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.

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. @*Materials and Methods@#Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. @*Results@#We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. @*Conclusion@#Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Multi-Center Study on Gender Difference in Resectability and Pathologic Prognosis of Gallbladder Cancer / 대한췌담도학회지

Background@#/Aim: In gallbladder cancer (GBC), gender differences in incidence and mortality rates have been reported with geographic variation. However, there is little known about sex-related difference in GBC prognosis. This study compares prognostic factors according to gender for GBC. @*Methods@#We searched clinicopathological factors in all stages of 952 GBC patients from seven medical centers in Korea. A total of 927 patients were enrolled and surgery with curative resection was performed in 499 patients. @*Results@#Carbohydrate antigen (≥37 U/mL) was a significant prognostic factor in both females and males (odd ratio [OR], 4.30; 95% confidence interval [CI], 3.13-5.89; p2; an independent predictor of poor prognosis via multivariate analysis (OR, 1.03; 95% CI, 1.01-1.05; p=0.005, OR, 1.05; 95% CI, 1.02-1.08; p=0.002). Body mass index (BMI) also showed gender difference, and lower BMI (≤25 kg/m2) was the significant good indicator of multivariate analysis for lymph node metastasis in female patients (OR, 0.42; 95% CI, 0.23-0.77; p=0.005) but, the significant poor indicator of univariate analysis for advanced T-stage in male (OR, 2.79; 95% CI, 1.40-5.54; p=0.003). @*Conclusions@#These results suggest that there is a possibility of gender difference in GBC prognosis. Age and high BMI were poor prognostic factors for curative resection for female GBC patients.

Novel Palliative Chemotherapy for Cholangiocarcinoma / 대한췌담도학회지

The term cholangiocarcinoma (CC) refers to all tumors arising from bile duct epithelium. CCs are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. This leads to a paucity of data from which to define the natural history and optimal treatment regimens. Currently, surgical resection remains the only potentially curative treatment, but many patients develop recurrence. In addition, a limited number of patients can be candidates for curative resection at diagnosis. Therefore, chemotherapy is inevitable choice for the treatment of advanced CC. Gemcitabine plus cisplatin (GP) is considered a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed the superiority of gemcitabine plus cisplatin over gemcitabine alone. Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs. those reported for historical controls treated with gemcitabine-cisplatin alone in a phase II study of 60 patients with locally advanced unresectable or metastatic biliary tract cancer. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. Other active regimens, that could be considered in patients who include have disease progression while receiving GP and who retain an adequate performance status, includes capecitabine plus cisplatin, liposomal irinotecan plus leucovorin-modulated fluorouracil and a fluoropyrimidine alone. We herein review recent published data regarding the use of palliative chemotherapies in CC patients, with a particular focus on novel cytotoxic agents.

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.

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

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.

Prospective Multicenter Study of the Challenges Inherent in Using Large Cell-Type Stents for Bilateral Stent-in-Stent Placement in Patients with Inoperable Malignant Hilar Biliary Obstruction

BACKGROUND/AIMS: Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. METHODS: Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. RESULTS: Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. CONCLUSIONS: Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.

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.

Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. MATERIALS AND METHODS: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening. RESULTS: Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. CONCLUSION: MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.

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.

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.

Chemotherapy for Biliary Tract Cancer / 대한소화기학회지

The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract or the biliary drainage system, including the intra- and extra-hepatic bile ducts as well as the gallbladder. BTCs are aggressive tumors with limited treatment options and poor overall survival. Currently, surgery remains to be the only potentially curative treatment, and most patients develop recurrence. For advanced tumors, only limited effective treatment modalities exist today. Gemcitabine plus cisplatin is considered as a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed superiority of gemcitabine plus cisplatin over gemcitabine alone. In that study, they showed that after a median follow-up of 8.2 months, the median overall survival was 8.1 months in the gemcitabine-only group and 11.7 months in the gemcitabine plus cisplatin group (p<0.001). However, while this is a definite advancement, a 3-month survival extension among patients with BTC is modest at best. Moreover, this regimen has not been compared head-to-head with other gemcitabine based combinations. Gemcitabine monotherapy, 5-fluorouracil plus leucovorin, and single-agent capecitabine are all reasonable options for patients with a borderline performance status. Recent advancements have provided new insight into the genomic landscape of BTCs, and thus, it remains unclear whether combined treatment with molecular targeted agents or other cytotoxic chemotherapeutic agents may also be effective against advanced BTC.

