Machine-Learning Model for the Prediction of Hypoxaemia during Endoscopic Retrograde Cholangiopancreatography under Monitored Anaesthesia Care

Purpose@#Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. @*Materials and Methods@#We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). @*Results@#We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l 1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. @*Conclusion@#We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

The Expression of Programmed Death-Ligand 1 on Immune Cells Is Related to a Better Prognosis in Biliary Tract Cancer

Background/Aims@#Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. @*Methods@#PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. @*Results@#Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p<0.001; immune cells: HR=0.983, p=0.021). PD-L1 expression in tumor cells was an independent predictor of poor overall survival (HR=1.024, p<0.001). In contrast, PD-L1 expression in immune cells was a predictive marker of good prognosis (HR=0.983, p=0.018). @*Conclusions@#PD-L1 expression in immune cells may be used as an independent factor to evaluate the prognosis of patients with BTC.

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis

Background/Aims@#Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. @*Methods@#We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. @*Results@#Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. @*Conclusions@#We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Neoadjuvant and Adjuvant Chemotherapy for Cholangiocarcinoma / 대한췌담도학회지

Cholangiocarcinoma consists of a heterogeneous group of aggressive and rare malignancies that arise from the bile ducts outside or inside the liver. Although surgical resection remains the only potential curative treatment option for patients with cholangiocarcinoma, curative surgery is only possible in a small number of cases. Furthermore, recurrence rates are high even among patients who undergo surgical resection. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Recently, neoadjuvant chemotherapy has emerged as a promising method to identify patients with poor prognosis, avoiding pathological and non-therapeutic resection, as well as potentially downstaging tumors which cannot be resected initially. This therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant chemotherapy in cholangiocarcinoma and several questions remains unanswered. Adjuvant chemotherapy is administered after surgery to eradicate any remaining cancer cells with the goal of reducing the chances of recurrence. And chemotherapy is also frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear.

A Hybrid Online and Offline International Conference of the Korean Pancreatobiliary Association in Post-COVID-19 Era / 대한췌담도학회지

Background@#/Aim: The COVID-19 pandemic has changed the way of traditional conference and meeting. Since social distancing rule was important issue, many conferences across the world were cancelled or postponed indefinitely. In 2020, International Conference of the Korean Pancreatobiliary Association (IC-KPBA) was held as a hybrid online and offline conference. Here, we report the result of a national survey about online and offline medical conference in Korea. @*Methods@#The survey was performed for both online and offline participants after IC-KPBA. The contents of survey included their way to access the hybrid online-offline conference and satisfaction with the conference format. @*Results@#Total of 78 participants answered the survey and there was no technical problem. Most offline participants were satisfied the prevention measures at conference hall as follows; very satisfied-56%; satisfied-34%. The quality of video and audio were generally satisfactory in both conference hall and virtual conference. ‘Live online lectures’ is the most preferred method of lecture delivery and personal computer with LAN network is preferred to access online conference. Eighty seven percent of offline participants and 91% of online participants answered satisfied and very satisfied, respectively. @*Conclusions@#Participants of IC-KPBA 2020 with hybrid online-offline conference showed a high level of satisfaction.

Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer

Background/Aims@#The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. @*Methods@#The records of patients who received gemcitabine-based FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. @*Results@#SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19-9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell’s C-index of the final prognosis prediction model was 0.62. @*Conclusions@#SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabine-based FL.

Chemotherapy: Knowing When to Start, Evaluate for Response, and Stop / 대한췌담도학회지

Chemotherapy is essential treatment in pancreatobiliary cancer patients. Knowing optimal time of chemotherapy initiation is important. Usually good performance status and general condition without jaundice is first recommendation for initiating chemotherapy. Good performance status is defined as Eastern Cooperative Oncology Group 0-1, with good biliary drainage and adequate nutritional intake. Percutaneous or endoscopic biliary drainage is recommended before chemotherapy in patient who shows high bilirubin level. The optimal timing of chemotherapy after diagnosis is not standardized but guideline recommends chemotherapy less 2 months after initial cancer diagnosis. Regard to chemotherapy response evaluation, Response Evaluation Criteria in Solid Tumors criteria is used per 2-3 months. Response Evaluation Criteria in Solid Tumors criteria evaluate the chemotherapy responsiveness. With regular tumor response, clinicians must determine whether patient can undergo chemotherapy continuously without complication. For example, Eastern Cooperative Oncology Group 3 or poor general condition make patient not to undergo chemotherapy and focus on end-of-life care. As a result, knowing about the start and stop of chemotherapy can help relieve the patient's symptoms, prolong survival and improve the quality of life.

