Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. @*Materials and Methods@#Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. @*Results@#PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). @*Conclusion@#Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Efficacy of ferric carboxymaltose in iron deficiency anemia patients scheduled for pancreaticoduodenectomy

Purpose@#Perioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD. @*Methods@#Twenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1–3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated. @*Results@#The perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively). @*Conclusions@#FCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.

Trend Analysis and Prediction of Hepatobiliary Pancreatic Cancer Incidence and Mortality in Korea

Background@#This study aimed to analyze the current trends and predict the epidemiologic features of hepatobiliary and pancreatic (HBP) cancers according to the Korea Central Cancer Registry to provide insights into health policy. @*Methods@#Incidence data from 1999 to 2017 and mortality data from 2002 to 2018 were obtained from the Korea National Cancer Incidence Database and Statistics Korea, respectively. The future incidence rate from 2018 to 2040 and mortality rate from 2019 to 2040 of each HBP cancer were predicted using an age-period-cohort model. All analyses, including incidence and mortality, were stratified by sex. @*Results@#From 1999 to 2017, the age-standardized incidence rate (ASIR) of HBP cancers per 100,000 population had changed (liver, 25.8 to 13.5; gallbladder [GB], 2.9 to 2.6;bile ducts, 5.1 to 5.9; ampulla of Vater [AoV], 0.9 to 0.9; and pancreatic, 5.6 to 7.3). The age-standardized mortality rate (ASMR) per 100,000 population from 2002 to 2018 of each cancer had declined, excluding pancreatic cancer (5.5 to 5.6). The predicted ASIR of pancreatic cancer per 100,000 population from 2018 to 2040 increased (7.5 to 8.2), but that of other cancers decreased. Furthermore, the predicted ASMR per 100,000 population from 2019 to 2040 decreased in all types of cancers: liver (6.5 to 3.2), GB (1.4 to 0.9), bile ducts (4.3 to 2.9), AoV (0.3 to 0.2), and pancreas (5.4 to 4.7). However, in terms of sex, the predicted ASMR of pancreatic cancer per 100,000 population in females increased (3.8 to 4.9). @*Conclusion@#The annual incidence and mortality cases of HBP cancers are generally predicted to increase. Especially, pancreatic cancer has an increasing incidence and will be the leading cause of cancer-related death among HBP cancers.

First Course of treatment and Prognosis of Exocrine Pancreatic Cancer in Korea from 2006 to 2017 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Hospital-based clinical studies have limitations in holistic assessment of cancer treatment and prognosis, as they omit out-of-hospital patients including elderly individuals. This study aimed to investigate trends in initial treatment and corresponding prognosis of patients with exocrine pancreatic cancer (EPC) in Korea. @*Materials and Methods@#The Korea Central Cancer Registry data of patients with EPC from 2006 to 2017 were retrospectively reviewed. We defined the first course of treatment (FT) as the cancer-directed treatment administered within four months after cancer diagnosis according to Surveillance, Epidemiology, and End Results (SEER) program. @*Results@#Among 62,209 patients with EPC, localized and regional (LR) SEER stage; patients over 70 years old; and ductal adenocarcinoma excluding cystic or mucinous (DAC) accounted for 40.6%, 50.1%, and 95.9%, respectively. “No active treatment” (NT, 46.5%) was the most frequent, followed by non-surgical FT (28.7%) and surgical FT (22.0%). Among 25,198 patients with LR EPC, surgical FT increased (35.9% to 46.3%) and NT decreased (45.0% to 29.5%) from 2006 to 2017. The rate of surgical FT was inversely related to age (55.1% [< 70 years], 37.3% [70-79 years], 10.9% [≥ 80 years]). Five-year relative survival rates of LR DAC were higher after surgical FT than after NT in localized (46.1% vs. 12.9%) and regional stage (23.6% vs. 4.9%) from 2012 to 2017. @*Conclusion@#Less than half of overall patients with LR EPC underwent surgical FT, and this proportion decreased significantly in elderly individuals. Clinicians should focus attention on elderly patients with EPC to provide appropriate medical advice.

