Comparative evaluation of new and conventional classifications of magnifying endoscopy with narrow band imaging for invasion depth of superficial esophageal squamous cell 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.

Prospective evaluation of a transnasal endoscopy utilizing flexible spectral imaging color enhancement (FICE) with the Valsalva maneuver for detecting pharyngeal and esophageal cancer.

BACKGROUND/AIMS: This study evaluated the efficacy and safety of transnasal endoscopy (TNE) with flexible spectral imaging color enhancement (FICE) for detection of superficial cancer in the pharyngeal and esophageal regions for high-risk populations. METHODOLOGY: Patients who previously had head and neck or esophageal squamous cell carcinoma were enrolled. Screening was conducted using TNE with conventional white-light endoscopy (WLE) followed by FICE chromoendoscopy. For observation of the pharyngeal region, the Valsalva maneuver was employed. RESULTS: 99 patients were eligible. Six esophageal cancers were detected in four patients (4.0%). The sensitivity, specificity, and accuracy for the detection of cancer were 25.0% (95% CI, 3.4- 71.0), 97.8% (95% CI, 92.1-99.8), and 94.9 % (95% CI, 88.4-98.1), respectively for WLE; 100% (95% CI, 45.4%- 100%), 96.8% (95% CI, 90.7%-99.3%), and 96.9% (95% CI, 89.3%-99.1%), respectively for FICE chromoendoscopy. Pain in the nose and nasal hemorrhage were observed in 3 (3.0%) and 2 patients (2.0%), respectively. Following the Valsalva maneuver, endoscopic scores significantly increased from a mean of 1.1 (0.8-1.4) to 2.0 (1.3-2.6) (p<0.05). CONCLUSIONS: TNE with the Valsalva maneuver is a promising screening method for the pharyngeal and esophageal regions. TNE with FICE chromoendoscopy for detecting pharyngeal and esophageal cancer was more sensitive than WLE.

Prospective clinical study of endoscopic ultrasound-guided choledochoduodenostomy with direct metallic stent placement using a forward-viewing echoendoscope.

A prospective clinical study was conducted to evaluate the safety, feasibility, and efficacy of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with direct metallic stent placement using a prototype forward-viewing echoendoscope. The indication for EUS - CDS in this study was lower biliary obstruction only, and not failed endoscopic biliary drainage, because the aim was to evaluate EUS - CDS for first-line biliary drainage therapy. The technical and functional success rates were 94 % (17 /18) and 94 % (16 /17), respectively. Early complications (focal peritonitis) were encountered in two patients (11 %). No patients developed late complications. EUS - CDS with direct metallic stent placement using a forward-viewing echoendoscope was generally feasible and effective for malignant distal biliary tract obstruction. The forward-viewing echoendoscope was useful, especially for deploying the metallic stent.

Endoscopic ultrasound-guided celiac ganglia neurolysis vs. celiac plexus neurolysis: a randomized multicenter trial.

BACKGROUND AND STUDY AIMS: No prospective comparison of endoscopic ultrasonography-guided direct celiac ganglia neurolysis (EUS - CGN) vs. EUS-guided celiac plexus neurolysis (EUS - CPN) has been reported. The aim of the current study was to compare the effectiveness of EUS - CGN and EUS - CPN in providing pain relief from upper abdominal cancer pain in a multicenter randomized controlled trial. PATIENTS AND METHODS: Patients with upper abdominal cancer pain were randomly assigned to treatment using either EUS - CGN or EUS - CPN. Evaluation was performed at Day 7 postoperatively using a pain scale of 0 to 10. Patients for whom pain decreased to ≤ 3 were considered to have a positive response, and those experiencing a decrease in pain to ≤ 1 were considered to be completely responsive. Comparison between the two groups was performed using intention-to-treat analysis. The primary endpoint was the difference in treatment response rates between EUS - CGN and EUS - CPN at postoperative Day 7. Secondary endpoints included differences in complete response rates, pain scores, duration of pain relief, and incidence of adverse effects. RESULTS: A total of 34 patients were assigned to each group. Visualization of ganglia was possible in 30 cases (88 %) in the EUS - CGN group. The positive response rate was significantly higher in the EUS - CGN group (73.5 %) than in the EUS - CPN group (45.5 %; P = 0.026). The complete response rate was also significantly higher in the EUS - CGN group (50.0 %) than in the EUS - CPN group (18.2 %; P = 0.010). There was no difference in adverse events or duration of pain relief between the two groups. CONCLUSIONS: EUS - CGN is significantly superior to conventional EUS - CPN in cancer pain relief. CLINICAL TRIAL REGISTRATION: http://www.umin.ac.jp/ctr/index.htm (ID: UMIN-000002536).

Role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration in diagnosing metastasis to the pancreas: a tertiary center experience.

