No effective early diagnostic biomarkers are available for colorectal cancer (CRC). Therefore, we sought to identify new biomarkers that could identify CRC from progression as a pre-cancerous lesion to its invasive form. Recent studies have shown that microRNAs (miRs) are associated with the onset of cancer invasion and progression.
We hypothesized that the identification of miRs associated with CRC might be useful to detect this disease at early stages.
We conducted an integrated analysis of 79 isolated colorectal tumor glands, including adenomas, intramucosal cancers, and invasive CRCs that showed a microsatellite stable phenotype using GeneChip miRNA 4.0 microarray assays. The colorectal tumors we examined were divided into 2 cohorts (42 in the first cohort and 37 in the second cohort).
First, cluster analysis was performed to stratify expression patterns of multiple miRs that were pooled according to the following criteria: fold change in expression (< -2.0 or > 2.0), p < 0.05, and mature miRs. As a result, the expression patterns of pooled miRs were subdivided into 3 subgroups that were correlated with tumor grade. Each subgroup was characterized by specific miRs. In addition, we found that specific miRs, including miR-140-3p and miR-378i, were closely associated with cancer invasion. Finally, we analyzed paired dysregulated miRs between adenomatous and cancerous components present within the same tumor.
We showed that several miRs were dysregulated during progression from adenoma to intramucosal cancer. Specific miRs may have key roles in progression from intramucosal tumor to invasive CRC.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a very rare variant of alpha-fetoprotein-producing gastric cancer (AFPGC). GAED is histologically characterized by cuboidal or columnar cells, which resemble those found in the primitive gut and have clear cytoplasm. In previously reported cases, GAED exhibit more aggressive behavior, as well as AFPGC, than conventional gastric cancer, such as marked lymphovascular invasion, lymph node metastasis, and liver metastasis. And also GAED was usually located in a deep mucosal layer and was covered by a conventional adenocarcinoma (CA) component. Based on these findings, GAED is considered to develop from CA during the process of tumor invasion and proliferation. We present a very rare case of early-stage GAED achieved curatively resected via endoscopic submucosal dissection, in which the lesion was composed of a pure enteroblastic differentiation component without a CA component.

The diagnostic depth of photodynamic diagnosis (PDD) for gastric cancer with protoporphyrin IX (PpIX) is limited, which leads to missing intramucosal cancers in screening and surgery.
The reason is that the excitation light, whose wavelength is determined by the highest absorption peak of PpIX (∼405  nm), is strongly attenuated by mucosal tissues. We investigated an excitation wavelength that can extend the diagnostic depth of PpIX fluorescence at the mucosal subsurface.
By calculating the depth-dependent intensity of the excitation light in porcine gastric mucosa for each wavelength, relationships among the wavelength, fluorophore depth, and fluorescence intensity were assessed and fluorescence images of PpIX pellets located at different fluorophore depths were compared experimentally by changing the excitation wavelength.
The numerical calculation showed that a 505-nm excitation light provided the highest fluorescence intensities at a fluorophore depth deeper than 1.1 mm. In the fluorescence observation, the fluorescence intensities at fluorophore depths of 0 and 1.0 mm at 405 nm were 5.4  ×  103 and 1.0  ×  103  arb. units, whereas those at 505 nm were 5.3  ×  101 and 1.9  ×  102  arb. units, respectively.
The experimental results suggest that the diagnosis depth of PDD with PpIX for intramucosal cancer can be extended by 505-nm excitation light.

Barrett\'s esophagus with high-grade dysplasia and early-stage adenocarcinoma is amenable to curative treatment by endoscopic resection. Histopathological correlation has established that mucosal cancer has minimal risk of nodal metastases and that long-term complete remission can be achieved. Although surgery is the gold-standard treatment once there is submucosal involvement, even T1sm1 (submucosal invasion ≤ 500 μm) cases without additional risk factors for nodal metastases might also be cured with endoscopic resection. Endoscopic resection is foremost an initial diagnostic procedure, and once histopathological assessment confirms that curative criteria are met, it will be considered curative. Endoscopic resection may be achieved by endoscopic mucosal resection, which, although easy to perform with relatively low risk, is limited by an inability to achieve en bloc resection for lesions of size more than 1.5 cm. Conversely, the technique of endoscopic submucosal dissection is more technically demanding with higher risk of complications but is able to achieve en bloc resection for lesions larger than 1.5 cm. Endoscopic submucosal dissection would be particularly important in specific situations such as suspected submucosal invasion and lesion size more than 1.5 cm. In other situations, since endoscopic resection would always be combined with radiofrequency ablation to ablate the remaining Barrett\'s epithelium, piecemeal endoscopic mucosal resection would suffice since any remnant superficial invisible dysplasia would be ablated.

BACKGROUND: Early reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time.
METHODS: All consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow-up data were recorded. The results obtained over three years were compared to previously published data covering the 2008-2010 period.
RESULTS: Between November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010-2013 vs 32.1 ± 21 for 2008-2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No procedure-related mortality was recorded.
CONCLUSIONS: In this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.

In recent years, a number of endoluminal procedures such as endoscopic resection and thermal ablation have emerged as less invasive treatment options for early esophageal cancer. These therapies have demonstrated excellent oncologic outcomes for dysplasia as well as intramucosal cancers. However, few studies have directly compared long-term outcomes of endoscopic therapy versus traditional esophagectomy. Current esophagectomy techniques now deliver consistently good outcomes in the hands of experienced surgeons at high volume centers, and this option should be considered an important treatment consideration for early esophageal cancer. Under current recommendations, esophagectomy should be considered for tumors invading the submucosa, tumors with high-risk pathologic features, bulky tumors, multinodular tumors, tumors within a long segment of Barrett\'s esophagus, and tumors adjacent to a hiatal hernia. Likewise, individual patient factors and comorbidities must also be considered when determining the best treatment for a patient with early esophageal cancer. The risk of missing metastatic disease or recurrence that is associated with endoscopic treatment must be weighed against the surgical risks of esophagectomy. With these considerations in mind, the aim of this article is to review the current guidelines and literature that explore the role of esophagectomy for early esophageal malignancy in the era of endoscopic therapies.