Perioperative Management of Morbidly Obese Patients during Major Abdominal Surgery

The population with obesity is seeing a steady increase globally. Obesity is known to be associated with morbidity and mortality after major abdominal surgery, and this correlation becomes more prominent in morbidly obese (MO) patients. Accordingly, adequate preoperative evaluation and preparation should be performed with an understanding of the pathophysiological changes associated with the MO. Precise surgery and adequate postoperative management are also mandatory to reduce complications and unplanned readmissions. However, adequate guidelines for the perioperative management of MO patients undergoing major abdominal surgery are lacking. We provide an overview of the pathophysiologic changes and practical guidelines on the perioperative management of major abdominal surgery in MO patients.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Rhus verniciflua Stokes extract suppresses migration and invasion in human gastric adenocarcinoma AGS cells

BACKGROUND/OBJECTIVES@#Many studies have suggested that Rhus verniciflua Stokes (RVS) and its extract are anticancer agents. However, RVS had limited use because it contains urushiol, an allergenic toxin. By improving an existing allergen-removal extraction method, we developed a new allergen-free Rhus verniciflua Stokes extract (RVSE) with higher flavonoid content. In this study, we examined whether RVSE inhibits the ability of AGS gastric cancer cells to migrate and invade.MATERIALS/METHODS: The flavonoids content of RVSE was analyzed by HPLC. The effects of RVSE on migration and invasion in AGS cells were analyzed by each assay kit. Matrix metalloproteinase (MMP)-9, plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA) protein expression was analyzed by protein antibody array. The Phosphorylation of signal transducer and activator of transcription (STAT) 3 were assayed by Western blot analysis. @*RESULTS@#RVSE treatment with 0–100 μg/mL dose-dependently reduced the ability of AGS cells to migrate and invade. Notably, treatment with RVSE strongly inhibited the expression of MMP-9 and uPA and the phosphorylation of STAT3. In contrast, RVSE treatment dramatically increased the expression of PAI-1. These results indicate that the inhibition of MMP-9 and uPA expression and STAT3 phosphorylation and the stimulation of PAI-1 expression contributed to the decreased migration and invasion of AGS cells treated with RVSE. @*CONCLUSIONS@#These results suggest that RVSE may be used as a natural herbal agent to reduce gastric cancer metastasis.

Comprehensive Cancer Panel Sequencing Defines Genetic Diversity and Changes in the Mutational Characteristics of Pancreatic Cancer Patients Receiving Neoadjuvant Treatment

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDA) is associated with an extremely poor prognosis. This study assessed the genetic diversity among patients with PDA and compared their mutational profiles before and after treatment. METHODS: Tumors and matched blood samples were obtained from 22 PDA patients treated with neoadjuvant chemoradiation therapy. The somatic mutations were analyzed with comprehensive cancer gene panel (CCP). In addition, the biopsy samples obtained at diagnosis and the surgically resected samples after treatment were compared for seven patients. The CCP provided formalin-fixed paraffin-embedded sample-compatible multiplexed target selection for 409 genes implicated in cancer. RESULTS: Assessments of the MLH1, MLH3, MSH2, and PMS2 genes showed that the four patients with the highest relative burdens of mutations harbored somatic mutations in at least three of these genes. Genes in the histone-lysine N-methyltransferase 2 (KMT2) family, such as KMT2D, KMT2A, and KMT2C, were frequently mutated in tumor samples. Survival was worse in patients with ARID1A gene mutations than those without ARID1A gene mutations. Mutation patterns were compared between tissue samples before and after neoadjuvant treatment in seven patients who underwent surgical resection. The allelic fraction of mutations in KRAS codon 12 was lower in the surgically resected samples than in the endoscopic ultrasonography-guided fine needle aspiration biopsy samples of six patients. The number of mutant alleles of the histone lysine methyltransferase gene WHSC1 also decreased after treatment. CONCLUSIONS: These results indicate that tumor tissue from PDA patients is genetically diverse and suggest that ARID1A mutations may be a potential prognostic marker for PDA.

Repeat hepatectomy for recurred colorectal liver metastasis: is it justified?

