp.719DOI Listing
June 2020

Clinicopathologic and Prognostic Significance of Gallbladder and Cystic Duct Invasion in Distal Bile Duct Carcinoma.

Arch Pathol Lab Med 2020 06 22;144(6):755-763. Epub 2019 Nov 22.

From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Context.—: The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated.

Objective.—: To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC.

Design.—: Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs.

Results.—: CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size ( = .001), bile duct margin positivity ( = .001), perineural invasions ( = .04), and higher N categories ( = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times ( = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions ( .001).

Conclusions.—: Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs.
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http://dx.doi.org/10.5858/arpa.2019-0218-OADOI Listing
June 2020

Propensity score-matching analysis comparing laparoscopic and open pancreaticoduodenectomy in elderly patients.

Sci Rep 2019 09 10;9(1):12961. Epub 2019 Sep 10.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.

There is little evidence on the safety and benefits of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients; therefore, we evaluated the feasibility and efficacy of this procedure by comparing perioperative and oncological outcomes between LPD and open pancreaticoduodenectomy (OPD) in elderly patients. We retrospectively reviewed the data of 1,693 patients who underwent PD to manage periampullary tumours at a single institution between January 2014 and June 2017. Of these patients, 326 were elderly patients aged ≥70 years, with 56 patients allocated to the LPD group and 270 to the OPD group. One-to-one propensity score matching (56:56) was used to match the baseline characteristics of patients who underwent LPD and OPD. LPD was associated with significantly fewer clinically significant postoperative pancreatic fistulas (7.1% vs. 21.4%), fewer analgesic injections (10 vs. 15.6 times; p = 0.022), and longer operative time (321.8 vs. 268.5 minutes; p = 0.001) than OPD in elderly patients. There were no significant differences in 3-year overall and disease-free survival rates between the LPD and OPD groups. LPD had acceptable perioperative and oncological outcomes compared with OPD in elderly patients. LPD is a reliable treatment option for elderly patients with periampullary tumours.
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http://dx.doi.org/10.1038/s41598-019-49455-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737197PMC
September 2019

The Effect of Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil) Application in Pancreaticojejunostomy for Prevention of Pancreatic Fistula After Pancreaticoduodenectomy: A Randomized Clinical Trial.

World J Surg 2019 12;43(12):3128-3137

Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea.

Background: Fibrin sealants and topical glue have been studied to reduce the incidence of postoperative pancreatic fistulas (POPF) after pancreatico-enteric anastomosis, but a definitive innovation is still needed. We aim to evaluate the effectiveness of fibrin sealant patch applied to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF.

Methods: This study was a single-center, prospective, randomized, phase IV trial involving three pancreaticobiliary surgeons. The primary outcome was POPF; secondary outcomes included complications, drain removal days, hospital stay, readmission rate, and cost. Risk factors for POPF were identified by logistic regression analysis.

Results: A total of 124 patients were enrolled. Biochemical leakage (BL) or POPF occurred in 16 patients (25.8%) in the intervention group and 23 patients (37.1%) in the control group (no statistical significance). Clinically relevant POPF occurred in 4 patients (6.5%) in both the intervention and control groups (p = 1.000). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not statistically different between two groups. Complication rates were not different between the two groups (p = 0.506); nor were readmission rates (12.9% vs. 11.3%, p = 1.000) or cost ($13,549 vs. $15,038, p = 0.103). In multivariable analysis, age and soft pancreas texture were independent risk factors for BL or POPF in this study. Applying fibrin sealant patch is not a negative risk factor, but the p value may indicate a likelihood of reducing the incidence of BL (p = 0.084).

Conclusions: Fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF or other postoperative complications. This study was registered at clinicaltrials.gov (NCT03269955).
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http://dx.doi.org/10.1007/s00268-019-05172-yDOI Listing
December 2019

Robotic versus laparoscopic distal pancreatectomy for left-sided pancreatic tumors: a single surgeon's experience of 228 consecutive cases.

