The safety and feasibility of endoscopic submucosal dissection using a flexible three-dimensional endoscope for early gastric cancer and superficial esophageal cancer: A prospective observational study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is performed as one of standard treatments for patients with early gastric cancer (EGC) and superficial esophageal squamous cancer (SESCC). A prototype of a flexible endoscope with a 3-D system has been recently developed. This study aimed to investigate the safety and feasibility of ESD using a 3-D flexible endoscope (3-D ESD) for EGC and SESCC. METHODS: This single-center, prospective, observational study enrolled patients who underwent planned 3-D ESD. The clinical outcomes, including the incidence of adverse events and treatment results, were analyzed. Visibility and manipulation during 3-D ESD were evaluated using a visual analog scale (VAS). We also evaluated the effect of the 3-D system on the endoscopist using VAS and the critical flicker fusion frequency (CFFF). RESULTS: We analyzed 47 EGC and 20 SESCC cases. There are no bleeding cases that required transfusion and perforation during 3-D ESD in both EGC and SESCC patients. However, the incidence of delayed bleeding and delayed perforation was 1.5% (one case) each. The mean VAS scores for recognizing the submucosal layer during the submucosal dissection, visual perception of blood vessel, and depth perception were 72.7 ± 22.2, 74.7 ± 21.8, and 78.2 ± 19.9, respectively. In contrast, the mean VAS score for manipulation was 25.4 ± 19.7. Among endoscopists, there was no significant difference in the VAS of eyestrain and headache before and after ESD, and there was no significant difference in the CFFF. CONCLUSION: The safety and feasibility of 3-D ESD for EGC and SESCC are acceptable in both patients and endoscopists.

Safety of endoscopic procedures with monopolar versus bipolar instruments in an ex vivo porcine model.

BACKGROUND: Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model. METHODS: We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations. RESULTS: Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used. CONCLUSIONS: Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.

Advantages of salvage photodynamic therapy using talaporfin sodium for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.

BACKGROUND: Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT). METHODS: We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled. RESULTS: A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]). CONCLUSIONS: L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.

Endoscopic prediction of advanced histology in colorectal lesions sized <10 mm using the Japan Narrow-band imaging Expert Team classification.

BACKGROUND AND AIM: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm. METHODS: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions. RESULTS: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors. CONCLUSION: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm.

Prophylactic steroid administration against strictures is not enough for mucosal defects involving the entire circumference of the esophageal lumen after esophageal endoscopic submucosal dissection (ESD).

BACKGROUNDS: The width of mucosal defects after endoscopic submucosal dissection (ESD) of esophageal squamous cell carcinoma (ESCC) is known to be a risk factor for esophageal strictures. Although steroid injection and oral steroid have recently been reported as prophylactic treatments, these were shown to be ineffective in a subset of patients with post-ESD mucosal defects involving the entire circumference of the esophagus. The aim of this study was to demonstrate outcome with prophylactic steroid administration for post-ESD mucosal defects involving the entire circumference, and to explore risk factors for esophageal strictures except for circumference of the esophagus. METHODS: Between November 2012 and August 2018, we enrolled patients with post-ESD mucosal defects involving the entire circumference of the esophagus who had received steroid injection (triamcinolone acetonide 50-100 mg, given immediately after ESD) followed by oral steroid (prednisolone 30 mg/day, tapered gradually over 8 weeks) as prophylactic treatment. Esophageal stricture was defined as case where ordinary-sized endoscope could not pass through post-ESD site, thus requiring endoscopic balloon dilation (EBD) repeatedly until relief of stricture was achieved. We retrospectively evaluated the rates of strictures, refractory strictures (requiring ≥ 6 EBD procedures) and unimproved strictures (not improvable by repeated EBD alone) and explored risk factors for strictures. RESULTS: A total of 26 patients met the including criteria. The rates of strictures, refractory strictures, and unimproved strictures were 62%, 38%, and 12%, respectively. The pre-ESD longitudinal extension of the lesion > 5 cm was identified as a risk factor for refractory strictures, suggesting that lesions with this factor had a shorter time to stricture development, required more EBD procedures, and longer EBD durations. CONCLUSION: Although additional study is required in a larger number of patients, careful consideration needs to be given to ESD as an indication for large spreading ESCC involving the entire circumference of esophagus given its high stricture risk.

