Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy

Background/Aims@#Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. @*Methods@#We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. @*Results@#One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). @*Conclusions@#The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Background/Aims@#Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes. @*Methods@#We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes. @*Results@#The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107). @*Conclusions@#Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

Genetic Mutation as a Predictive Biomarker for FOLFIRINOX in Patients with Metastatic Pancreatic Adenocarcinoma / 대한소화기학회지

No abstract available.

Extraordinary Response of Metastatic Pancreatic Cancer to Chemotherapy / 대한소화기암학회지

A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m² + nanoparticle albumin-bound paclitaxel 125 mg/m² as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).

Genetic Mutation as a Predictive Biomarker for FOLFIRINOX in Patients with Metastatic Pancreatic Adenocarcinoma / 대한소화기학회지

No abstract available.

Training in Endoscopy: Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) is a key endoscopy skill used to diagnose and treat pancreatobiliary diseases. However, its diagnostic use is decreasing in favor of other less invasive methods such as magnetic resonance cholangiopancreatography and endoscopic ultrasound. Alternatively, its use has become more important in the therapeutic area. ERCP trainees must know the anatomy and physiology of the pancreatobiliary system, several key basic skills, and complications of a successful procedure. This article briefly introduces basic ERCP knowledge, techniques, numbers necessary to achieve competency, and complications for new ERCP operators.

Assessment of Asymptomatically Increased CA 19-9 / 대한췌담도학회지

Health care screening is becoming more popular in Korea as more people are interested in well-being and health. However, there are controversies regarding usefulness of screening. Tumor markers are frequently measured in the health care screening. As a result, many patients end up visiting physicians because of incidentally found increased levels of tumor markers. Carbohydrate antigen (CA) 19-9 is the single most useful tumor marker for pancreatic cancer. Although CA 19-9 is useful for predicting prognosis and evaluating treatment response for pancreatic cancer, CA 19-9 is less useful for screening of pancreatic cancer because of low incidence of pancreatic cancer.

ERCP Educational Guidelines for Fellows / 대한췌담도학회지

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an essential endoscopic technique in diagnosis and treatment of pancreatobiliary diseases. Although its diagnostic role is decreasing because of less invasive modalities such as magnetic resonance cholangiopancreatography or endoscopic ultrasound, it is still very important in treatment of pancreatobiliary diseases. However, there is a trend of hesitation to learn ERCP by the fellows in Korea because of following reasons; concentration of ERCP in a few high volume centers, high risk of post-procedural complications, and long training courses. In this background, the education committee of Korean Pancreatobiliary Association has prepared for ERCP educational guidelines for fellows in Korea. This guideline should be helpful to fellows who are currently under the training.

ERCP Educational Guidelines for Fellows / 대한췌담도학회지

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an essential endoscopic technique in diagnosis and treatment of pancreatobiliary diseases. Although its diagnostic role is decreasing because of less invasive modalities such as magnetic resonance cholangiopancreatography or endoscopic ultrasound, it is still very important in treatment of pancreatobiliary diseases. However, there is a trend of hesitation to learn ERCP by the fellows in Korea because of following reasons; concentration of ERCP in a few high volume centers, high risk of post-procedural complications, and long training courses. In this background, the education committee of Korean Pancreatobiliary Association has prepared for ERCP educational guidelines for fellows in Korea. This guideline should be helpful to fellows who are currently under the training.

A successful rendezvous endoscopic ultrasonography-guided gallbladder drainage in malignant cystic duct obstruction

Endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) has been developed as an alternative drainage method in patients with malignant cystic duct obstruction. However, the procedure of track dilation is difficult in case of severe gallbladder wall thickening with tumor involvement or inflammation. The rendezvous technique via external fistulous track is considered in failed attempts to dilate an internal track between the gallbladder and the stomach/duodenum using conventional approach of EUS-GBD. This report presents a 56-year-old man with pancreatic cancer with malignant cystic duct obstruction who underwent percutaneous transhepatic gallbladder drainage. The patient was successfully treated using rendezvous EUS-GBD technique after he failed the conventional EUS-GBD procedure of internal track dilation.