Ampulla of Vater Adenomyoma with Dilatations of Biliary and Pancreatic Duct / 대한췌담도학회지

Adenomyoma is a non-neoplastic lesion that frequently occurs in the gallbladder, but it's rarely found at the ampulla of Vater. When it develops at the ampulla of Vater, it may be mistaken for a periampullary malignancy. A 64-year-old asymptomatic male patient visited to our hospital with abnormal sonogram findings. Abdominal computed tomography and magnetic resonance cholangiopancreatography showed dilatations of common bile duct and main pancreatic duct. However, there was no definite ampullary mass. We performed endoscopic biopsies and endoscopic ultrasonography-guided fine needle aspiration. But the results were negative for malignant cells. Because we could not completely rule out malignancy, pylorus preserving pancreato-duodenectomy was performed. Histologically, hyperplastic components are intermixed with smooth muscle fibers in the subepithelial portion of ampulla of Vater. Awareness of adenomyoma of the ampulla of Vater is very important because of their clinical and endoscopic similarities to ampullary tumors.

A Case of Curative Resection of Advanced Combined Hepatocellular-cholangiocarcinoma after Neoadjuvant Chemotherapy / 대한췌담도학회지

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a primary liver cancer with histopathologic features of both hepatocelluar carcinoma and cholangiocarcinoma. As combined HCC-CC has been associated with poor outcomes, accurate diagnosis and proper treatment planning for patients are considered to be important for improving survival. Currently, surgery is known as the only treatment modality offering potential cure for localized disease. However, there are little published treatment options for advanced or recurrent disease. Furthermore, no published reports exist in respect to the applying successful curative resection after neoadjuvant therapy for advanced combined HCC-CC. Here, we report a case of combined HCC-CC subtype with stem cell feature, intermediate type who underwent curative surgical resection after neoadjuvant chemotherapy consisting of cisplatin and gemcitabine. Pathologic report revealed negative resection margin and follow-up imaging study shows no evidence of tumor recurrence.

Role of Neoadjuvant Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer / 대한췌담도학회지

Surgical resection offers the only chance of cure for nonmetastatic exocrine pancreatic cancer. However, only 15 to 20 percent of patients have potentially resectable disease at diagnosis; approximately 40 percent have distant metastases, and another 30 to 40 percent have locally advanced unresectable tumors. Typically, patients with locally advanced unresectable pancreatic cancer have tumor invasion into adjacent critical structures, particularly the celiac and superior mesenteric arteries. The optimal management of these patients is controversial, and there is no internationally embraced standard approach. Therapeutic options include chemoradiotherapy or chemotherapy alone. While it is reasonable to restage and reevaluate the potential for resectability after neoadjuvant therapy, the frequency of a complete resection and long-term survival is low for patients who initially have categorically unresectable tumors. Others have disease that is categorized as "borderline resectable." While these patients are potentially resectable, the high likelihood of an incomplete resection has prompted interest in strategies to "downstage" the tumor or to increase the likelihood of a margin-negative resection prior to surgical exploration using neoadjuvant therapy. The rationale for neoadjuvant therapy is as follows. First, it is to improve the selection of patients for whom resection will not offer a survival benefit (i.e., those who rapidly progress to metastatic disease during preoperative therapy). Second, it is to increase rates of margin-negative resections, which is the major goal of surgery. Third, it is to start an early treatment of micrometastatic disease. Initial attempt at downstaging with chemotherapy, chemoradiotherapy, or a combination followed by restaging and surgical exploration in responders rather than upfront surgery is suggested.

Phase I Dose-Escalation Study of Proton Beam Therapy for Inoperable Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Inoperable HCC patients who had naive, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade > or = 3 acute toxicity. RESULTS: Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003). CONCLUSION: PBT is safe and effective and an EQD2 > or = 78 GyE10 should be delivered for achievement of local tumor control.

Pneumopericardium Caused by Gastropericardial Fistula after Use of NSAIDs in a Patient with Acute Pericarditis and Gastric Cancer / 대한내과학회지

Here, we report a case of gastropericardial fistula associated with the treatment of acute pericarditis using non-steroidal anti-inflammatory drugs (NSAIDs) in the presence of gastric cancer. The patient presented with acute pericarditis with pericardial effusion that had progressed into definite gastropericardial fistula with pneumopericardium after the administration of NSAIDs. The patient improved after conservative management. Based on the current case, we advise caution when using NSAIDs to treat acute pericarditis in the presence of gastric cancer or possible gastropericardial fistula.

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.

Risk of Pancreatic Cancer in Relation to ABO Blood Group and Hepatitis C Virus Infection in Korea: A Case-Control Study

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.