Publications by authors named "Dae Wook Hwang"

145 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

The impact of preoperative EUS-FNA for distal resectable pancreatic cancer: Is it really effective enough to take risks?

Surg Endosc 2021 Jul 12. Epub 2021 Jul 12.

Division of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Background And Aims: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently used for the preoperative histologic diagnosis of pancreatic cancer. However, debate continues regarding the clinical merits of preoperative EUS-FNA for the management of resectable pancreatic cancer. We aimed to evaluate the benefits and safety of preoperative EUS-FNA for resectable distal pancreatic cancer.

Methods: The medical records of 304 consecutive patients with suspected distal pancreatic cancer who underwent EUS-FNA were retrospectively reviewed to evaluate the clinical benefits of preoperative EUS-FNA. We also reviewed the medical records of 528 patients diagnosed with distal pancreatic cancer who underwent distal pancreatectomy with or without EUS-FNA. The recurrence rates and cancer-free survival periods of patients who did or did not undergo preoperative EUS-FNA were compared.

Results: The diagnostic accuracy of preoperative EUS-FNA was high (sensitivity, 87.5%; specificity, 100%; positive predictive value 100%; accuracy, 90.7%; negative predictive value, 73.8%). Among patients, 26.7% (79/304) avoided surgery based on the preoperative EUS-FNA findings. Of the 528 patients who underwent distal pancreatectomy, 193 patients received EUS-FNA and 335 did not. During follow-up (median 21.7 months), the recurrence rate was similar in the two groups (EUS-FNA, 72.7%; non-EUS-FNA, 75%; P = 0.58). The median cancer-free survival was also similar (P = 0.58); however, gastric wall recurrence was only encountered in the patients with EUS-FNA (n = 2).

Conclusion: Preoperative EUS-FNA is not associated with increased risks of cancer-specific or overall survival. However, clinicians must consider the potential risks of needle tract seeding, and care should be taken when selecting patients.
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http://dx.doi.org/10.1007/s00464-021-08627-3DOI Listing
July 2021

Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

Ann Surg Oncol 2021 May 9. Epub 2021 May 9.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea.

Background: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs.

Methods: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis.

Results: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location.

Conclusion: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.
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http://dx.doi.org/10.1245/s10434-021-10092-0DOI Listing
May 2021

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Database: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP).

Gut Liver 2021 May 7. Epub 2021 May 7.

Department of Statistics and Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Korea.

Background/aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database.

Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated.

Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively.

Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.
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http://dx.doi.org/10.5009/gnl20306DOI Listing
May 2021

Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

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

Biliary tract cancers (BTCs) are a group of aggressive malignancies that arise from the bile duct and gallbladder. BTCs include intrahepatic cholangiocarcinoma (IH-CCA), extrahepatic cholangiocarcinoma (EH-CCA), and gallbladder cancer (GBCA). BTCs are highly heterogeneous cancers in terms of anatomical, clinical, and pathological characteristics. Until recently, the treatment of resectable BTC, including surgery, adjuvant chemotherapy, and radiation therapy, has largely been based on institutional practice guidelines and evidence from small retrospective studies. Recently, several large randomized prospective trials have been published, and there are ongoing randomized trials for resectable BTC. In this article, we review prior and recently updated evidence regarding surgery, adjuvant and neoadjuvant chemotherapy, and adjuvant radiation therapy for patients with resectable BTC.
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http://dx.doi.org/10.3390/cancers13071647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037230PMC
April 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

Effectiveness of early endoscopic ultrasound-guided drainage for postoperative fluid collection.

Surg Endosc 2021 Jan 28. Epub 2021 Jan 28.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea.

Background: Postoperative abdominal fluid collections (PAFCs) are a potentially fatal complication of pancreatobiliary surgery. Endoscopic ultrasound (EUS)-guided drainage has recently been shown to be effective in treating PAFCs of more than 4 weeks old. Little is currently known, however, regarding the EUS-guided drainage of PAFCs of less than 4 weeks. This study assessed the efficacy and safety of the early drainage (< 4 weeks) of PAFCs via EUS guidance.