PURPOSE: Liver resection is considered the only curative treatment modality for colorectal liver metastasis. The recurrence rate after hepatectomy is >50%. Two or more hepatectomies are applied to treat recurred metastases. We assessed the efficiency and feasibility of repeat hepatectomy and analyzed the prognostic factors after a repeat hepatectomy. METHODS: In total, 248 patients were diagnosed with recurred liver metastasis between January 2003 and May 2016. Second and third hepatectomies were performed in 70 and 7 patients, respectively. The other 171 patients did not undergo a repeat hepatectomy. Clinical features were collected from the medical records. We analyzed survival rates of the repeat hepatectomy group and the nonrepeat hepatectomy group. We also investigated factors affecting overall and disease-free survival of patients who received a repeat hepatectomy using univariate and multivariate analyses. RESULTS: Median overall survival was significantly higher in the repeat hepatectomy group than in the nonrepeat group (83.0 months vs. 25.0 months, P < 0.001). The morbidity and mortality rates of repeat hepatectomy were 9.1% and 0%, respectively. Median overall and disease-free survival of the repeat hepatectomy group were 62.0 and 51.0 months, respectively. The number of recurred tumors was the only significant factor for disease-free survival (P = 0.029). None of the factors affected overall survival. CONCLUSION: Repeat hepatectomy is necessary, effective, and safe for treating recurred colorectal liver metastasis. Repeat hepatectomy can be considered in patients with fewer than three recurred metastatic tumors.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

Effectiveness and feasibility of concurrent chemoradiotherapy using simultaneous integrated boost-intensity modulated radiotherapy with and without induction chemotherapy for locally advanced pancreatic cancer

PURPOSE: To evaluate the effectiveness and feasibility of chemoradiotherapy (CRT) using simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: Between January 2011 and May 2015, 47 LAPC patients received CRT using SIB-IMRT. Prior to SIB-IMRT, 37 patients (78.7%) received induction chemotherapy (IC-CRT group) and remaining 10 patients (21.3%) did not received induction chemotherapy (CRT group). During SIB-IMRT, all patients received concomitant chemotherapy, with gemcitabine (n = 37) and capecitabine (n = 10). RESULTS: At the time of analysis, 45 patients had died and 2 patients remained alive and the median follow-up time was 14.2 months (range, 3.3 to 51.4 months). For all patients, the median times of local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were 18.1, 10.3, and 14.2 months, respectively. The median time of LPFS between IC-CRT and CRT groups was similar (18.1 months vs. 18.3 months, p = 0.711). IC-CRT group had a higher trend in PFS (10.9 months vs. 4.1 months, p = 0.054) and had significantly higher OS (15.4 months vs. 9.5 months, p = 0.007) than CRT group. In multivariate analysis, the use of induction chemotherapy and tumor response were significant factors associated with OS (p < 0.05, each). During SIBIMRT, toxicity of grade ≥3 was observed in 7 patients (14.9%) in all patients. CONCLUSIONS: CRT using SIB-IMRT is feasible and promising in LAPC patients.

Proximal Resection Margins: More Prognostic than Distal Resection Margins in Patients Undergoing Hilar Cholangiocarcinoma Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Even though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors. MATERIALS AND METHODS: We reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival. RESULTS: Negative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors. CONCLUSION: A clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status.

Somatic Mutations from Whole Exome Sequencing Analysis of the Patients with Biliary Tract Cancer

Biliary tract cancer (BTC) is a rare cancer and is associated with a poor prognosis. To understand the genetic characteristics of BTC, we analyzed whole-exome sequencing data and identified somatic mutations in patients with BTC. Tumors and matched blood or normal samples were obtained from seven patients with cholangiocarcinoma who underwent surgical resection. We discovered inactivating mutations of tumor suppressor genes, including APC, TP53, and ARID1A, in three patients. Activating mutations of KRAS and NRAS were also identified. Our analyses identified somatic mutations in Korean patients with BTC

A prospective randomized study comparing radiofrequency ablation and hepatic resection for hepatocellular carcinoma