Surg Endosc 2020 06 28;34(6):2465-2473. Epub 2019 Aug 28.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background: Laparoscopic distal pancreatectomy (LDP) has gained popularity for the treatment of left-sided pancreatic tumors. Robotic systems represent the most recent advancement in minimally invasive surgical treatment for such tumors. Theoretically, robotic systems are considered to have several advantages over laparoscopic systems. However, there have been few studies comparing both systems in the treatment of distal pancreatectomy. We compared perioperative and oncological outcomes between the two treatment modalities.

Methods: A retrospective analysis was conducted of all consecutive minimally invasive distal pancreatectomy cases performed by a single surgeon at a high-volume center between January 2015 and December 2017.

Results: The analysis included 228 consecutive patients (LDP, n = 182; Robotic-assisted laparoscopic distal pancreatectomy [R-LDP], n = 46). Operative time was significantly longer in the R-LDP group than in the LDP group (166.4 vs. 140.7 min; p = 0.001). In a subgroup analysis of patients who underwent the spleen-preserving approach, the spleen preservation rate associated with R-LDP was significantly higher than that associated with LDP (96.8% vs. 82.5%; p = 0.02). In another subgroup analysis of patients with pancreatic cancer, there were no significant differences in median overall and disease-free survival between the two groups.

Conclusions: R-LDP is a safe and feasible approach with perioperative and oncological outcomes comparable to those of LDP. R-LDP offers an added technical advantage that enables the surgeon to perform a complex procedure with good ergonomic comfort.
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http://dx.doi.org/10.1007/s00464-019-07047-8DOI Listing
June 2020

Laparoscopic pancreaticoduodenectomy for periampullary tumors: lessons learned from 500 consecutive patients in a single center.

Surg Endosc 2020 03 18;34(3):1343-1352. Epub 2019 Jun 18.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background: Laparoscopic pancreaticoduodenectomy (LPD) is a feasible option in selected patients. However, its use has not yet been generalized since it is time-consuming, physically demanding, and technically challenging. It might be essential to share the experience of high-volume centers to understand its use.

Methods: We retrospectively reviewed the data of 500 consecutive patients who underwent LPD at a single institution between January 2007 and December 2017.

Results: The patients included 272 women and 228 men (mean age, 57.1 years). The most common indication for LPD was intraductal papillary neoplasm (n = 104, 20.8%). Overall and major (Clavien-Dindo grades III-V) complication rates were 37.2% and 4.8%, respectively. Fifty-four patients (10.8%) had clinically relevant (grade B/C) pancreatic fistulas. There were 3 (0.6%) 90-day mortalities. The most common late complication was bilioenteric stricture (25, 5%). Two hundred thirty patients were diagnosed with periampullary cancer. The 5-year overall survival rates of pancreatic cancer, common bile duct cancer, ampulla of Vater cancer, and duodenal cancer were 37.4, 63.2, 78, and 88.9%, respectively. We analyzed learning curves of first-generation and second-generation surgeons. A risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 cases for LPD with the first-generation surgeon and earlier competency with the second-generation surgeon.

Conclusions: LPD has the potential to become an alternative surgery to open pancreaticoduodenectomy for periampullary tumors with acceptable outcomes. We could reduce the steep learning curve with structured training, close supervision, and well-trained operation teams. Perioperative and oncologic outcomes of LPD will be optimized after overcoming the learning curve.
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http://dx.doi.org/10.1007/s00464-019-06913-9DOI Listing
March 2020

Prognostic comparison of the longitudinal margin status in distal bile duct cancer: R0 on first bile duct resection versus R0 after additional resection.

J Hepatobiliary Pancreat Sci 2019 May 8;26(5):169-178. Epub 2019 Apr 8.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background: This study investigated survival differences following intra-operative frozen-section examination of bile duct resection margins and final longitudinal margin status (LMS) in distal bile duct cancer (BDC).