BACKGROUND: Metastasis to the pancreas (MP) is a rare entity that is difficult to identify by imaging alone. Few reports have described endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) findings. Herein, we try to describe the EUS and EUS-FNA characteristics of MP. METHODS: This retrospective study compared 28 patients with MP (13 males; mean age: 60.1 ± 12.6 years) and 60 control patients (30 males; 62.7 ± 11.5 years) with pancreatic ductal adenocarcinoma (PDAC). All lesions were characterized by EUS, and MP was diagnosed by EUS-FNA (n = 16), surgery (n = 6) or both (n = 6). RESULTS: Multivariate logistic regression revealed that the presence of regular borders (p = 0.004; OR: 8.81, 95% CI: 1.97-39.4), the absence of retention cysts (p = 0.045; OR: 12.5, 95% CI: 1.06-147.0), and the absence of main pancreatic duct (MPD) dilation (p = 0.003; OR: 8.18, 95% CI: 2.04-32.8) were predictors of MP rather than PDAC. The EUS-FNA sampling adequacy was 95.4% (21/22), and the correct diagnosis was obtained in 95.2% (20/21) of cases when K-ras mutation analysis and/or immunostaining were added. CONCLUSION: The presence of regular borders, the absence of retention cysts and the presence of nondilated MPD on EUS indicate MP rather than PDAC. This diagnosis can be accurately confirmed by EUS-FNA with immunostaining and/or K-ras analysis.

Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms.

BACKGROUND AND STUDY AIMS: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs), and associated synchronous and metachronous pancreatic cancers are increasingly detected as imaging modalities become more sensitive. We investigated the natural history of SB-IPMN, and the incidence and characteristics of pancreatic cancers among patients undergoing long-term follow-up. PATIENTS AND METHODS: We reviewed the clinical, imaging, and pathological features in 103 patients, diagnosed at the Aichi Cancer Center between September 1988 and September 2006 as having SB-IPMN, and conservatively followed up for ≥ 2 years (median 59 months) based on an endoscopic ultrasonography (EUS) database. RESULTS: 74 (71.8 %) patients had nonprogressive lesions. Overall, six patients (5.8 %) developed pancreatic cancers during follow-up, with intraductal papillary mucinous (IPM) carcinoma in four, and ductal carcinoma of pancreas that was not IPMN in two patients. Of the six pancreatic cancers, five were diagnosed at a resectable stage. The 5-year and 10-year actuarial rates of development of pancreatic cancer were 2.4 % and 20.0 %, respectively. Although, at the last follow-up, cyst size, main pancreatic duct (MPD) diameter, mural nodule size, and frequency of metachronous and/or synchronous cancers of other organs were significantly higher in patients who developed IPM carcinoma, resected SB-IPMNs without mural nodules and dilated MPDs had no IPM carcinomas. CONCLUSIONS: The frequency of pancreatic cancers is high on long-term follow-up of SB-IPMN. Although conservative management is appropriate for selected patients, regular and long-term imaging, especially by EUS is essential, even if SB-IPMN remains unchanged for 2 years. Presence of mural nodule and dilated MPD seem to be more appropriate indicators for resection than cyst size alone for SB-IPMNs.

EUS-guided choledochoduodenostomy for palliative biliary drainage in patients with malignant biliary obstruction: results of long-term follow-up.

Five patients with obstructive jaundice caused by malignant periampullary biliary stenosis underwent EUS-guided choledochoduodenostomy (EUS-CDS) from the first portion of the duodenum using a convex echoendoscope and a needle knife. All the steps of the procedure including passage dilatation and the plastic stent placement were performed through the accessory channel of the echoendoscope over the guide wire. Stent insertion was technically successful in all five patients. The procedure was also clinically effective in relieving jaundice in all cases. One patient developed pneumoperitoneum, which resolved with conservative management. Stent exchange was successful in seven of eight attempts in patients with stent occlusion. One failure was due to tumor invasion to the choledochoduodenal fistula. Stent patency was maintained in the remaining patients throughout their survival period. The average stent patency was 211.8 days. EUS-CDS from the first portion of the duodenum appears to be feasible and safe in cases of obstructive jaundice caused by distal bile duct obstruction.

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer.

PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection.

BACKGROUND: Some, but not all studies have provided evidence that the CagA status of Helicobacter pylori strains is a predictive factor for the outcome of eradication therapy. AIM: To clarify the association between CagA status and eradication outcome. METHODS: We included studies reporting the numbers of successful and failed cases in H. pylori-eradication therapy according to the CagA status. Fourteen studies (1529 patients) were included of 325 articles identified in the search. The pooled risk ratio for H. pylori-eradication failure in CagA-negative relative to CagA-positive strains and the pooled risk difference in eradication success between the two groups were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: The summary risk ratio for eradication failure in CagA-negative relative to CagA-positive was 2.0 (95% CI: 1.6-2.4, P < 0.001), corresponding with the summary risk difference for eradication success between the groups of 11% (95% CI: 3-19%, P = 0.011). Meta-regression analysis demonstrated that usage of polymerase chain reaction examination for CagA status and a high proportion of non-ulcer dyspepsia patients were factors for heterogeneity among studies. CONCLUSIONS: Our meta-analysis confirmed the importance of the presence of CagA as a predictor for successful eradication of H. pylori.

