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

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

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

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

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

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

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

Oncologic Benefits of Neoadjuvant Treatment versus Upfront Surgery in Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53-0.76) and resected patients (HR: 0.68, 95% CI = 0.60-0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.

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

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

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

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

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

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

Predicting prognosis and evaluating the benefits of adjuvant chemotherapy depending on the tumor location in intrahepatic cholangiocarcinoma: focusing on the involvement of below 2nd bile duct confluence.

Purpose: Intrahepatic cholangiocarcinoma (ICC) has various characteristics according to anatomical, histologic classifications, and its prognoses are different. This study aimed to compare oncologic outcomes according to tumor location (second bile duct confluence) and evaluate the effect of adjuvant chemotherapy. Methods: Clinical data of 318 patients who underwent curative resection for ICC was reviewed. Central type ICC (C-ICC) and peripheral type ICC (P-ICC) were defined when the tumor invades the intrahepatic secondary biliary confluence and when located more peripherally, respectively. Results: A larger tumor size, higher rate of elevated CA 19-9 level, vascular invasion, R1 resection, advanced T stage, and lymph node metastasis were found in C-ICC. C-ICC had poorer overall survival (median, 33 months vs. 58 months; P = 0.001), and the difference was more prominent in the early stage. C-ICC had a higher recurrence rate (68.7% vs. 55.1%, P = 0.014); otherwise, there was no difference in the recurrence patterns. There were no survival benefits of adjuvant chemotherapy in the entire cohort, but there were benefits in advanced stages (T3-4, N1 stage), especially in C-ICC. Conclusion: C-ICC has more aggressive tumor characteristics and poor survival compared to P-ICC. Adjuvant chemotherapy seems to have survival benefits in the advanced stages, especially in the central type.

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

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

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

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

Risk factors deteriorating severe exocrine pancreatic insufficiency measured by stool elastase after pancreatoduodenectomy and the risk factors for weight loss.

PURPOSE: The measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level. METHODS: Among patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to <100 µg/g postoperatively. Patients whose weight 12 months postoperatively was greater than that 3 months postoperatively were classified into the weight-recovery group. RESULTS: Of the 202 included patients, the deteriorated group had a higher incidence of preoperative SE level above 200 µg/g, benign pathology, and the presence of a clinically relevant postoperative pancreatic fistula than the maintained group. Patients who did not undergo weight recovery had a higher rate of history of adjuvant radiotherapy compared to the no-recovery group. CONCLUSION: The evaluation of EPI by measuring SE alone is not sufficient because it does not reflect the nutritional status of patients, and a comprehensive approach that considers other parameters is required for EPI management.

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

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

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

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

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

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

Management Algorithms for Pancreatic Cystic Neoplasms.

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

Clinical characteristics of patients with malignancy and long-term outcomes of surgical treatment of patients with choledochal cyst.

PURPOSE: There are few reports of postoperative long-term malignant risk or postoperative sequelae after surgery for choledochal cysts (CCs). This study aimed to analyze the clinical characteristics of patients with malignancy and the long-term results of operated CC. METHODS: The patients who underwent surgical treatments for CC between 2003 and 2020 at Seoul National University Hospital were enrolled. Clinicopathologic factors and pre-/postoperative computed tomography or magnetic resonance imaging were reviewed. RESULTS: Of the 153 patients, Todani classification Ic (36.6%), C-P type (43.8%) anomalous pancreaticobiliary duct union were the most common type respectively. Fourteen patients (9.2%) had biliary tract cancer and a comparison of patients with and without malignancy showed that the diameter of cyst was significantly lower in malignant patients and malignancy was observed to be significantly higher in P-C type. The incidence of long-term complications was 9.8%, and the median time interval was 30 months. The 2 most common complications were cholangitis and stricture (60.0%). There was one case of new cancer near the intrapancreatic remnant bile duct. CONCLUSION: Of the resected CCs, 9.2% had a combined malignancy on the biliary tracts. Long-term complications such as cholangitis, anastomotic stricture, and new cancers may occur. Therefore, continuous surveillance is required.

Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer.

BACKGROUND: Serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC. METHODS: Patients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: After excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 µg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 µg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0-II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent). CONCLUSION: Serum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC.

Limits of serum carcinoembryonic antigen and carbohydrate antigen 19-9 as the diagnosis of gallbladder cancer.

PURPOSE: Although serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC. METHODS: Between January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated. RESULTS: In terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively. CONCLUSION: Serum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.

Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells.

Hydrogen peroxide (H2O2), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of H2O2 causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the H2O2 concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric H2O2-responsive probe (NPDIN) composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous H2O2 in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of NPDIN in COX-2-overexpressing cancer cells. Collectively, our results demonstrated NPDIN as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (I554/I398) for H2O2 imaging and showed its promising biological applications in the future.