Methods: One hundred and ninety-three patients underwent Whipple's operation for curative resection of distal BDC from 2008 to 2016. Patients were sorted into two and three groups according to LMS of the frozen-sections and the final pathological specimen results: R0 on first bile duct resection (primary R0), R0 after additional resection (secondary R0), and no evidence of residual carcinoma (FR0), carcinoma in situ or high-grade dysplasia (FR1-CIS/HGD), or invasive carcinoma (FR1-INV). Survival and prognostic factors according to LMS were analyzed.

Results: The final R0 ratio increased from 82.3% to 90.1% through additional resection. The 5-year overall survival (OS) of primary and secondary R0 were 60.8%, 46.1% (P = 0.969). And disease-free survival of primary and secondary R0 were 54.6%, 54.9% (P = 0.903). The 5-year OS after FR0, FR1-CIS/HGD, FR1-INV were 59.3%, 59.5%, 14.3% (P = 0.842). LMS of the bile duct was an independent prognostic factor by multivariable analyses.

Conclusions: If R0 of final LMS was achieved, it would help to improve survival regardless of R0 through additional resection. And, it should be avoided remaining invasive cancer at the longitudinal margin whenever possible.
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http://dx.doi.org/10.1002/jhbp.619DOI Listing
May 2019

Prognostic Value of Adjuvant Chemotherapy Following Pancreaticoduodenectomy in Elderly Patients With Pancreatic Cancer.

Anticancer Res 2019 Feb;39(2):1005-1012

Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan college of Medicine and Asan Medical Center, Seoul, Republic of Korea

Background/aim: The aim of this study was to investigate the relationship between age and long-term survival among patients who underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).

Patients And Methods: A total of 916 patients who underwent PD for curative resection of PDAC were included in this study. Patients were divided into younger (n=726, <70 years) and older (n=190, ≥70 years), and the overall survival (OS) between the two groups was compared.

Results: Median OS was significantly longer in the younger group (p<0.001). However, the survival advantage among younger patients was not significant when analyzing only patients who received adjuvant chemotherapy (p=0.548). Among patients who did not receive adjuvant chemotherapy, OS was significantly longer in the younger group (p=0.003). Among patients who received neither adjuvant chemotherapy nor treatment for recurrence, survival was not significantly different between the groups (p=0.629).

Conclusion: Adjuvant chemotherapy should be recommended, and additional treatment for recurrence is effective even among elderly who have not received adjuvant chemotherapy.
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http://dx.doi.org/10.21873/anticanres.13206DOI Listing
February 2019

The survival impact of surgical waiting time in patients with resectable pancreatic head cancer.

Ann Hepatobiliary Pancreat Surg 2018 Nov 27;22(4):405-411. Epub 2018 Nov 27.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Backgrounds/aims: After centralization policy, clinical outcomes have been improved in patients underwent pancreaticoduodenectomy for pancreatic cancer. However, centralization could exacerbate the prolongation of surgical waiting time. This study aims to investigate whether the shorter waiting time correlates with the better survival and to identify the major confounders that influence the association between those.

Methods: In this retrospective cohort study, a total 554 patients with pathologically confirmed pancreatic ductal adenocarcinoma were assessed the eligibility from 2014 through 2015. Patients with neoadjuvant chemotherapy, body-tail resection, total pancreatectomy and combined adjacent organ resection were excluded. All patients were divided into two groups by median waiting time, 21 days, defined as the date difference between initial imaging diagnosis and operation.

Results: Median overall survival did not differ between long and short waiting group (30.4 vs 24.8 months, =0.35; HR=0.84, 95% CI=0.58-1.21). The proportion of cancer stage shifting, the difference between clinical and pathologic staging, did not differ depending on waiting time group (=0.811 and 0.255, each of reviewers). Short waiting time was highly correlated with high initial clinical stage (Spearman correlation coefficients -0.201 (=0.006) and -0.100 (=0.175), each of reviewers).

Conclusions: Initial clinical stage had confounding effect on the association between waiting time and overall survival. Therefore, in evaluating centralization policy at the national level, evidence for maximum acceptable waiting time should be investigated in the near future with considering that surgical waiting time could be affected by initial clinical stage.
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http://dx.doi.org/10.14701/ahbps.2018.22.4.405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295371PMC
November 2018
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