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Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P < 0.0001) colorectal cancers. This trend was also observed in colon polyps (CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer. Cancer Prev Res; 8(8); 702–11. ©2015 AACR.

Supplementary Table 2. Primer sets for pyrosequencing methylation analysis, mutation analysis, and RT-PCR

Supplementary Fig. 2. Genetic and epigenetic alterations in CIMP-P CRCs

Supplementary Fig. 1. DNA methylation and expression analyses in TET1

Supplementary Table 4. Relationship between TET1 methylation and Clinical features in CIMP-P CRCs (TCGA data set)

Supplementary Figure legends for Supplementary Fig.1 and Fig. 2

Supplementary Table 3. Relationship between TET1 methylation and other mutation and methylation markers in CIMP-P CRCs (in our cohort)

PDF file, 49KB.

Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-γ ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS).Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers α-fetoprotein and/or des-γ-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N = 15) than in those with low frequencies (N = 18; P = 0.033).Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination. Clin Cancer Res; 18(13); 3686–96. ©2012 AACR.

PDF file, 60KB, Expression of GPC3 and HLA class I in cases 8 and 25 was determined by immunohistochemistry. Magnification = 200�.

PDF file, 28KB, The levels of AFP or DCP decreased temporarily at least once in nine of the 33 patients. In seven of these nine patients, the levels of DCP fell to < 30% of baseline values.

PDF file, 36KB, A 30 mg dose of peptide caused stronger local skin reactions (blushing, induration) at the injection site than did a 3.0 mg dose.

PDF file, 47KB, There was no significant difference in the clinical background of patients with GPC3-specific CTL frequencies ≥ 50 and those with < 50. A peptide dose of greater than 1.0 mg was required for adequate induction of GPC3-specific CTL frequences ≥ 50.

A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. Although highly invasive, surgery is often used as the first-line treatment. We herein report the case of a 65-year-old woman who presented with complaints of progressive odynophagia and dysphagia for 2 weeks following a fish meal. Enhanced cervicothoracic computed tomography demonstrated an enhanced round mass with peripheral contrasted margins. The mass was diagnosed as a mediastinal abscess resulting from esophageal perforation caused by a fish bone. Endoscopic ultrasound-guided abscess drainage (EUS-AD) was performed using a nasobiliary drainage tube (NDT). Two weeks later, the abscess had completely disappeared. EUS-AD was safe and effective in this case; furthermore, external drainage using NDT was suitable for this abscess located very close to the upper esophageal sphincter.

Objectives Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for solid pancreatic lesions has high diagnostic yield. However, few prospective multicenter studies have been performed. We performed a prospective cohort study to evaluate the efficacy and safety of EUS-FNA for diagnosis of solid pancreatic lesions. Methods This prospective cohort study involved five hospitals in Japan. The primary outcome was sensitivity of EUS-FNA for diagnosing malignant lesions. We also evaluated parameters of diagnostic sufficiency and the safety of EUS-FNA. Results In total, 246 patients were enrolled. The absolute values of the parameters evaluated showed no significant differences; however, the percentage changes in the white blood cell counts and C-reactive protein levels after examination were significantly higher, and the percentage change in hemoglobin concentrations was significantly lower. The minor and major complication rates at the time of puncture, 24 h, 7 days and 28 days were 4.1%, 2.8%, 1.6%, and 0.0%, respectively. The true complication rate was 1.2%. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97.2%, 88.0%, 96.2%, 100%, and 81.4%, respectively. Conclusions EUS-FNA for solid pancreatic lesions has high diagnostic yield and is safe, consistent with previously studies.