Methods: The data of patients who had undergone EUS-guided PAFC drainage between July 2008 and January 2018 were retrospectively analyzed. Data of EUS-guided PAFC drainage were obtained from prospectively collected EUS database of our institute and reviewed of patients' clinical parameters based on electrical medical record.

Results: A total of 48 patients who had undergone EUS-guided PAFC drainage within 4 weeks of pancreatobiliary surgery were enrolled. The indications of procedure included abdominal pain (n = 27), fever (n = 18), leukocytosis (n = 2), and increased size of PAFC during external tube drainage (n = 1). Technical success was achieved in all cases, and the clinical success rate was 95.8% (46/48). Four patients underwent secondary procedures. The median period from surgery to EUS-guide drainage was 14 days (Interquartile range [IQR] 10-16), and median time to resolution was 23.5 days (IQR 8.5-33.8). Adverse events occurred in two cases that were developed intracystic bleeding and were successfully resolved by arterial coil embolization.

Conclusions: Early EUS-guided drainage is a technically feasible, effective, and safe method in patients who have developing PAFCs within 4 weeks of pancreatobiliary surgery.
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http://dx.doi.org/10.1007/s00464-020-08247-3DOI Listing
January 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

Predictors of early recurrence following a curative resection in patients with a carcinoma of the ampulla of Vater.

Ann Surg Treat Res 2020 Nov 28;99(5):259-267. Epub 2020 Oct 28.

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

Purpose: Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%-50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection.

Methods: The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection.

Results: There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30-94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year.

Conclusion: An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.
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http://dx.doi.org/10.4174/astr.2020.99.5.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606130PMC
November 2020

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

Risk factors for recurrence in pancreatic neuroendocrine tumor and size as a surrogate in determining the treatment strategy: a Korean nationwide study.

Neuroendocrinology 2020 Oct 1. Epub 2020 Oct 1.

Introduction: The prognostic factors of PNET are unclear, and the treatment guidelines are insufficient. This study aimed to suggest a treatment algorithm for pancreatic neuroendocrine tumor (PNET) based on risk factors for recurrence in a large cohort.

Methods: Data of 918 patients who underwent curative intent surgery for PNET were collected from 14 tertiary centers. Risk factors for recurrence and survival analyses were performed.

Results: The 5-year disease-free survival (DFS) rate was 86.5%. Risk factors for recurrence included margin status (R1, hazard ratio [HR] 2.438; R2, HR 3.721), 2010 WHO grade (G2, HR 3.864; G3, HR 7.352), and N category (N1, HR 2.273). Size of 2 cm was significant in the univariate analysis (HR 8.511) but not in the multivariate analysis (p=0.407). Tumor size was not a risk factor for recurrence, but strongly reflected 2010 WHO grade and lymph node (LN) status. Tumors ≤2 cm had lower 2010 WHO grade, less LN metastasis (p<0.001), and significantly longer 5-year DFS (77.9% vs. 98.2%, p<0.001) than tumors >2 cm. The clinicopathologic features of tumors <1 cm and 1-2 cm were similar. However, the LN metastasis rate was 10.3% in 1-2 cm sized tumors, and recurrence occurred in 3.0%. Tumors <1 cm in size did not have any LN metastasis or recurrence.

Discussion/conclusion: Radical surgery is needed in suspected LN metastasis or G3 PNET or tumors >2 cm. Surveillance for <1 cm PNETs should be sufficient. Tumors sized 1-2 cm require limited surgery with LN resection, but should be converted to radical surgery in cases of doubtful margins or LN metastasis.
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http://dx.doi.org/10.1159/000511875DOI 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

FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma.

Ther Adv Med Oncol 2020 16;12:1758835920953294. Epub 2020 Sep 16.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, South Korea.

Background: Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC.

Methods: This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status.

Results: With median follow-up duration of 40.3 months [95% confidence interval (CI), 36.7-43.8] in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5-11.7) and 18.1 (95% CI, 16.0-20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3-66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5-37.9%). PFS and OS did not differ between BRPC and LAPC groups [median PFS, 11.1 months (95% CI, 8.8-13.5) 10.1 months (95% CI, 8.4-11.8),  = 0.47; median OS, 18.4 months (95% CI, 16.1-20.8) 17.1 months (95% CI, 13.2-20.9),  = 0.50]. Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS.

