An Exosome-based Transcriptomic Signature for Noninvasive, Early Detection of Patients With Pancreatic Ductal Adenocarcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising worldwide, and most patients present with an unresectable disease at initial diagnosis. Measurement of carbohydrate antigen 19-9 (CA19-9) levels lacks adequate sensitivity and specificity for early detection; hence, there is an unmet need to develop alternate molecular diagnostic biomarkers for PDAC. Emerging evidence suggests that tumor-derived exosomal cargo, particularly micro RNAs (miRNAs), offer an attractive platform for the development of cancer-specific biomarkers. Herein, genomewide profiling in blood specimens was performed to develop an exosome-based transcriptomic signature for noninvasive and early detection of PDAC. METHODS: Small RNA sequencing was undertaken in a cohort of 44 patients with an early-stage PDAC and 57 nondisease controls. Using machine-learning algorithms, a panel of cell-free (cf) and exosomal (exo) miRNAs were prioritized that discriminated patients with PDAC from control subjects. Subsequently, the performance of the biomarkers was trained and validated in independent cohorts (n = 191) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. RESULTS: The sequencing analysis initially identified a panel of 30 overexpressed miRNAs in PDAC. Subsequently using qRT-PCR assays, the panel was reduced to 13 markers (5 cf- and 8 exo-miRNAs), which successfully identified patients with all stages of PDAC (area under the curve [AUC] = 0.98 training cohort; AUC = 0.93 validation cohort); but more importantly, was equally robust for the identification of early-stage PDAC (stages I and II; AUC = 0.93). Furthermore, this transcriptomic signature successfully identified CA19-9 negative cases (<37 U/mL; AUC = 0.96), when analyzed in combination with CA19-9 levels, significantly improved the overall diagnostic accuracy (AUC = 0.99 vs AUC = 0.86 for CA19-9 alone). CONCLUSIONS: In this study, an exosome-based liquid biopsy signature for the noninvasive and robust detection of patients with PDAC was developed.

Clinical impact of lactate on postoperative pancreatic fistula after pancreaticoduodenectomy: A single-center retrospective study of 1,043 patients.

BACKGROUND/OBJECTIVES: Several hemodynamic markers have been studied to predict postoperative complication which is a risk factor for poor quality of life and prognosis. The aim of this study was to determine whether postoperative lactate clearance could affect clinical outcome based on complications in one surgical patient group. METHODS: We retrospectively reviewed data from all patients who underwent pancreaticoduodenectomy (PD) at Samsung Medical Center from January 2015 to December 2019. Differences in baseline characteristics of patients, intraoperative outcome, and postoperative outcome were evaluated according to the presence or absence of clinically relevant postoperative pancreatic fistula (CR-POPF). RESULTS: Among a total of 1107 patients, 1043 patients were tested for arterial lactate levels immediately after surgery, and the day after surgery. Immediately postoperative hyperlactatemia (lactate ≥2.0 mmol/L) was not related to CR-POPF (P = 0.269). However, immediately postoperative hyperlactatemia with a negative lactic clearance on postoperative day (POD) 1 was related to CR-POPF (P = 0.003). In multivariate analyses, non-pancreatic cancer (hazard ratio (HR): 2.545, P < 0.001), soft pancreatic texture (HR: 1.884, P < 0.001), and postoperative hyperlactatemia with negative lactate clearance on POD 1 (HR: 1.805, P = 0.008) were independent risk factors for CR-POPF. CONCLUSIONS: Hyperlactatemia with negative lactate clearance after PD, one of the high-risk surgeries requiring postoperative ICU care, is a risk factor for CR-POPF. In case of immediately postoperative hyperlactatemia after PD, lactate clearance with serial lactate level follow-up can be used for achieving the hemodynamic goal to prevent CR-POPF.

Use of individualized 3D-printed models of pancreatic cancer to improve surgeons' anatomic understanding and surgical planning.