Endoscopic ultrasound/ultrasonography‐guided biliary drainage (EUS‐BD) is a relatively new modality for biliary drainage after failed or difficult transpapillary biliary cannulation. Despite its clinical utility, EUS‐BD can be complicated by severe adverse events such as bleeding, perforation, and peritonitis. The aim of this paper is to provide practice guidelines for safe performance of EUS‐BD as well as safe introduction of the procedure to non‐expert centers. The guidelines comprised patient–intervention–comparison–outcome‐formatted clinical questions (CQs) and questions (Qs), which are background statements to facilitate understanding of the CQs. A literature search was performed using the PubMed and Cochrane Library databases. Statement, evidence level, and strength of recommendation were created according to the GRADE system. Four committees were organized: guideline creation, expert panelist, evaluation, and external evaluation committees. We developed 13 CQs (methods, device selection, supportive treatment, management of adverse events, education and ethics) and six Qs (definition, indication, outcomes and adverse events) with statements, evidence levels, and strengths of recommendation. The guidelines explain the technical aspects, management of adverse events, and ethics of EUS‐BD and its introduction to non‐expert institutions., Highlight Isayama and colleagues present the first clinical practice guidelines for endoscopic ultrasound‐guided biliary drainage (EUS‐BD), including indications, clinical results, procedures, devices and education. Their primary purpose is to improve the outcomes of EUS‐BD for biliary tract diseases by facilitating the safe introduction and performance of the procedure at non‐expert centers.

Background : Endoscopic-guided placement of metal stents for unresectable malignant hilar biliary obstruction (UMHBO) is performed using partial stent-in-stent or side-by-side (SBS) techniques. The latter involves placing sequential stents within the bile duct. Excessive dilation of the bile duct during stent placement can have serious effects on the surrounding organs. Methods : This study details seven cases of SBS placement of 8.0 mm metal stents for UMHBO. Histopathological examinations were performed to identify the effects on the bile duct and surrounding tissues. Results : The mean post-placement diameter of the bile ducts was 13.86 mm, and no compression necrosis or thrombi were observed in surrounding tissues. Cholangitis occurred in five cases, and death occurred as a result of cholecystitis in one case. Conclusion : The use of 8.0-mm stents for SBS is unlikely to have major negative effects on peribiliary tissues and blood vessels. However, post-placement cholecystitis can result in increased mortality; thus, gallbladder drainage should be considered.

Upon abdominal ultrasonography, a woman in her 36 years old was diagnosed with a hypoechoic tumor with a diameter of 60mm surrounding the bile duct in the hepatic portal region. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a tumor-like mass in the bile duct. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the diagnosis of schwannoma. Considering the lesion location, it appeared to rise from the hepatoduodenal ligament. She was unwilling to undergo tumor resection;however, a year after the diagnosis, no change was observed in the tumor. Here, we report a case of schwannoma in the hepatoduodenal ligament, wherein EUS-FNA was useful for establishing a diagnosis and determining a treatment strategy.

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cell-free (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD-ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD-ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-sequencing analysis in cancer tissues and corresponding cfDNA revealed that more than 80% of methylated regions were overlapping; DNA methylation profiles of cancerous tissues and cfDNA significantly correlated with each other (R = 0.97). Our data indicate that newly developed MBD-ddPCR is a sensitive method to detect cfDNA methylation and that using five marker genes plus KRAS mutations may be useful for the detection of pancreatic cancers.

There have been no reports of ruptured solid pseudopapillary neoplasm (SPN) into adjacent organs. A 22-year-old female was referred to our hospital for treatment of a pancreatic head tumor. Computed tomography (CT) examination at our hospital showed a 5-cm tumor containing air, although CT at a previous hospital revealed an 8-cm tumor without air. Thus, a spontaneous rupture of the tumor into the duodenum was suspected. Subtotal stomach preserving pancreaticoduodenectomy with combined resection of the portal vein was performed. Contrast radiography of resected specimen showed the medium injected into the tumor leaking out from the 2nd portion of the duodenum. Histologically, the patient was diagnosed as SPN. Microscopic invasion to the portal vein and duodenum were also confirmed. She did not experience any postoperative complications and has remained well without any signs of recurrence during 2 years of follow-up. Although there have been 14 studies reporting ruptured SPN, this is the first report of SPN that spontaneously ruptured into the duodenum. An extremely rare case of SPN of the pancreatic head that spontaneously ruptured into the duodenum was reported.