Methylation status of the p15INK4B gene in hematopoietic progenitors and peripheral blood cells in myelodysplastic syndromes.

We previously reported that the hypermethylation of the p15INK4B gene promoter was frequently observed in myelodysplastic syndromes (MDS), and that it may be associated with disease progression. An unanswered question is whether p15INK4B gene methylation is restricted to undifferentiated blastic cells, or whether differentiated cells such as granulocytes or erythrocytes of MDS origin also harbor this epigenetic alteration. In this study, we analyzed the methylation status of the p15INK4B gene in MDS by the methylation-specific PCR (MSP) method, which is more sensitive than Southern blotting. The bone marrow mononuclear cells (BM-MNCs) of 23 MDS patients were analyzed, and six of them showed p15INK4B methylation. Progenitor assay with methylcellulose medium was also performed in all patients. In two of the six patients with p15INK4B-methylated BM-MNCs, erythroid and/or non-erythroid colonies formed were subjected to molecular analysis. Colonies with and without p15INK4B methylation were detected in both patients. Furthermore, X-chromosome inactivation (XCI) pattern of each colony was simultaneously determined by MSP-based human androgen receptor gene analysis (HUMARA-MSP), and all p15INK4B-methylated colonies showed the same XCI pattern, which was dominant among the colonies, while p15INK4B-unmethylated colonies showed both patterns of XCI, in each of the two patients. We then examined the methylation status of the p15INK4B gene of granulocyte (PB-PMN) fractions from 10 patients with available peripheral blood cells. In all four patients with p15INK4B-methylated BM-MNCs, their PB-PMNs showed p15INK4B methylation. These results suggest that p15INK4B methylation in hematopoietic cells in MDS patients is restricted to the MDS clone but not necessarily to blast cells.

Peripheral T/natural killer-cell lymphoma involving the female genital tract: a clinicopathologic study of 5 cases.

Malignant lymphoma of the female genital tract (FGT) is rare. In this study, 5 peripheral T/natural killer (NK)-cell lymphomas (PTCLs) involving the FGT are reported. They include 2 from the uterus and 1 each from ovary, uterus and ovary, and vagina, and were detected between 1996 and 2000. One of the 2 ovarian tumors was bilateral. In all cases, the FGT was the initial site of clinical presentation of disease. Age at presentation ranged from 21 to 52 years (median, 36 years). One case was stage I disease, 2 were stage II, and 2 were stage IV. All 5 tumors were positive for CD3epsilon, and 3 harbored the Epstein-Barr virus, although the detailed immunophenotypic profiles varied. Three were diagnosed as nasal type T/NK-cell lymphoma, 1 as anaplastic large-cell lymphoma (anaplastic lymphoma kinase [ALK]-positive), and 1 as unspecified PTCL of cytotoxic phenotype, according to the forthcoming World Health Organization classification. Four of 5 patients received laparotomy and chemotherapy. Four patients (in stages II and IV) died of disease within 16 months of the initial diagnosis, whereas only 1 patient (in stage I) is alive without disease at 39 months of follow-up. Our experience in this series provided clinically relevant information on diagnosis, treatment, and outcome for extremely rare tumors of the FGT.

Analysis of microsatellite instability, TGF-beta type II receptor gene mutations and hMSH2 and hMLH1 allele losses in pancreaticobiliary maljunction-associated biliary tract tumors.

While pancreaticobiliary maljunctions (PBM) are clearly associated with biliary tract tumor development, little is known about their molecular mechanisms. This study was conducted to assess the contributions of microsatellite instability (MSI), mutations of transforming growth factor type II receptor (TGF-beta RII) and insulin-like growth factor type II receptor (IGF RII) genes and loss of heterozygosity (LOH) of hMSH2 and hMLH1 in 23 biliary tract tumors using PCR methods. MSI was detected by 13 markers in 16/23 samples (69.6%). TGF-beta RII mutations were detected in eight of these (50%), and of the IGF IIR gene in two (12.5%). LOH was detected in 4/16 (25%) at the hMSH2 locus, and 2/16 (12.5%) at the hMLH1 locus. No TGF-beta RII mutations or LOH of hMSH2 and hMLH1 were detected in MSI-negative samples. These findings suggest that MSI plays an important role in carcinogenesis of the biliary tract epithelium with PBM cases.