OBJECTIVE: Accurate estimation of lymph node metastasis (LNM) in intramucosal gastric cancer is essential to select less invasive treatment options and even avoid surgery. The aim of this study was to evaluate combined clinicopathological features to predict the presence of LNM.
METHODS: A retrospective review of data from 386 intramucosal gastric cancer patients who underwent gastrectomy with extended lymphadenectomy from 2003 to 2010 was conducted. The mutual relation between clinicopathological characteristics and LNM was analyzed.
RESULTS: LNM was detected in 40 (10.4%) of the 386 patients. Histological type and vascular or lymphatic invasion presence showed a positive correlation with LNM occurrence by univariate analysis. Multivariate analysis revealed that histological type was the only factor associated with LNM. Combined clinicopathologic characteristics would be more predictable for LNM. We found no LNM when we used combined clinicopathological characteristics conforming to Japanese absolute indications for endoscopic therapy. The LNM rate was as high as 8.7% when Japanese expanded criteria were used. Univariate analysis in cancer conformity to expand endoscopic submucosal dissection (ESD) indication also revealed that the undifferential type was the only significant factor for LNM.
CONCLUSIONS: It was possible to predict intramucosal gastric cancer cases without LNM using combined clinicopathological characteristic analysis. Extended indication for ESD should be cautiously used for intramucosal gastric cancer patients.

Patients with Barrett\'s esophagus (BE) and high-grade dysplasia (HGD) or intramucosal cancer (IMC) on endoscopic forceps biopsies are referred to endoscopic therapy even though forceps biopsies do not reflect the disease extent accurately. Endoscopic mucosal resection (EMR) and endoscopic ultrasound (EUS) are frequently used for staging prior to endoscopic therapy. Our aims were to evaluate: (1) if endoscopic forceps biopsies correlated with EMR histology in these patients; (2) the utility of EUS compared to EMR; and (3) if accuracy of EUS varied based on grade of differentiation of tumor.
This is a retrospective review of patients referred to endoscopic therapy of BE with HGD or early esophageal adenocarcinoma (EAC) who underwent EMR from 2006 to 2011. Age, race, sex, length of Barrett\'s segment, hiatal hernia size, number of endoscopies and biopsy results and EUS findings were abstracted.
A total of 151 patients underwent EMR. In 50 % (75/151) of patients, EMR histology was consistent with endoscopic forceps biopsy findings. EMR resulted in change in diagnosis with upstaging in 21 % (32/151) and downstaging in 29 % (44/151). In patients with HGD on EMR, EUS staging was T0 in 74.1 % (23/31) but upstaged in 25.8 % (8/31). In patients with IMC on EMR, EUS findings were T1a in 23.6 % (9/38), upstaged in 18.4 % (7/38) and downstaged in 57.8 % (22/38). EUS accurately identified EMR histology in all submucosal cancers. Grade of differentiation was reported in 24 cancers on EMR histology. There was no correlation between grade and EUS staging.
EUS is of limited utility in accurate staging of BE patients with HGD or early EAC. Endoscopic forceps biopsy correlated with EMR findings in only 50 % of patients. Irrespective of the endoscopic forceps biopsy results, all BE patients with visible lesions should be referred to EMR.

OBJECTIVE: To examine the efficacy of non-magnifying narrow-band imaging (NM-NBI) imaging for small signet ring cell carcinoma (SRC).
METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection (ESD) and 14 randomly selected whitish gastric ulcer scars (control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging (WLI) were assessed with Image J (NIH, Bethesda).
RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index (P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle (C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs (P = 0.001). According to the receiver-operating characteristic analysis, the resulting cut-off value of the circularity index (C-index) for SRC was 0.60 (85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar (OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).
CONCLUSIONS: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

Endoscopic mucosal resection (EMR) has become the standard treatment for early oesophageal neoplasia. The mucosal defect caused by EMR usually takes several weeks to heal. Despite guidelines on high-risk endoscopic procedures in patients on anticoagulation, evidence is lacking whether EMR is safe in such patients. We investigated the immediate and delayed bleeding risk in patients undergoing diagnostic or therapeutic oesophageal EMR comparing patients requiring warfarin anticoagulation with a control group.
Warfarin was stopped 5 days before the planned EMR and restarted on the evening following the procedure. Patients with high-risk conditions, such as recent pulmonary thromboemboli, received bridging with low molecular weight heparin. All EMRs were performed when the INR was <1.5. Bleeding events on the day of the EMR and within 3 months post-procedure were documented.
One hundred and seventeen consecutive patients with early oesophageal neoplasia were included. Sixty-eight EMRs were performed in 15 patients requiring anticoagulation. One patient on warfarin was readmitted 10 days after EMR with haematemesis and melaena. Out of 400 EMRs in 102 controls, 26 immediate bleeding events occurred requiring endoscopic intervention. One delayed bleeding event (melaena) occurred in the control group. The number of bleeding events did not differ between groups [p = 0.99; odds ratio 1.01 (0.30-3.44)], neither for acute (p = 0.76) nor delayed bleeding (p = 0.24).
EMR of early oesophageal neoplasia can be safely performed in patients requiring anticoagulation when warfarin is discontinued 5 days before the endoscopic intervention and reinstituted on the evening of the procedure day.