OBJECTIVES: Three-dimensional (3D) printing has been increasingly used to create accurate patient-specific 3D-printed models from medical imaging data. We aimed to evaluate the utility of 3D-printed models in the localization and understanding of pancreatic cancer for surgeons before pancreatic surgery. METHODS: Between March and September 2021, we prospectively enrolled 10 patients with suspected pancreatic cancer who were scheduled for surgery. We created an individualized 3D-printed model from preoperative CT images. Six surgeons (three staff and three residents) evaluated the CT images before and after the presentation of the 3D-printed model using a 7-item questionnaire (understanding of anatomy and pancreatic cancer [Q1-4], preoperative planning [Q5], and education for trainees or patients [Q6-7]) on a 5-point scale. Survey scores on Q1-5 before and after the presentation of the 3D-printed model were compared. Q6-7 assessed the 3D-printed model's effects on education compared to CT. Subgroup analysis was performed between staff and residents. RESULTS: After the 3D-printed model presentation, survey scores improved in all five questions (before 3.90 vs. after 4.56, p < 0.001), with a mean improvement of 0.57‒0.93. Staff and resident scores improved after a 3D-printed model presentation (p < 0.05), except for Q4 in the resident group. The mean difference was higher among the staff than among the residents (staff: 0.50‒0.97 vs. residents: 0.27‒0.90). The scores of the 3D-printed model for education were high (trainees: 4.47 vs. patients: 4.60) compared to CT. CONCLUSION: The 3D-printed model of pancreatic cancer improved surgeons' understanding of individual patients' pancreatic cancer and surgical planning. CLINICAL RELEVANCE STATEMENT: The 3D-printed model of pancreatic cancer can be created using a preoperative CT image, which not only assists surgeons in surgical planning but also serves as a valuable educational resource for patients and students. KEY POINTS: • A personalized 3D-printed pancreatic cancer model provides more intuitive information than CT, allowing surgeons to better visualize the tumor's location and relationship to neighboring organs. • In particular, the survey score was higher among staff who performed the surgery than among residents. • Individual patient pancreatic cancer models have the potential to be used for personalized patient education as well as resident education.

Propensity score matching analysis of perioperative outcomes including quality of life after multi-port vs. single port laparoscopic cholecystectomy: a nationwide prospective multicenter study in Korea.

INTRODUCTION: The usefulness of single-port laparoscopic cholecystectomy (SPLC) as compared to multi-port laparoscopic cholecystectomy (MPLC) remains controversial. Between SPLC and MPLC, we compared outcomes, especially subjective aspects, such as quality of life (QoL). MATERIAL AND METHODS: This multi-center study, involving 20 institutions from 2016 to 2017, enrolled 2507 patients who underwent laparoscopic cholecystectomy. Various perioperative outcomes, pain assessed by the numeric rating scale (NRS) score, and QoL evaluated by the gastrointestinal QoL index (GIQLI) questionnaire, were compared between the two procedures. We generated balanced groups after propensity score matching (PSM) using preoperative factors that influence the decision to perform MPLC or SPLC. RESULTS: MPLC and SPLC were performed in 2176 and 331 patients, respectively. Nine hundred and twelve and 329 patients, respectively, were selected from the two groups by PSM. Operation time was longer and surgical difficulty was lower in SPLC. There were no significant differences in most outcomes, including biliary complications. Significant superiority of SPLC over MPLC was shorter hospitalization, lower NRS score, and favorable GIQLI. CONCLUSIONS: From nationwide prospective data, SPLC showed outcomes comparable to MPLC. In SPLC, morbidity was not high and postoperative QoL was favorable. In the future, more implementations and studies are needed to ensure the safety and feasibility of SPLC.

