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.

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).

Predictors of Malignancy in “Pure” Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas without Enhancing Mural Nodules on CT Imaging: A Nationwide Multicenter Study

BACKGROUND/AIMS: Presence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. METHODS: This retrospective study included 180 patients with surgically confirmed “pure” BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy. RESULTS: BD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant. CONCLUSIONS: In patients with “pure” BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.

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.

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.

Clinical outcome of acute nonvariceal upper gastrointestinal bleeding after hours: the role of urgent endoscopy

BACKGROUND/AIMS: This study was performed to investigate the clinical role of urgent esophagogastroduodenoscopy (EGD) for acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) performed by experienced endoscopists after hours. METHODS: A retrospective analysis was performed for consecutively collected data of patients with ANVUGIB between January 2009 and December 2010. RESULTS: A total of 158 patients visited the emergency unit for ANVUGIB after hours. Among them, 60 underwent urgent EGD (within 8 hours) and 98 underwent early EGD (8 to 24 hours) by experienced endoscopists. The frequencies of hemodynamic instability, fresh blood aspirate on the nasogastric tube, and high-risk endoscopic findings were significantly higher in the urgent EGD group. Primary hemostasis was achieved in all except two patients. There were nine cases of recurrent bleeding, and 30-day mortality occurred in three patients. There were no significant differences between the two groups in primary hemostasis, recurrent bleeding, and 30-day mortality. In a multiple linear regression analysis, urgent EGD significantly reduced the hospital stay compared with early EGD. In patients with a high clinical Rockall score (more than 3), urgent EGD tended to decrease the hospital stay, although this was not statistically significant (7.7 days vs. 12.0 days, p > 0.05). CONCLUSIONS: Urgent EGD after hours by experienced endoscopists had an excellent endoscopic success rate. However, clinical outcomes were not significantly different between the urgent and early EGD groups.

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.

MicroRNA-200c as a Prognostic Biomarker for Pancreatic Cancer / 대한소화기학회지

BACKGROUND/AIMS: MicroRNA (miRNA) regulates messenger RNA stability and translation. In cancer biology, miRNA affects the growth and metastasis of cancer cells by controlling epithelial-mesenchymal transition (EMT). MiR-200 family (200a/200b/200c/141) and miR-205 are associated with the regulation of EMT. We investigated the prognostic role of EMT-related miRNAs in pancreatic cancer. METHODS: We analyzed miR-200 family and miR-205 expression in tissue samples of 84 patients who underwent radical resection for pancreatic cancer. RESULTS: Patients were followed from the date of diagnosis until death or censoring. The mean overall survival was 25.0+/-2.0 months (2-140 months). The R0 resection rate was obtained in 84.5% (n=71) of patients. The relative expressions of miR-200a/200b/200c/141 and miR-205 were 266.9+/-57.3/18.5+/-2.2/0.7+/-0.1/27.2+/-6.6 folds and 0.1+/-0.1 compared with human pancreatic ductal epithelial cells, respectively. Overall survival was longer in the low miR-200c expression group than in the high expression group (35 vs. 19 months, p=0.013). Multivariate analysis confirmed that patients with low miR-200c expression survived longer than the high expression group (hazard ratio, 1.771; 95% CI, 1.081-2.900; p=0.023). There was a trend toward longer disease-free survival in low miR-200c group without statistical significance (p=0.061). CONCLUSIONS: The expression of miR-200c may be an important prognosis factor in pancreatic cancer, and it could be a novel therapeutic target of pancreatic cancer.

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.

How to Improve Diagnostic Accuracy in Suspicious Ampullary Lesions?

No abstract available.

How to Improve Diagnostic Accuracy in Suspicious Ampullary Lesions?

No abstract available.

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.