Conclusion: FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.
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http://dx.doi.org/10.1177/1758835920953294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498966PMC
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

Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer.

Cancer Res Treat 2021 Jan 31;53(1):162-171. Epub 2020 Aug 31.

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

Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.

Materials And Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.

Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.

Conclusion: The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.
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http://dx.doi.org/10.4143/crt.2020.704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812013PMC
January 2021

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

Clinical features and outcomes of endovascular treatment of latent pseudoaneurysmal bleeding after pancreaticoduodenectomy.

ANZ J Surg 2020 12 6;90(12):E148-E153. Epub 2020 Aug 6.

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

Background: The endovascular treatment is the first-line therapy for late massive arterial haemorrhage after pancreaticoduodenectomy (PD). This study aimed to evaluate the clinical features and outcomes of patients who experienced pseudoaneurysm (PA) bleeding after PD and treated with transcatheter arterial embolization (TAE) and stent-graft placement (SGP).

Methods: A total of 37 patients (TAE = 16, stent graft = 16, both = 5) had an endovascular treatment due to hepatic artery PA bleeding after PD at our institution from January 2008 to December 2018.

Results: There were 35 men and two women with a mean age of 62 years (range 45-82 years). The latency of bleeding ranged from postoperative days 3 to 46 (median day 21). The most common site of bleeding was gastroduodenal artery stump (n = 22). In TAE group (n = 16), the technical success rate was 100% and the clinical success rate was 87.5%. In SGP group (n = 16), the technical and clinical success rates were 100% and 93.8%. Five patients underwent SGP and TAE simultaneously; TAE was performed to prevent endoleak. A total of three patients experienced hepatic ischaemia (TAE = 2, SGP = 1). However, there was no statistically significant difference of hepatic ischaemia occurrence between the two groups P = 0.55).

Conclusions: In patients with suspected PA, urgent angiography should be considered immediately for diagnosis and treatment. The SGP can be performed first if it is technically feasible. However, TAE is also a safe and effective treatment in patients with intact portal flow, as well as those with preserved collateral pathways after hepatobiliary surgery.
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http://dx.doi.org/10.1111/ans.16184DOI Listing
December 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

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas.

J Pathol Transl Med 2020 Sep 21;54(5):387-395. Epub 2020 Jul 21.

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

Background: Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis.

Methods: We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points.

Results: A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p<.001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively.

Conclusions: The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.
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http://dx.doi.org/10.4132/jptm.2020.06.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483027PMC
September 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

Large tumor size, lymphovascular invasion, and synchronous metastasis are associated with the recurrence of solid pseudopapillary neoplasms of the pancreas.

HPB (Oxford) 2021 Feb 9;23(2):220-230. Epub 2020 Jul 9.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood.

Methods: To evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared.

Results: Fifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P < 0.001), and synchronous metastasis (P < 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P < 0.01), and lymphovascular invasion (P < 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence.

Conclusion: Lymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.
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http://dx.doi.org/10.1016/j.hpb.2020.05.015DOI Listing
February 2021

Prognostic implication of high grade biliary intraepithelial neoplasia in bile duct resection margins in patients with resected perihilar cholangiocarcinoma.

J Hepatobiliary Pancreat Sci 2020 Sep 16;27(9):604-613. Epub 2020 Aug 16.

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

Background: In surgery for perihilar cholangiocarcinoma (PHCC), it is still controversial as to whether additional resection of the bile duct is needed on high grade (HG) biliary intraepithelial neoplasia (BilIN) margin.

Methods: Patients who underwent surgery for PHCC with curative intent between 2001 and 2015 were stratified by resection margin, and were analyzed comparing the clinical outcomes.

Results: Of the 306 study participants, 217 patients had negative margins (R0), 18 patients had HG BilIN, and 71 patients had positive margins (R1). The median overall survival was 36.0 months in the R0 group, 41.0 months in the HG BilIN group, and 25.0 months in the R1 group while overall survival rates at 5 years were 34.5% in the R0 group, 44.4% in the HG BilIN group, and 21.0% in the R1 group. The median disease-free survival was 15.0 months in the R0 group, 16.5 months in the HG BilIN group, and 12.0 months in the R1 group.