Transcriptomic Profiling Identifies an Exosomal microRNA Signature for Predicting Recurrence Following Surgery in Patients With Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We performed genome-wide expression profiling to develop an exosomal miRNA panel for predicting recurrence following surgery in patients with PDAC. SUMMARY OF BACKGROUND DATA: Pretreatment risk stratification is essential for offering individualized treatments to patients with PDAC, but predicting recurrence following surgery remains clinically challenging. METHODS: We analyzed 210 plasma and serum specimens from 4 cohorts of PDAC patients. Using a discovery cohort (n = 25), we performed genome-wide sequencing to identify candidate exosomal miRNAs (exo-miRNAs). Subsequently, we trained and validated the predictive performance of the exo-miRNAs in two clinical cohorts (training cohort: n = 82, validation cohort: n = 57) without neoadjuvant therapy (NAT), followed by a post-NAT clinical cohort (n = 46) as additional validation. RESULTS: We performed exo-miRNA expression profiling in plasma specimens obtained before any treatment in a discovery cohort. Subsequently we optimized and trained a 6-exo-miRNA risk-prediction model, which robustly discriminated patients with recurrence [area under the curve (AUC): 0.81, 95% confidence interval (CI): 0.70-0.89] and relapse-free survival (RFS, P < 0.01) in the training cohort. The identified exo-miRNA panel was successfully validated in an independent validation cohort (AUC: 0.78, 95% CI: 0.65- 0.88, RFS: P < 0.01), where it exhibited comparable performance in the post-NAT cohort (AUC: 0.72, 95% CI: 0.57-0.85, RFS: P < 0.01) and emerged as an independent predictor for RFS (hazard ratio: 2.84, 95% CI: 1.30-6.20). CONCLUSIONS: We identified a novel, noninvasive exo-miRNA signature that robustly predicts recurrence following surgery in patients with PDAC; highlighting its potential clinical impact for optimized patient selection and improved individualized treatment strategies.

Utility of Diffusion-Weighted MRI for Detection of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND. Overlapping imaging findings between local tumor recurrence and postsurgical fibrosis represent a major clinical challenge after pancreatic ductal adeno-carcinoma (PDAC) resection. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of MRI with and without DWI for differentiating locally recurrent tumor and postsurgical fibrosis after PDAC resection. METHODS. This retrospective study included 66 patients (35 men, 31 women; mean age, 60.5 years) who underwent PDAC resection between January 2009 and March 2016, postoperative surveillance CT showing a soft-tissue lesion at the operative site or at the site of peripancreatic vessels, and subsequent MRI with DWI for further evaluation. CT at least 6 months after MRI served as the reference standard, with increase in size of the soft tissue by 5 mm or more differentiating locally recurrent tumor (n = 26) and postsurgical fibrosis (n = 40). Two observers in consensus evaluated MRI characteristics of the soft-tissue lesions. Two additional observers independently reviewed MRI examinations in two separate sessions (conventional MRI alone vs MRI with DWI), recording likelihood of recurrent tumor using a 1-5 scale. ROC analysis was performed, considering scores of 4 or 5 as positive. RESULTS. Subjective diffusion restriction was more common in locally recurrent tumor than postsurgical fibrosis (88.5% vs 25.0%, p = .01). Median ADC was lower for locally recurrent tumor than postsurgical fibrosis (1.3 vs 1.7 × 10-3 mm2/s, p < .001). For both observers, MRI with DWI in comparison with conventional MRI alone showed higher AUC for diagnosis of locally recurrent tumor (observer 1: 0.805 vs 0.707, p = .048; observer 2: 0.898 vs 0.637, p < .001) and higher sensitivity (observer 1: 88.5% vs 61.5%, p = .008; observer 2: 84.6% vs 42.3%, p = .001) but no difference in specificity (observer 1: 72.5% vs 80.0%, p = .08; observer 2, 95.0% vs 85.0%, p = .10). Interobserver agreement was moderate for conventional MRI (κ = 0.41) and good for conventional MRI with DWI (κ = 0.62). CONCLUSION. The addition of DWI to conventional MRI improves the differentiation of locally recurrent tumor and postsurgical fibrosis after PDAC resection, primarily because of improved sensitivity for recurrence. CLINICAL IMPACT. The findings indicate a potential role for MRI with DWI in surveillance protocols after PDAC resection.