Etiology and Diagnosis of Chronic Pancreatitis / 대한췌담도학회지

Chronic pancreatitis is an irreversible inflammatory disease of the pancreas characterized by progressive inflammation and fibrosis resulting in loss of exocrine and endocrine function. Chronic pancreatitis is a wide spectrum of fibro-inflammatory disorders of the pancreas that includes calcifying, obstructive, and steroid-responsive form. Chronic pancreatitis without specific comment generally refers to calcifying or obstructive chronic pancreatitis. The well-known traditional causes of chronic pancreatitis are alcohol and smoking. Recently, environmental effects and the importance of genes such as genetic variation or interaction have been highlighted. Computerized tomography or magnetic resonance cholangiopancreatography have been used for diagnosis of chronic pancreatitis. However, endoscopic ultrasound has been recently used for diagnosis, too.

Acute Emphysematous Pancreatitis with Fulminant Multi-organ Failure / 대한췌담도학회지

An emphysematous pancreatitis is a rare, but fatal subtype of acute pancreatitis. Gas-forming bacteria from the bowel may penetrate the pancreas to cause emphysematous pancreatitis. It is characterized by the presence of gas within pancreas bed or retroperitoneal cavity at computed tomographic image and carries a high mortality rate. It requires fluid resuscitation and anti-bacterial therapy to control infection, and needs to consider percutaneous drainage or surgical management depending on the clinical condition. We report a case of 73-year-old patient presented with an emphysematous pancreatitis which developed fulminant multi-organ failure in spite of intensive medical treatment along with a review of the related literatures.

Effects of N-acetylcysteine on First-Line Sequential Therapy for Helicobacter pylori Infection: A Randomized Controlled Pilot Trial

BACKGROUND/AIMS: To evaluate the adjuvant effects of N-acetylcysteine (NAC) on first-line sequential therapy (SQT) for Helicobacter pylori infection. METHODS: Patients with H. pylori infections were randomly assigned to receive sequential therapy with (SQT+NAC group, n=49) or without (SQT-only group, n=50) NAC. Sequential therapy consisted of rabeprazole 20 mg and amoxicillin 1 g for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the remaining 5 days; all drugs were administered twice daily. For the SQT+NAC group, NAC 400 mg bid was added for the first 5 days of sequential therapy. H. pylori eradication was evaluated 4 weeks after the completion of therapy. RESULTS: The eradication rates by intention-to-treat analysis were 58.0% in the SQT-only group and 67.3% in the SQT+NAC group (p=0.336). The eradication rates by per-protocol analysis were 70.0% in the SQT-only group and 80.5% in the SQT+NAC group (p=0.274). Compliance was very good in both groups (SQT only/SQT+NAC groups: 95.2%/100%, p=0.494). There was no significant difference in the adverse event rates between groups (SQT-only/SQT+NAC groups: 26.2%/26.8%, p=0.947). CONCLUSIONS: The H. pylori eradication rate was numerically higher in the SQT+NAC group than in the SQT-only group. As our data did not reach statistical significance, larger trials are warranted.

MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers

BACKGROUND/AIMS: In recent years, a large number of micro-ribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. METHODS: From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2−ΔΔCt method. RESULTS: In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. CONCLUSIONS: Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease.

A Case of Idiopathic Severe Acute Pancreatitis following Cesarean Section Delivery / 대한소화기학회지

Acute pancreatitis rarely occurs in the postpartum period. Furthermore, there are very few reports of it after cesarean section delivery. A 35-year-old woman presented with dyspnea and abdominal distension on the third day after cesarean section delivery. Under a suspicion of acute pancreatitis, she was initially managed with conservative treatment. However, she developed intra-abdominal fluid collections and gastric bleeding, which were managed with percutaneous drainage, endoscopic hemostasis, and angiographic embolization. She was discharged with good clinical recovery. Postpartum pancreatitis, especially after cesarean section, is rare; however, its management is not different from that for usual pancreatitis.

Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study

BACKGROUND/AIMS: Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome. METHODS: A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85). RESULTS: The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period. CONCLUSIONS: Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.

Endoscopic Ultrasound-Guided Treatment of Pancreatic Cystic and Solid Masses

Pancreatic tumor is one of the most difficult diseases to diagnose and treat because of its anatomical location and characteristics. Recently, there have been several innovative trials on the treatment of pancreatic tumors using endoscopic ultrasound (EUS) because it allows selective access to the difficult to reach target organ along the gastrointestinal tract and can differentiate vessels by color Doppler. Among these trials, several have investigated EUS-guided ethanol lavage with or without paclitaxel for pancreatic cystic tumors. These studies show a 33% to 79% complete resolution rate with a favorable safety profile. Compared to EUS-guided ethanol lavage for pancreatic cystic tumors, EUS-guided radiofrequency ablation is considered a less invasive treatment method for pancreatic cancer. Although there are still several difficulties and concerns about complications, one clinical study reported 72.8% feasibility with favorable safety, and therefore, we anticipate the results of ongoing studies with these new less invasive techniques.