Background and Aims EUS-guided choledochoduodenostomy (EUS-CDS) using conventional tubular stents has been successfully performed. However, EUS-CDS carries a high risk of bile leakage with attendant adverse events. This study aimed to prospectively evaluate the long-term outcome of EUS-CDS using a dedicated lumen-apposing metal stent (LAMS). Methods Nineteen patients (mean age, 70.6 years; 12 men) with unresectable malignant diseases were treated in 5 tertiary referral centers. EUS-CDS was performed using a fully covered LAMS with a cautery-enhanced delivery system for EUS-CDS. Results All stents were successfully deployed without any adverse events. Jaundice improved in 79% of the patients within 7 days and finally in 95%. In 95% of patients the stents remained in good anastomotic position without migration or dislocation during the follow-up period (median, 184 days; range, 12-819). One patient had a fever the day after stent placement. During the follow-up period 5 patients had secondary stent obstruction because of food residue (n = 2), kinking (n = 1), suspected tumor ingrowth (n = 1), and spontaneous dislodgement (n = 1). Five patients developed obstruction in the second portion of the duodenum. The overall adverse event rate was 36.8% (7/19), mostly with mild severity. Conclusions This study revealed that the novel dedicated LAMS used has high technical and clinical success rates for EUS-CDS. The adverse events and patency rates are inferior to the historically reported data of a conventional transpapillary metal stent. Development of a more suitable dedicated LAMS is anticipated.

A 68-year-old man with a history of diabetes mellitus was admitted to our hospital with a diagnosis of acute pancreatitis. Abdominal computed tomography revealed a suspicious tumor in the body of the pancreas, along with a dilated main pancreatic duct and edema of the pancreatic tail. Endoscopic retrograde pancreatography was performed after treating the patient's pancreatitis. When a cannula tip was advanced beyond the stenosis, deep into the distal pancreatic duct, thick white pus was evacuated. A bacteriological examination of the aspirated pancreatic juice revealed Enterobacter cloacae, and a cytological examination revealed adenocarcinoma. The diagnosis was acute obstructive suppurative pancreatic ductitis associated with pancreatic carcinoma.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

A young woman with Li-Fraumeni syndrome (LFS) was referred to our hospital. On examination, multiple flat neoplasms were detected in addition to semi-pedunculated polyps. Restorative proctocolectomy was performed; one submucosal invasive cancer, two mucosal cancers, and several adenomas with high-grade dysplasia were detected. On immunohistochemical staining with p53, every part of all neoplasms, even the small adenomas, showed strong positive staining. Multiple flat neoplasms may be characteristic of patients with LFS and may have a much higher risk of rapid progression to invasive carcinomas than sporadic neoplasms. Thus, careful and frequent colonoscopy surveillance may be needed for patients with LFS.

Objective The endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a salvage method for failed selective biliary cannulation. Three puncture routes have been reported, with many comparisons between the intra-hepatic and extra-hepatic biliary ducts. We used the trans-esophagus (TE) and trans-jejunum (TJ) routes. In the present study, the utility of EUS-RV for biliary access was evaluated, focusing on the approach routes. Methods and Patients In 39 patients, 42 puncture routes were evaluated in detail. EUS-RV was performed between January 2010 and December 2014. The patients were prospectively enrolled, and their clinical data were retrospectively collected. Results The patients' median age was 71 (range 29-84) years. The indications for endoscopic retrograde cholangiopancreatography (ERCP) were malignant biliary obstruction in 24 patients and benign biliary disease in 15. The technical success rate was 78.6% (33/42) and was similar among approach routes (p=0.377). The overall complication rate was 16.7% (7/42) and was similar among approach routes (p=0.489). However, mediastinal emphysema occurred in 2 TE route EUS-RV patients. No EUS-RV-related deaths occurred. Conclusion EUS-RV proved reliable after failed ERCP. The selection of the appropriate route based on the patient's condition is crucial.

We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1-20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.

Patient: Female, 40 Final Diagnosis: Invasive ductal carcinoma arising in mucinous cystic neoplasm of pancreas Symptoms: None Medication: — Clinical Procedure: Surgical resection Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. Case Report: A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. Conclusions: We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinico-pathological parameter.

Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC.We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed.Median overall survival (OS) was significantly shorter for patients with high CEA (5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40).The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.