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence.

BACKGROUND: Proton beam therapy (PBT) with concurrent chemotherapy is promising for esophageal squamous cell carcinoma (ESCC). The aim of study was to evaluate the outcome of concurrent chemo-proton therapy (CCPT), i.e., PBT with concurrent chemotherapy for cT1 ESCC and the salvage endoscopic therapy for local recurrence. METHODS: Patients with clinical T1 ESCC who underwent CCPT (60 GyE) between April 2013 and April 2017 at the National Cancer Center Hospital East were investigated. The efficacy of CCPT at the primary site was evaluated via endoscopy; primary complete response (CR) was defined as disappearance of the tumor lesion/ulcer and absence of cancer cells on biopsy. Endoscopic evaluation was performed with the same protocol of conventional chemoradiotherapy. Local recurrence after CCPT was treated with endoscopic resection for cT1a and with esophagectomy or photodynamic therapy for cT1b+. RESULTS: Of the 44 patients (median age, 70 years) that underwent CCPT, 43 patients (98%) achieved primary CR. Among the 44 patients, the 3-year overall survival rate was 95.2%. Five patients (11%) developed local recurrence without regional lymph node or distant metastasis and received endoscopic resection or photodynamic therapy. All five patients were alive with no recurrence after a median 23 months. CONCLUSIONS: The results suggest that CCPT is an effective treatment for cT1 ESCC and careful endoscopic follow-up allows preferable local control with salvage endoscopic treatment.

Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and mesenchymal epithelial transition factor-positive sites of gastric cancer using surgical samples.

BACKGROUND: Receptor tyrosine kinases (RTKs) play critical roles in gastric cancer (GC) progression and are potential targets for novel molecular-targeted agents or photo-immunotherapies. During patient selection, targeted biopsy is the first step. However, heterogeneous expression of RTKs based on the macroscopic appearance in GC has not been extensively addressed. Accordingly, in this study, we evaluated differences in RTK expression associated with macroscopic appearance in GC. METHODS: In total, 375 consecutive patients who had undergone gastrectomy at the National Cancer Center Hospital East and who had histologically proven adenocarcinoma, available archived tumor sample, and no history of chemotherapy were enrolled in this study. For these cases, tissue microarray (TMA) samples were examined using immunohistochemistry (IHC). Based on the results of IHC, cases were selected for detailed examination. We re-evaluated IHC scores in more than three tumor blocks per case and comparatively evaluated differences in IHC expression in RTKs between the mucosal portion (MuP) and invasive portion (InP). RESULTS: Human epidermal growth factor receptor 2 (HER2)-, epidermal growth factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)-positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then analyzed to assess differences in IHC expression levels in the same lesion. Concordance rates of positive staining of HER2, EGFR, and MET between MuP and whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%. CONCLUSIONS: To avoid underestimating expression status, biopsies must be taken from MuP for HER2, InP for EGFR, and both proportions for c-MET.

Endoscopic submucosal resection using a ligation device without injection for duodenal neuroendocrine tumors.