Surgical outcomes and prognostic factors of distal common bile duct adenocarcinoma: chronological analysis in a single high-volume institutional experience.

BACKGROUND: Distal common bile duct (dCBD) cancer is typical indication for pancreaticoduodenectomy (PD). We aimed to retrospectively evaluate surgical outcomes and investigate prognostic factors of dCBD adenocarcinoma for which PD was performed at a single institution. METHODS: We searched consecutive cases of dCBD adenocarcinoma undergone PD at Samsung Medical Center from 1995 to 2018. Cases with distant metastasis or palliative intent were excluded. The year in which the survival rate was dramatically improved was identified and entire years were divided into two periods for comparison. To balance between the two periods, we conducted propensity score matching (PSM) analysis using age, sex, body mass index (BMI), and American Society of Anesthesiologist score. RESULTS: Total of 804 cases were enrolled in this study. The entire period was divided into early period of 18 years and recent period of 6 years. The early and late period included 466 and 338 patients, respectively. As a result of PSM, balanced 316 patients were selected from each of the two periods. Significant improvements in surgical outcomes were identified, including shorter operation time, fewer blood loss, shorter hospitalization, and favorable overall survival. As results of multivariable analysis of independent risk factors for overall survival, older age and advanced N stage were identified, as expected. It was distinct that aggressive surgery and advanced tumor state in the early period and a lower BMI in the late period negatively affected the survival, respectively. CONCLUSIONS: Surgical outcomes of dCBD cancer underwent PD was improved. There were few modifiable factors to improve survival and continuous further study is needed to detect dCBD cancer in the early stages.

Optimal stapler cartridge selection to reduce post-operative pancreatic fistula according to the pancreatic characteristics in stapler closure distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is associated with potentially fatal complications, but there is lack of data on relationship between pancreas thickness, and stapler size and the POPF rate. This study aimed to suggest optimal stapler that reduces POPF rate according to the pancreas thickness. METHODS: This retrospective cohort study was conducted in two tertiary high-volume pancreas centers. 599 patients who underwent distal pancreatectomy were assessed for stump reinforcement methods, pathology findings, pancreas thickness, and cartridge used. The cartridges were grouped as I, II, III according to the closed height ≤1.5 mm, 1.8 mm, and ≥2.0 mm, respectively. RESULTS: The POPF rate increased according to the thickness. The stapler Groups I, II, and III had an overall POPF rate of 66.4% vs. 61.7% vs. 57.8%, but Group II stapler cartridge showed a significant reduction in the POPF rate than other cartridges in pancreas with thickness <13 mm (53.5% vs. 21.7% vs. 36.0%, p = 0.031). There was no significant difference between the POPF rate according to stapler groups when the pancreas was thicker than 13 mm. CONCLUSION: Thickness is the strongest risk factor in predicting POPF. Use of Group II stapler cartridge for pancreas with a thickness of <13 mm can help reduce POPF.

Effects of Pancreatic Enzyme Replacement Therapy on Body Weight and Nutritional Assessments After Pancreatoduodenectomy in a Randomized Trial.