Determinant Factors in Cost to Feed for Long-Term Care Facilities Residents / 보건행정학회지

BACKGROUND: The food and food service influence the quality of life and the general health condition of older persons living in long-term care (LTC) facilities. Purchasing good food materials is a ground of good food service. In Korea, the residents in LTC facilities should pay for the cost of food materials and ingredients out of their pocket because it is not covered by LTC insurance. This study explored what factors affect the cost of food materials paid by LTC facility residents and which factor affects most. METHODS: We used data from the study on out-of-pocket payment on national LTC insurance, which surveyed 1,552 family caregivers of older residents in LTC facilities. We applied conditional multi-level model, of which the first level represents the characteristics of care receivers and caregivers and its second level reflects those of LTC facilities. RESULTS: We found that the facility residents with college-graduated family caregivers paid 11,545 Korean won more than those with less than elementary-graduated ones. However, the income level of family caregivers did not significantly affect the amount of the food material cost of the residents. The residents in privately owned, large, metropolitan-located facilities were likely to pay more than those in other types of facilities. The amount of the food material cost of the residents was mainly decided by the facility level factors rather than the characteristics of care recipients and their family caregivers (intra-class correlation=82%). CONCLUSION: These findings suggest that it might be effective to design a policy targeting facilities rather than residents in order to manage the cost of food materials of residents in LTC facilities. Setting a standard price for food materials in LTC facilities, like Japan, could be suggested as a feasible policy option. It needs to inform the choice of LTC users by providing comparable food material cost information. The staffing requirement of nutritionist also needs to be reviewed.

Bleeding Complications and Clinical Safety of Endoscopic Retrograde Cholangiopancreatography in Patients with Liver Cirrhosis

PURPOSE: Patients with liver cirrhosis are considered to be at risk for additional adverse events during endoscopic retrograde cholangiopancreatography (ERCP). The present study was designed as a propensity-score matched analysis to investigate whether cirrhotic liver increases the risk of bleeding complications in patients undergoing ERCP. MATERIALS AND METHODS: In total, 8554 patients who underwent ERCP from January 2005 to December 2015 were retrospectively analyzed. To adjust for the imbalance between patients with and those without liver cirrhosis, 1:3 propensity score matching was performed according to age and sex. RESULTS: Liver cirrhosis was identified in 264 (3.1%) patients. After propensity score matching, a total of 768 patients were included in each of the cirrhotic (n=192) and non-cirrhotic groups (n=576). Post-procedure bleeding (10.9% vs. 4.7%, p=0.003) was more frequently observed in patients with liver cirrhosis than in those without. In multivariate analyses, liver cirrhosis was identified as an independent risk factor associated with post-ERCP bleeding (p=0.003) after further adjustment for prothrombin time, antiplatelet/coagulant, duration of ERCP, and stent insertion. Child-Pugh (CP) class C was found to be associated with an increased incidence of post-ERCP bleeding in patients with cirrhosis (odds ratio 6.144, 95% confidence interval 1.320–28.606; p=0.021). CONCLUSION: The incidence of post-ERCP bleeding in patients with liver cirrhosis was higher than that in patients without liver cirrhosis. In particular, CP class C cirrhosis was significantly associated with post-ERCP bleeding.

A Case of 47-Years-Old Female with Obstructive Jaundice and Weight Loss / 대한소화기암학회지

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.

Irreversible Electroporation in Patients with Pancreatic Cancer :Angel and Devil / 대한소화기암학회지

Pancreatic cancer has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancer (LAPC) is considered as unresectable because of involvement of celiac and/or mesenteric vessels. The treatment of LAPC is a challenge. Current guidelines suggest systemic therapy. However, the majority of patients will never experience conversion to surgical resection. Thus, in these patients, ablation is an alternative therapy for local control, which causes local destruction while ideally avoiding injury to surrounding healthy tissue. Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. IRE demonstrated to be safe in previous studies. However, it is not free from complications, even serious. Here, we reported two cases of the IRE in LAPC patients.