Conclusions: Although the HG BilIN group had neoplasia with malignant potential, survival and recurrence outcomes were comparable to those of the R0 group, which suggests that no additional resection is needed when the maximal bile duct margin in PHCC surgery contains HG BilIN.
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http://dx.doi.org/10.1002/jhbp.800DOI Listing
September 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

Human equilibrative nucleoside transporter-1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression; do they have survival impact to pancreatic cancer?

Ann Hepatobiliary Pancreat Surg 2020 May;24(2):127-136

Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Backgrounds/aims: Gemcitabine is still one of adjuvant options in chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). Integral membrane transporter protein and intracellular enzymes including human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), ribonucleotide reductase (RR) M1, and M2 are known as important factors for chemosensitivity of gemcitabine. We aimed to investigate the correlation between these key molecules and 5-year actual survival in PDAC patients.

Methods: The expression of intratumoral hENT1, dCK, RRM1, and RRM2 was assessed immunohistochemically in 160 PDAC patients underwent surgical resection. Association between clininopathologic factors, immunohistochemical results, and overall survival were analyzed.

Results: Adjuvant chemotherapy including concurrent chemoradiotherapy was not associated with overall survival (HR, 0.92; 95% CI, 0.65-1.31; =0.658). High hENT1 expression group did not show statistical survival difference, compared with all others (HR, 1.16; 95% CI, 0.82-1.65, =0.396). Gemcitabine therapy and high hENT1 group was compared with all other patients, and no difference in overall survival was identified (HR, 0.99; 95% CI, 0.68-1.42; =0.940). And, gemcitabine therapy and high hENT1 group did not differ statistically from gemcitabine therapy and low hENT1 expression (HR, 0.92; 95% CI, 0.55-1.56; =0.764). The intensity of dCK, RRM1, and RRM2 expression was not associated with overall survival (=0.413, =0.138 and =0.061) in univariate analysis.

Conclusions: The expression of hENT1, dCK, RRM1 and RRM2 may not be associated with overall survival for patients with pancreatic cancer on gemcitabine adjuvant therapy. These proteins and other factors that may interact with or confound these results should be investigated in the near future.
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http://dx.doi.org/10.14701/ahbps.2020.24.2.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271117PMC
May 2020

Neoadjuvant modified FOLFIRINOX followed by postoperative gemcitabine in borderline resectable pancreatic adenocarcinoma: a Phase 2 study for clinical and biomarker analysis.

Br J Cancer 2020 08 20;123(3):362-368. Epub 2020 May 20.

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

Background: Patients with borderline resectable pancreatic cancer (BRPC) have poor prognosis with upfront surgery.

Methods: This was a single-arm Phase 2 trial for clinical and biomarker analysis. The primary endpoint is 1-year progression-free survival (PFS) rate. Patients received 8 cycles of neoadjuvant modified (m) FOLFIRINOX. Up to 6 cycles of gemcitabine were given for patients who underwent surgery. Plasma immune cell subsets were measured for analysing correlations with overall survival (OS).

Results: Between May 2016 and March 2018, 44 chemotherapy- and radiotherapy-naïve patients with BRPC were included. With neoadjuvant mFOLFIRINOX, the objective response rate was 34.1%, and curative-intent surgery was done in 27 (61.4%) patients. With a median follow-up duration of 20.6 months (95% confidence interval [CI], 19.7-21.6 months), the median PFS and OS were 12.2 months (95% CI, 8.9-15.5 months) and 24.7 months (95% CI, 12.6-36.9), respectively. The 1-year PFS rate was 52.3% (95% CI, 37.6-67.0%). Higher CD14 monocyte (quartile 4 vs 1-3) and lower CD69 γδ T cell (γδ TCR/CD69) levels (quartiles 1-3 vs 4) were significantly associated with poor OS (p = 0.045 and p = 0.043, respectively).

Conclusions: Neoadjuvant mFOLFIRINOX followed by postoperative gemcitabine were feasible and effective in BRPC patients. Monocyte and γδ T cells may have prognostic implications for patients with pancreatic cancer. ClinicalTrials.gov identifier: NCT02749136.
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http://dx.doi.org/10.1038/s41416-020-0867-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403346PMC
August 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
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