BACKGROUND & AIMS: We studied the effects of pancreatic enzyme replacement therapy (PERT) on body weight, nutritional status, and quality of life (QoL) in patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. METHODS: We performed a randomized, double-blind trial of 304 patients who underwent pancreatoduodenectomy at 7 tertiary referral hospitals in South Korea. Patients with fecal levels of elastase of 200 µg/g or less, before and after surgery, were assigned randomly to groups that received PERT (a single capsule of 40,000 IU pancreatin, Norzyme (40,000 IU, Pankreatan; Nordmark Arzneimittel GmbH & Co, Uetersen, Germany), 3 times each day during meals for 3 months; n = 151) or placebo (n = 153). Protocol completion was defined as taking more than two thirds of the total dose without taking other digestive enzymes; the protocol was completed by 71 patients in the PERT group and 93 patients in the placebo group. Patients underwent a physical examination, oral glucose tolerance tests, and blood tests at baseline and at month 3 of the study period. The primary end point was change in body weight. Secondary end points were changes in bowel habits, nutritional parameters, and QoL. RESULTS: In the per-protocol analysis, 3 months after the study began, patients in the PERT group gained a mean of 1.09 kg in weight and patients in the placebo group lost a mean of 2.28 kg (difference between groups, 3.37 kg; P < .001). However, no difference in body weight was observed between groups in the intent-to-treat analysis. Three months after the study began, the mean serum levels of prealbumin increased by 10.9 mg/dL in the PERT group and increased by 7.8 mg/dL in the placebo group (P = .002). Poor compliance to PERT was a significant risk factor for weight loss (P < .001). There was no significant difference in QoL scores between groups. CONCLUSIONS: In the intent-to-treat analysis of data from a randomized trial, we found no significant effect of PERT on mean body weights of patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. However, with active education and monitoring, PERT could increase body weight and nutritional parameters. ClinicalTrials.gov no: NCT02127021.

Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma.

BACKGROUND: The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). METHODS: From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. RESULTS: The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (p = 0.002), nodal involvement (p < 0.001), poor differentiation (p < 0.001), perineural and lymphovascular invasion (p < 0.001), and pancreatobiliary or mixed subtype (p < 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (p = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (p < 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; p < 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. CONCLUSION: FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Laparoscopic versus open distal pancreatectomy for nonfunctioning pancreatic neuroendocrine tumors: a large single-center study.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) account for 1-2% of all pancreatic neoplasms. Nonfunctioning PNETs (NF-PNETs) account for 60-90% of all PNETs. Laparoscopic distal pancreatectomy (LDP) is becoming the treatment of choice for benign lesions in the body and tail of the pancreas. However, LDP has not yet been widely accepted as the gold standard for NF-PNETs. The purpose of this study is to evaluate the clinical and oncologic outcomes after laparoscopic versus open distal pancreatectomy (ODP) for NF-PNETs. METHODS: Between April 1995 and September 2016, 94 patients with NF-PNETs underwent open or laparoscopic distal pancreatectomy at Samsung Medical Center. Patients were divided into two groups: those who underwent LDP and those who underwent ODP. Both groups were compared in terms of clinical and oncologic variables. RESULTS: LDP patients had a significantly shorter hospital stay compared with ODP patients, amounting to a mean difference of 2 days (p < 0.001). Overall complication rates did not differ significantly between the ODP and LDP groups (p = 0.379). The 3-year overall survival rates in the ODP and LDP groups were 93.7 and 100%, respectively (p = 0.069). CONCLUSIONS: In this study, LDP for NF-PNETs had similar oncologic outcomes compared with ODP. In addition, LDP was associated with a shorter hospital stay compared with ODP. Therefore, LDP is a safe and effective procedure for patients with NF-PNETs. A multicenter study and a randomized controlled trial are needed to better assess the clinical and oncologic outcomes.

Effects of Rowachol on prevention of postcholecystectomy pain after laparoscopic cholecystectomy: prospective multicenter randomized controlled trial.