PURPOSE: Although there are several prospective clinical studies comparing radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma, there are few trials that have been performed in strictly homogeneous patients. METHODS: Patients who were newly diagnosed with a solitary hepatocellular carcinoma were randomized to the HR or RFA group. Inclusion criteria were as follows: age ≥ 20 years but ≤ 70 years, Child-Pugh class A, maximal diameter of the tumor ≥ 2 cm but ≤ 4 cm, no previous treatment history, and platelet count > 80,000/mm3. RESULTS: Although the study was early terminated, 29 and 34 patients were enrolled in the HR and RFA groups, respectively, and prospectively followed on an intention-to-treat basis. The 5-year overall survival rates were 83.4% and 86.2% in the HR and RFA groups, respectively, which were not significantly different (P = 0.812 by log-rank, P = 0.990 by Breslow). The 3- and 5-year disease-free survival rates in the HR group were significantly superior to those in the RFA group (66.7%, 44.4% vs. 44.1%, 31.2%, P = 0.071 by log-rank, P = 0.023 by Breslow). Intrahepatic local recurrence tended to develop more frequently in the RFA group (P = 0.042), while the frequency of intrahepatic distant and extrahepatic recurrence was similar bet ween the 2 groups. There were no significant differences in the frequency and severity of complications between the 2 groups. CONCLUSION: HR was significantly superior to RFA in terms of disease-free survival; however, the overall survival was excellent in both groups.

Are you prepared for pancreas bifidum? A case report

Pancreas divisum—failure of fusion of the dorsal and ventral pancreatic ducts—is relatively well known as the most common congenital anomaly of the pancreatic duct, of with an incidence approximately 10% of all embryos. And there is a rare anomaly similar to pancreas divisum in which doubled ducts are formed. This condition is a rare developmental anomaly called pancreas bifidum or bifid pancreas or fish tail pancreas. This report describes a patient with pancreas bifidum who had 2 separated ducts within the pancreas from tail to neck but did not have a separated parenchyma. We hope that this report helps pancreatic surgeons to have knowledge of pancreas bifidum and helps them to be prepared for this anatomical variant.

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer. MATERIALS AND METHODS: In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m²) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA). RESULTS: Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001). CONCLUSION: Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

Successful early application of extracorporeal membrane oxygenation to support cardiopulmonary resuscitation for a patient suffering from severe malignant hyperthermia and cardiac arrest: a case report / 대한마취과학회지

Malignant hyperthermia (MH) may lead to metabolic crisis of skeletal muscle in susceptible individuals following exposure to triggering agents such as volatile anesthetics or depolarizing muscle relaxants. MH is a rare and a potentially lethal disease, which can lead to cardiac arrest. We report a case of severe MH, in which the rapidly evolving signs of hypermetabolism eventually resulted in cardiac arrest. Despite conventional treatments following cardiopulmonary resuscitation, the patient's vital signs did not improve. Therefore, we applied extracorporeal membrane oxygenation for providing hemodynamic support.

Effect of Capecitabine plus Oxaliplatin for Advanced Adenocarcinoma of Ampulla of Vater / 대한췌담도학회지

BACKGROUND/AIM: Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of palliative chemotherapy. We investigated the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with advanced ampullary adenocarcinoma. METHODS: From October 2006 to January 2014, we retrospectively analyzed 28 patients with advanced ampullary adenocarcinoma treated by XELOX regimen at single institution. All the patients had histologically confirmed stage IV or recurrent ampullary adenocarcinoma. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. RESULTS: With follow-up of median 24.6 months (range 4.0–78.0 months), median progression-free survival (PFS) was 4.8 months (range 0.7–26.1 months), and median overall survival (OS) was 11.9 months (range 2.0–36.0 months). One patient (4%) achieved complete response and 5 patients (18%) showed partial response. There were no significant differences for PFS and OS according to response by chemotherapy. The most common grade 3 adverse events in patients were nausea and vomiting (10.7%). There was no treatment-related mortality. CONCLUSIONS: XELOX regimen is well tolerated and show moderate activity against advanced ampullary adenocarcinoma.

Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed 2 µg/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 µg/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ≥ 50 mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.