The Efficacy of Moxifloxacin-Containing Triple Therapy after Standard Triple, Sequential, or Concomitant Therapy Failure for Helicobacter pylori Eradication in Korea

BACKGROUND/AIMS: Retreatment after initial treatment failure for Helicobacter pylori is very challenging. The purpose of this study was to evaluate the efficacies of moxifloxacin-containing triple and bismuth-containing quadruple therapy. METHODS: A total of 151 patients, who failed initial H. pylori treatment, were included in this retrospective cohort study. The initial regimens were standard triple, sequential, or concomitant therapy, and the efficacies of the two following second-line treatments were evaluated: 7-day moxifloxacin-containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate 300 mg 4 times a day). RESULTS: The overall eradication rates after moxifloxacin-containing triple therapy and bismuth-containing quadruple therapy were 69/110 (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was performed in the patients who failed standard triple therapy, and the results revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively (p=0.015). The frequency of noncompliance was not different between the two groups, and there were fewer adverse effects in the moxifloxacin-containing triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031, respectively). CONCLUSIONS: Moxifloxacin-containing triple therapy, a recommended second-line treatment for initial concomitant or sequential therapy failure, had insufficient efficacy.

Triple-Tissue Sampling during Endoscopic Retrograde Cholangiopancreatography Increases the Overall Diagnostic Sensitivity for Cholangiocarcinoma

BACKGROUND/AIMS: There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). METHODS: We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. RESULTS: Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively). CONCLUSIONS: TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.

A Case of Fasciola hepatica Infection Mimicking Cholangiocarcinoma and ITS-1 Sequencing of the Worm

Fascioliasis is a zoonotic infection caused by Fasciola hepatica or Fasciola gigantica. We report an 87-year-old Korean male patient with postprandial abdominal pain and discomfort due to F. hepatica infection who was diagnosed and managed by endoscopic retrograde cholangiopancreatography (ERCP) with extraction of 2 worms. At his first visit to the hospital, a gallbladder stone was suspected. CT and magnetic retrograde cholangiopancreatography (MRCP) showed an intraductal mass in the common bile duct (CBD) without proximal duct dilatation. Based on radiological findings, the presumed diagnosis was intraductal cholangiocarcinoma. However, in ERCP which was performed for biliary decompression and tissue diagnosis, movable materials were detected in the CBD. Using a basket, 2 living leaf-like parasites were removed. The worms were morphologically compatible with F. hepatica. To rule out the possibility of the worms to be another morphologically close species, in particular F. gigantica, 1 specimen was processed for genetic analysis of its ITS-1 region. The results showed that the present worms were genetically identical (100%) with F. hepatica but different from F. gigantica.

A Case of Metabolic Encephalopathy Due to Bleeding after EPBD / 대한췌담도학회지

Endoscopic retrograde cholangiopancreatography is widely used for diagnosis and treatment of pancreatobiliary diseases and associated with a spectrum of complications such as pancreatitis, hemorrhage, and so on. Endoscopic papillary balloon dilatation (EPBD) has an advantage over endoscopic sphincterotomy in complication of bleeding. We report here on a 68-year-old woman who developed metabolic encephalopathy due to massive bleeding after EPBD. Massive bleeding was controlled after selective embolization and metabolic encephalopathy was improved after conservative management. Metabolic encephalopathy due to massive bleeding after EPBD has not been reported. We report on this unusual case along with a review of the related literatures.

A Multicenter Phase II Trial of Gemcitabine Plus Oxaliplatin in Unresectable Gallbladder Cancer

BACKGROUND/AIMS: No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). METHODS: Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression. RESULTS: Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. CONCLUSIONS: GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.

Immunoglobulin G4-Related Disease Mimicking Unresectable Gallbladder Cancer

Immunoglobulin G4 (IgG4)-related disease is a novel disease entity that can involve diverse organs, causing specific diseases, including autoimmune pancreatitis, sclerosing cholangitis, cholecystitis, inflammatory aortic aneurysm, and inflammatory pseudotumor. IgG4-related disease is characterized by elevated serum IgG4 concentrations, abundant IgG4 lymphoplasmacytic infiltration, and dramatic steroid responses. It is clinically important to differentiate this rare disease from primary sclerosing cholangitis and cholangiocarcinoma, because the treatment and prognosis of these two diseases are completely different. However, the preoperative diagnosis is challenging, and the disease is frequently misdiagnosed. If the serum level of IgG4 is within the normal range, the diagnosis of IgG4-related disease is more difficult. This article reports on a 59-year-old man with IgG4-related disease mimicking unresectable gallbladder cancer with normal serum IgG4 concentrations.