BACKGROUND: Postcholecystectomy pain (PCP) is characterized by abdominal pain after cholecystectomy. However, prevention of PCP is not well known yet. The purpose of this study was to determine whether Rowachol might be useful in preventing PCP. METHODS: Between May 2013 and January 2014, a total of 138 patients with gallbladder disease who were scheduled to undergo laparoscopic cholecystectomy were randomly assigned to orally receive 100 mg Rowachol or placebo three times daily for 3 months after surgery. Abdominal pain was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: Incidence of PCP in the placebo group (n = 9, 14.3%) was higher than that in the Rowachol group (n = 3, 4.7%) with statistically marginal significance (P = 0.08). Risk factor analysis implicated PCP with increased difficulty in performing LC, more frequent pathology with acute cholecystitis, and absence of postoperative Rowachol treatment. Multivariate analysis revealed that greater difficulty of laparoscopic cholecystectomy (HR = 5.78, 95% CI 1.36-24.40, P < 0.05), and absence of postoperative Rowachol treatment (HR = 2.54, 95% CI 1.10-10.39, P < 0.05) were independent risk factors for development of PCP. CONCLUSION: Rowachol might be beneficial for prevention of PCP after laparoscopic cholecystectomy.

Clinicopathologic analysis of gastrointestinal stromal tumors in duodenum and small intestine.

BACKGROUND: The prognosis about duodenal GISTs is debatable. The purpose of this study is to compare the characteristics and the prognostic factors in patients with gastrointestinal stromal tumor (GIST) located in the duodenum with those located in the small intestine. METHODS: One hundred-one patients with GIST located in the duodenum (n = 40), or small intestine (n = 61) underwent resection between 1996 and 2010. We analyzed clinicopathologic features, surgical outcomes, and prognostic factors. RESULTS: Five-year survival rate in patients with GIST located in the duodenum and small intestine were 66.6 and 80.8%, respectively (p = 0.018). After survival analysis, high mitotic count and tumor rupture were identified as independent adverse prognostic factors. Advanced T stage and absence of adjuvant imatinib treatment were adverse prognostic factors with marginal statistical significance. The rate of progressive disease was significantly higher in patients with duodenal GISTs (36.8%) than in those with small intestinal GIST (29.6%) (p = 0.024). CONCLUSIONS: The clinicopathologic findings of duodenal GIST differ from those of small intestinal GIST. Patients with duodenal GIST have a worse prognosis than those with small intestinal GIST. Aggressive treatment including surgical resection should be considered for duodenal GIST, even if the risk is relatively low.

Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer.

BACKGROUND: Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer (BDC), maintenance of patency is still unsatisfactory. We tried to assess the effectiveness and safety of external beam radiotherapy (EBRT) for prolonging stent patency in patients having uncovered metallic stents. METHOD: We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT (RT group) and 32 did not (non-RT group). RESULTS: No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group (140.7+/-51.3 vs 136.4+/-34.9 days, P=0.94), the difference was not statistically significant. There were a lower rate of stent occlusion (27.8% vs 50.0% of patients, P=0.12) and a longer overall survival (420.1+/-73.2 vs 269.1+/-41.7 days, P=0.11) in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ (55.6% vs 53.1% of patients, P=0.91). There was no serious adverse reaction in both groups (P=0.99). CONCLUSIONS: EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials with refined protocols for better efficacy are expected.

Clinicopathological analysis and prognosis of extrahepatic bile duct cancer with a microscopic positive ductal margin.

BACKGROUND: The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. METHODS: Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. RESULTS: One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). CONCLUSIONS: The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important.

Twenty-one years of experience with resected solid pseudopapillary neoplasm: a retrospective single-institutional cohort study.