Postoperative Carcinoembryonic Antigen as a Complementary Tumor Marker of Carbohydrate Antigen 19-9 in Pancreatic Ductal Adenocarcinoma

The role of carcinoembryonic antigen (CEA) in pancreatic cancer remains poorly understood. Therefore, this study aimed to determine whether CEA is complementary to carbohydrate antigen 19-9 (CA19-9) in prognosis prediction after pancreatic cancer curative resection. We retrospectively reviewed records of 144 stage II curatively resected pancreatic cancer patients with preoperative and postoperative CEA and CA19-9 levels. Patients with normal preoperative CA19-9 were excluded. R0 resection margin, adjuvant treatment, and absence of angiolymphatic invasion were associated with better overall survival. There was no significant difference in median survival according to preoperative CEA levels. However, patients with normal postoperative CA19-9 (59.8 vs.16.2 months, P < 0.001) and CEA (29.4 vs. 9.3 months, P = 0.001) levels had longer overall survival than those with elevated levels. Among 76 patients with high postoperative CA19-9 levels, a better prognosis was observed in those with normal postoperative CEA levels than in those with elevated levels (19.1 vs. 9.3 months, P = 0.004). Postoperative CEA and CA19-9 levels are valuable prognostic markers in resected pancreatic cancer. Normal postoperative CEA levels indicate longer survival, even in patients with elevated postoperative CA19-9.

Which Is the Better Treatment for the Removal of Large Biliary Stones? Endoscopic Papillary Large Balloon Dilation versus Endoscopic Sphincterotomy

BACKGROUND/AIMS: We evaluated the efficacy and cost-effectiveness of endoscopic papillary large balloon dilation (EPLBD) for large common bile duct (CBD) stone removal compared with endoscopic sphincterotomy (EST). METHODS: A total of 1,580 patients who underwent endoscopic CBD stone extraction between January 2001 and July 2010 were reviewed. The following inclusion criteria were applied: choledocholithiasis treated by EPLBD with minor EST or EST with mechanical lithotripsy; and follow-up >9 months after treatment. RESULTS: Forty-nine patients with EPLBD and 41 with EST were compared. There was no significant difference in the complication rates and stone recurrence rates between the two groups. However, significantly more endoscopic retrograde cholangiopancreatography (ERCP) sessions were required in the EST group to achieve the complete removal of stones (1.7 times vs 1.3 times; p=0.03). The mean cost required for complete stone removal per patient was significantly higher in the EST group compared to the EPLBD group (USD $1,644 vs $1,225, respectively; p=0.04). Dilated CBD was the only significant factor associated with recurrent biliary stones (relative risk, 1.09; 95% confidence interval, 1.02 to 1.17; p=0.02). CONCLUSIONS: EPLBD is the better treatment (compared to EST) for removing large CBD stones because EPLBD requires fewer ERCP sessions and is less expensive.

Primary Aortoenteric Fistula to the Sigmoid Colon in Association with Intra-abdominal Abscess / 대한소화기학회지

Primary aortoenteric fistula (PAEF) is a rare but catastrophic cause of massive gastrointestinal bleeding. Diagnosis of PAEF is difficult to make and is frequently delayed without strong clinical suspicion. Timely surgical intervention is essential for patient's survival. We report on a case of an 86-year-old woman with no history of abdominal surgery, who presented with abdominal pain. Initially, computed tomography scan showed an intra-abdominal abscess, located anterior to the aortic bifurcation. However, she was discharged without treatment because of spontaneous improvement on a follow-up computed tomography scan, which showed a newly developed right common iliac artery aneurysm. One week later, she was readmitted due to recurrent abdominal pain. On the second day of admission, sudden onset of gastrointestinal bleeding occurred for the first time. After several endoscopic examinations, an aortoenteric fistula bleeding site was found in the sigmoid colon, and aortography showed progression of a right common iliac artery aneurysm. We finally concluded that intra-abdominal abscess induced an infected aortic aneurysm and enteric fistula to the sigmoid colon. This case demonstrated an extremely rare type of PAEF to the sigmoid colon caused by an infected abdominal aortic aneurysm, which has rarely been reported.