BACKGROUND: Duodenal neuroendocrine tumors (NETs) measuring ≤ 10 mm in diameter that are confined to the submucosal layer without metastasis are suitable for endoscopic treatment. We previously reported the efficacy and safety of endoscopic submucosal resection with a ligation device (ESMR-L) for duodenal NETs. In order to make the procedure simpler, we attempted ESMR-L without submucosal injection. The aim of this study was to evaluate the efficacy of ESMR-L without injection for duodenal NETs. METHODS: A total of 12 patients with small (≤ 10 mm) sporadic duodenal NETs were treated via endoscopic resection at the National Cancer Center Hospital East between December 2010 and May 2018. All patients were evaluated via endoscopy and endoscopic ultrasound, and abdominal computed tomography was performed to rule out metastatic lesions. The patients' characteristics, clinical courses, and complications, such as perforation and bleeding, were retrospectively assessed. We examined the correlation between ESMR-L with or without submucosal saline injection and clinicopathological parameters. RESULTS: The median procedural time for ESMR-L was 13 min. All lesions invaded the submucosal layer, and the histological diagnoses were classified as NET G1 in 11 lesions and NET G2 in one lesion. En bloc resection and complete resection were achieved in 12 and 11 lesions, respectively. The postoperative duration of hospital stay was 4 days. At the median follow-up of 17 months, there was no incidence of local recurrence or distant metastasis. Perforation and intraoperative bleeding were not observed. However, delayed bleeding was found in one patient. ESMR-L without submucosal injection required a significantly shorter procedural time than ESMR-L with submucosal saline injection (10 min vs. 15 min, respectively; p = 0.007). CONCLUSIONS: ESMR-L is safe and effective. Particularly, ESMR-L without submucosal injection could be used to treat these NETs safely within a short period of time.

Objective evaluation of the visibility of colorectal lesions using eye tracking.

BACKGROUND AND AIM: To assess the visibility of colorectal lesions using blue laser imaging (BLI)-bright and linked-color imaging (LCI) with an eye-tracking system. METHODS: Eleven endoscopists evaluated 90 images of 30 colorectal lesions. The lesions were randomly selected. Three images of each lesion comprised white light imaging (WLI), BLI-bright, and LCI in the same position. Participants gazed at the images, and their eye movements were tracked by the eye tracker. We analyzed whether the participants could detect the lesion and how long they took to detect the lesion. We assessed the miss rate and detection time among the imaging modalities. RESULTS: One endoscopist was excluded, and 10 endoscopists were assessed. Overall, 12.6% of lesions were missed with WLI, 6.0% with BLI-bright, and 4.3% with LCI; the miss rate of BLI-bright and LCI was significantly lower than that of WLI (P < 0.01), with no significant difference between the former modalities (P = 0.54). Mean (± SD) detection times were 1.58 ± 1.60 s for WLI, 1.01 ± 1.21 s for BLI-bright, and 1.10 ± 1.16 s for LCI. Detection time for BLI-bright and LCI was significantly shorter than that for WLI (P < 0.0001), with no significant difference between the former modalities (P = 0.34). Regarding the miss rate and detection time between the expert and the non-experts, there was a significant difference with WLI but not with BLI-bright and LCI. CONCLUSION: Blue laser imaging-bright and LCI improved the detection of colorectal lesions compared with WLI using an eye-tracking system.

Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion.

We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with the presence of WNT pathway gene alterations, all superficially serrated adenomas showed focal or diffuse nuclear ß-catenin accumulation. Since concurrent KRAS mutations and RSPO fusions are reportedly common in traditional serrated adenomas, we reviewed 129 traditional serrated adenomas and found 15 lesions (12%) that were associated with superficially serrated adenoma components. Remarkably, all but one superficially serrated adenoma-associated traditional serrated adenoma exhibited concurrent KRAS mutations and RSPO fusions/overexpression. The present study suggests that superficially serrated adenoma is a morphologically and molecularly distinct type of colorectal serrated polyp that is histogenetically related to traditional serrated adenoma.