BACKGROUND: Although the incidence of solid pseudopapillary neoplasm (SPN) is <2% of the incidence of pancreatic tumor, the prevalence seems to be increasing. SPNs are mostly benign. However, they also show malignant features. This study aimed to identify the clinical outcomes of patients who underwent surgery for SPN at a single center. METHODS: Data on 217 patients with SPN who underwent surgery in Samsung Medical Center between 2000 and 2020 were retrospectively analyzed. RESULTS: Herein, the mean age of the 217 patients was 40.0 ± 12.6 years, with a female predominance (80.6%). Most patients had no comorbidity. The mean tumor size was 4.4 ± 3.1 cm. The tumor was located at the pancreatic head in 36 patients (16.6%), the body of the pancreas in 69 patients (31.8%), and the pancreatic tail in 96 patients (44.2%). Of note, 35 patients (16.1%) underwent pancreaticoduodenectomies, 148 patients (68.2%) had distal pancreatectomies, and the other patients had subtotal /total pancreatectomy (9.7%) or enucleation/mass excision (6.0%). No patient had lymph node (LN) metastasis. Moreover, 6 patients (2.8%) had a recurrence in the liver or regional LNs. The 5-year recurrence-free survival rate was 96.8%. The only factor affecting recurrence was tumor size (P = .007). CONCLUSION: Because SPN predominates in relatively young women, patients often hesitate to undergo surgery. Nevertheless, as size is the prognostic factor, early resection is recommended for a better prognosis in the case of surgically feasible, young age, and healthy patients.

Fate of small remnant pancreatic tail in splenic hilum after laparoscopic spleen preserving distal pancreatectomy: a retrospective study.

Purpose: When performing laparoscopic spleen-preserving distal pancreatectomy (LSPDP), sometimes, anatomically challenging patients are encountered, where the pancreatic tail is deep in the splenic hilum. The purpose of this study was to discuss the experience with the surgical technique of leaving the deep pancreatic tail of the splenic hilum in these patients. Methods: Eleven patients who underwent LSPDP with remnant pancreatic tails between November 2019 and August 2021 at Samsung Medical Center in Seoul, Korea were included in the study. Their short-term postoperative outcomes were analyzed retrospectively. Results: The mean operative time was 168.6 ± 26.0 minutes, the estimated blood loss was 172.7 ± 95.8 mL, and the postoperative length of stay was 6.1 ± 1.0 days. All 11 lesions were in the body or tail of the pancreas and included 2 intraductal papillary mucinous neoplasms, 6 neuroendocrine tumors, 2 cystic neoplasms, and 1 patient with chronic pancreatitis. In 10 of the 11 patients, only the pancreatic tail was left inside the distal portion of the splenic hilum of the branching splenic vessel, and there was a collection of intraabdominal fluid, which was naturally resolved. One patient with a remnant pancreatic tail above the hilar vessels was readmitted due to a postoperative pancreatic fistula with fever and underwent internal drainage. Conclusion: In spleen preservation, leaving a small pancreatic tail inside the splenic hilum is feasible and more beneficial to the patient than performing splenectomy in anatomically challenging patients.

Pancreatic Metastasectomy for Secondary Malignancy of the Pancreas: A Single-institution Experience.

BACKGROUND/AIM: Metastasis to the pancreas is rare, and the benefit of resection for secondary pancreatic cancer is poorly defined. Furthermore, there are no guidelines for pancreatic metastasectomy in such patients. The purpose of this study was to discuss our experience with the operative management of secondary pancreatic cancer. PATIENTS AND METHODS: This retrospective study included 76 patients who underwent pancreatic metastasectomy for secondary pancreatic cancer between January 2000 and December 2020 at Samsung Medical Center, Seoul, Republic of Korea. RESULTS: Among the study subjects, 44 underwent distal pancreatectomy, 21 pancreaticoduodenectomy, 5 total pancreatectomy, and 6 enucleation or wedge resection for metastasis. The overall survival (OS) and recurrence-free survival (RFS) were higher in the patients with RCC than in patients with other malignancies (p=0.004 and p=0.051, respectively). Statistically significant differences were not observed in OS and RFS between patients with right RCC (rRCC) or left RCC (lRCC; p=0.523 and p=0.586, respectively). CONCLUSION: Pancreatic metastasectomy may offer promising outcomes regarding curative intent in instances of secondary pancreatic metastasis, particularly in the context of RCC. However, regarding the side of primary RCC, no statistically significant differences were found in OS and RFS between rRCC and lRCC.

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

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