Background There have been no reports showing the incidence of anastomotic stenosis of continuous hepaticojejunostomy (HJ) and identifying its risk factors for patients who underwent pancreaticoduodenectomy (PD). Method We retrospectively investigated 200 patients whose HJ was established by unified method, single layered continuous suture. HJ stenosis was diagnosed with endoscopic or radiologic examinations. Uni and multivariable unconditional logistic modeling were performed to explore the predictive factors and to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Sixteen patients (8.0%) were diagnosed as HJ stenosis. Multivariable analysis showed that body mass index (BMI) (OR: 1.24; 95% CI: 1.03–1.51), absence of preoperative biliary stenting (OR: 11.10; 95% CI: 1.22–101.12), operative time (OR: 1.74 per one hour increase; 95% CI: 1.01–2.98), age (OR: 1.58 per 10 years increase; 95% CI: 0.88–2.85), and absence of nodal metastasis (OR: 3.43; 95% CI: 0.90–13.12) correlated with HJ stenosis. Among these, BMI and preoperative biliary stenting were associated with stenosis with a lower P-value than the others (P = 0.026 and 0.033, respectively). Conclusions The incidence of HJ stenosis was 8.0%. Close attention would be needed especially for patients at high risk of HJ stenosis, such as high BMI or absence of preoperative biliary stenting.

Background and study aims: Endoscopic resection is one treatment option for residual or locally recurrent esophageal cancer after definitive chemoradiotherapy or radiotherapy alone. However, little is known about the clinical benefit of salvage endoscopic resection for these lesions. Therefore, the effectiveness and prognostic factors of salvage endoscopic resection were investigated. Patients and methods: A total of 37 patients with esophageal squamous cell carcinoma (SCC) who underwent salvage endoscopic resection after definitive chemoradiotherapy or radiotherapy alone were reviewed. The method of salvage endoscopic resection was endoscopic mucosal resection using a cap (EMR-C), strip biopsy, or endoscopic submucosal dissection. The effectiveness and prognostic factors of salvage endoscopic resection were retrospectively analyzed. Results: A total of 37 patients with 49 lesions underwent salvage endoscopic resection. Baseline clinical stages were I in 23 patients, II in 3 patients, III in 9 patients, and IV in 2 patients. The number of locoregional recurrences and residual lesions were 35 and 14, respectively. The curative en bloc resection rate was 53.1 % (26/49). The total incidence of complications was 18.9 % (7/37); all were successfully managed conservatively. The 3-year and 5-year overall survival rates were 72.9 % and 53.3 %, respectively, with a median follow-up period of 54 months. Baseline clinical T1 – 2 and N0 were significant factors for good prognosis in terms of overall survival on univariate analysis. Conclusions: Salvage endoscopic resection, especially EMR-C, is a safe and feasible procedure to control residual or recurrent superficial esophageal SCC after definitive chemoradiotherapy or radiotherapy alone. The present results showed that baseline clinical T1 – 2 and N0 before chemoradiotherapy or radiotherapy were significant prognostic factors.

Carbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC.A total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL.Median RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value.The present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.

Objective Some patients with malignant gastric outlet obstruction require combined biliary and gastroduodenal stenting (double stenting). However, biliary stent dysfunction can often disturb biliary route maintenance, thus making the optimal biliary stenting for these patients unclear. The present study was designed to assess the factors associated with the long-term maintenance of biliary drainage routes. Methods The clinical features and long-term outcomes were assessed in patients who underwent double stenting. Patients The outcomes were reviewed in 43 consecutive patients who successfully underwent endoscopic double stenting with metallic stents. Results An univariate analysis of all patients with biliary stent dysfunction showed the separate type of double stenting (two stents placed in a non-crossed position) to be the only predictive factor related to successful biliary re-intervention for stent dysfunction (odds ratio 73.67, p=0.001). A comparison of the clinical features in patients who underwent separate and cross (two stents placed in a crossed position) stenting showed the functional success rate to be higher for the separate (93.3%) than for the cross (61.5%) stent type, with the median times to biliary stent dysfunction differing significantly (330 vs. 298 days, respectively; p=0.048). The success rates of re-intervention in patients with separate and cross type stents were 88.9% and 0.0%, respectively (p=0.001), and the initial biliary route maintenance rates were 96.7% and 53.8%, respectively (p=0.002). Conclusion The separate type of double stenting may enhance successful biliary re-intervention for stent dysfunction and also maintain the initial drainage route longer. The biliary drainage outcomes should therefore be considered when choosing the type of double stenting.