Clinical Outcomes of Bilateral Stent-in-Stent Placement Using Self-Expandable Metallic Stent for High-Grade Malignant Hilar Biliary Obstruction

PURPOSE: Endoscopic bile duct decompression using bilateral self-expandable metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered a preferred procedure for malignant hilar biliary obstruction (MHBO). However, occlusion thereof occurs frequently. Here, we investigated stent patency duration and risk factors related to stent obstruction with bilateral SIS placement for MHBO at two large centers. MATERIALS AND METHODS: The present study reviewed data on patients with MHBO who underwent endoscopic biliary drainage using the SIS method. Clinical outcomes, including stent patency duration and patient overall survival, were analyzed. Factors associated with stent patency were evaluated using Cox proportional hazards models. RESULTS: Seventy patients with MHBO underwent endoscopic biliary drainage using the SIS method. Median age was 68 years old, and median follow-up duration was 140 days (interquartile range, 57–329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median stent patency duration with the SIS method was 108 days according to Kaplan-Meier curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days. Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as an independent risk factor related to stent patency (p < 0.05). CONCLUSION: In endoscopic biliary decompression using SEMS placed with the SIS method, obstructive jaundice was a risk factor for stent patency. The SIS method for high-grade MHBO showed short stent patency.

Comparison of liquid-based cytology (CellPrepPlus) and conventional smears in pancreaticobiliary disease

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.

Locking Mechanism Failure after Distal Femoral Reconstruction with Modular Universal Tumor and Revision System (MUTARS) Tumor Prosthesis / 대한정형외과학회잡지

PURPOSE: We have used Modular Universal Tumor and Revision System (MUTARS) tumor prosthesis to reconstruct segmental resection defect of the distal femur. The purpose of this study was to evaluate the incidence and pattern of locking mechanism breakage and its correlation with other clinical variables. MATERIALS AND METHODS: We retrospectively reviewed 94 patients who were followed-up for more than one year after tumor prosthesis replacement (MUTARS) between 2008 and 2013. We examined the incidence and timing of locking mechanism (PEEK-OPTIMA) failure. We also evaluated the clinical characteristics of patients experiencing locking mechanism failure and compared them with those of other patients. RESULTS: At a mean follow-up of 55 months, we observed locking mechanism failure in 10 of 94 patients (10.6%). The mean age of patients with locking mechanism failure was 29 years (range, 13-54 years); the mean weight and height were 169 cm (range, 151-181 cm) and 67 kg (range, 53-89 kg), respectively. The mean body mass index was 23.5 kg/m² (range, 20.5-29.4 kg/m²). The median time interval between replacement and locking mechanism failure was 26.5 months (range, 12-72 months). The mean body weight of patients with failure was higher than that of patients without failure (p=0.019). CONCLUSION: The incidence of locking mechanism (PEEK-OPTIMA) failure after distal femoral reconstruction with MUTARS was 11%, and there was a correlation between failure and body weight of patients. Advancements in the design and material of locking mechanisms are warranted to reduce the complication.

Influence of body habitus on the surgical outcomes of bilateral axillo-breast approach robotic thyroidectomy in papillary thyroid carcinoma patients

PURPOSE: Obesity is associated with a number of medical comorbidities and is considered a risk factor for surgical complications. The purpose of this study was to analyze the influence of body habitus including obesity on the surgical outcomes of the Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) in papillary thyroid carcinoma (PTC) patients. METHODS: The medical records of 456 PTC patients who underwent BABA RoT between January 2011 and December 2012 were reviewed, and 310 women PTC patients who had undergone BABA robotic total thyroidectomy with central lymph node dissection were examined. Body habitus were evaluated by measuring body mass index (BMI), body surface area, and neck circumference. We divided the patients into BMI < 25 kg/m2 and BMI ≥ 25 kg/m2 groups. Clinicopathological data, surgical outcomes, and postoperative complications were evaluated. RESULTS: Clinicopathological characteristics did not differ between the 2 BMI groups. The creation of working space time (P = 0.210) and other surgical outcomes showed no significant differences between the groups. There were no statistically significant differences between body habitus indexes and postoperative length of hospital stay, number of retrieved central lymph nodes, postoperative thyroglobulin levels, occurrence of hypoparathyoidism, recurrent laryngeal nerve injury and wound complication. CONCLUSION: Patient with large body habitus undergoing BABA RoT were not at an increased risk of surgical complications and showed good surgical outcomes. BABA RoT may be a good alternative operative method for PTC patients for whom cosmetic outcome is an important consideration.

Influence of body habitus on the surgical outcomes of bilateral axillo-breast approach robotic thyroidectomy in papillary thyroid carcinoma patients

PURPOSE: Obesity is associated with a number of medical comorbidities and is considered a risk factor for surgical complications. The purpose of this study was to analyze the influence of body habitus including obesity on the surgical outcomes of the Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) in papillary thyroid carcinoma (PTC) patients. METHODS: The medical records of 456 PTC patients who underwent BABA RoT between January 2011 and December 2012 were reviewed, and 310 women PTC patients who had undergone BABA robotic total thyroidectomy with central lymph node dissection were examined. Body habitus were evaluated by measuring body mass index (BMI), body surface area, and neck circumference. We divided the patients into BMI < 25 kg/m2 and BMI ≥ 25 kg/m2 groups. Clinicopathological data, surgical outcomes, and postoperative complications were evaluated. RESULTS: Clinicopathological characteristics did not differ between the 2 BMI groups. The creation of working space time (P = 0.210) and other surgical outcomes showed no significant differences between the groups. There were no statistically significant differences between body habitus indexes and postoperative length of hospital stay, number of retrieved central lymph nodes, postoperative thyroglobulin levels, occurrence of hypoparathyoidism, recurrent laryngeal nerve injury and wound complication. CONCLUSION: Patient with large body habitus undergoing BABA RoT were not at an increased risk of surgical complications and showed good surgical outcomes. BABA RoT may be a good alternative operative method for PTC patients for whom cosmetic outcome is an important consideration.

Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer

PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.

Past, Present, and Future of Gastrointestinal Stents: New Endoscopic Ultrasonography-Guided Metal Stents and Future Developments

Innovations in stent technology and technological advances in endoscopic ultrasonography have led to rapid expansion of their use in the field of gastrointestinal diseases. In particular, endoscopic ultrasonography-guided metal stent insertion has been used for the management of pancreatic fluid collection, bile duct drainage, gallbladder decompression, and gastric bypass. Endoscopic ultrasonography-guided drainage of intra-abdominal fluid collections using a plastic or metal stent is well established. Because of the various limitations-such as stent migration, injury and bleeding in the lumen-recently developed, fully covered self-expanding metal stents or lumen-apposing metal stents have been introduced for those fluids management. This article reviews the recent literature on newly developed endoscopic ultrasonography-guided metal stents and the efficacy thereof.

Systemic Chemotherapy in Advanced Pancreatic Cancer

Pancreatic cancer remains one of the most lethal cancers. These patients often have multiple symptoms, and integrated supportive care is critical in helping them remain well for as long as possible. Fluorouracil-based chemotherapy is known to improve overall survival (OS) by approximately 3 months, compared to the best supportive care alone. A 1997 study comparing gemcitabine and fluorouracil treatment of advanced pancreatic cancer patients showed an improvement in OS of 1 month in patients receiving gemcitabine. Over the next 10 years, multiple randomized studies compared single-agent gemcitabine with combination chemotherapy and showed no effective survival improvement. However, the addition of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, was associated with a significant improvement in OS of approximately 2 weeks. However, adoption of this regimen has not been widespread because of its limited effect and added toxicity. Two clinical trials have recently prolonged OS in advanced pancreatic cancer patients by almost 1 year. The first compared FOLFIRINOX with gemcitabine alone, and was associated with a significant improvement in median survival. The second compared gemcitabine and nab-paclitaxel with gemcitabine alone, and was associated with improvements in OS. At present, these regimens are considered standard treatment for patients with good performance statuses.

The Effect of Urocortin 1 on Motility in Isolated, Vascularly Perfused Rat Colon / 대한소화기학회지

BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves. METHODS: Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4+/-7.2%, 48.4+/-20.9%, 67.0+/-25.8%, and 64.2+/-20.9%, respectively) and the motility of distal colon (3.3+/-3.3%, 7.8+/-7.8%, 71.1+/-28.6%, and 87.4+/-32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4+/-2.4% in proximal colon and 3.4+/-3.4% in distal colon (p<0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.