Technical feasibility of endoscopic submucosal dissection for local failure after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Salvage endoscopic submucosal dissection (ESD) after chemoradiotherapy can be technically difficult as a result of radiation-induced fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) and for other primary lesions within the irradiation field. METHODS: Consecutive patients treated with ESD for superficial ESCC between December 2009 and May 2017 were investigated retrospectively and stratified into group A (33 patients, 35 lesions; local failure at the primary site after chemoradiotherapy), group B (25 patients, 34 lesions; second primary lesions within the irradiation field), and group C (550 patients, 596 lesions; radiotherapy-naïve superficial ESCC). We evaluated procedural success rate, en bloc resection rate, 1-year local relapse-free survival (LRFS) rate, procedure time, and incidence of major adverse events. RESULTS: The rates of procedural success and en bloc resection, respectively, were significantly lower in group A (89%, 86%) than in groups B (100%, 100%) and C (100%, 98%). The 1-year LRFS rates were 86%, 100%, and 99% in groups A, B, and C, respectively, and significantly lower in group A than in group C. Serious adverse events including perforation were not observed in groups A and B; perforation occurred only in group C (2.8%). CONCLUSIONS: ESD is technically feasible in patients with local failure, especially as initial salvage treatment and as treatment for second primary lesions within the irradiation field.

Pilot study on probe-based confocal laser endomicroscopy for colorectal neoplasms: an initial experience in Japan.

BACKGROUND: The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions. METHODS: Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor's depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor's features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review). RESULTS: A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27-1.0). CONCLUSIONS: pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.

Clinicopathological features and endoscopic findings of HER2-positive gastric cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) expression in gastric cancer is highly heterogeneous. Therefore, it is important to take endoscopic samples from appropriate tumor sites. METHODS: Between January 2008 and April 2015, patients with gastric or gastroesophageal junction cancer with histologically confirmed adenocarcinoma were included. Surgical samples or endoscopic biopsy samples were examined for HER2 using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tissues were considered to be HER2 positive when either assessment revealed either an IHC score of 3+ or an IHC score of 2+ accompanied by a positive FISH result. Endoscopic findings were retrieved in all cases where available, and we examined the portion from which a biopsy was obtained. RESULTS: Out of the 612 patients included in the study, 104 (17%) were HER2 positive. The proportion of HER2-positive gastric tumors with differentiated (vs. undifferentiated) histology was significantly higher (29 vs. 6%, respectively; p < 0.001). The HER2-positive rate of papillary adenocarcinomas (vs. tubular) was particularly high (62%, 8/13; p = 0.023). The proportion of HER2-positive gastric tumors of Borrmann classification 0 or 1 was significantly higher than that of tumors of classified as 2, 3, or 4 (45 vs. 16%, respectively; p < 0.001). The HER2-positive rates per biopsy specimen from the superficial spreading portion, ulcer mound, ulcer bed, and mass portion were 100, 91, 45, and 100%, respectively. CONCLUSIONS: HER2-positive gastric cancer tends to be associated with a differentiated histology, particularly papillary adenocarcinoma, and a Borrmann classification of 0 or 1 tumors. Based on these endoscopic findings, it is important to recognize the superficial spreading portion and the mass portion of gastric malignancies.

Salvage endoscopic resection (ER) after chemoradiotherapy for esophageal squamous cell carcinoma: What are the risk factors for recurrence after salvage ER?

BACKGROUND AND AIM: Salvage endoscopic resection (ER) is among the curative treatments for superficial local failure after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). The present study aimed to clarify risk factors for recurrence after salvage ER. METHODS: This study enrolled consecutive ESCC patients treated with salvage ER for local failure after CRT between 1998 and 2013. Recurrences after salvage ER included locoregional recurrences and distant metastases. Multivariate analysis was carried out on clinicopathological parameters to identify risk factors for post-salvage ER recurrence. RESULTS: Of the 72 patients enrolled in this study, 37/8/23/4 patients had been staged before CRT as cT1/T2/T3/T4 and 44/28 patients as cN0/N1, respectively, and local failures detected before salvage ER were residual lesions after CRT in 19 and local recurrences in 53 patients. Resected specimens were classified as pT1a (M) in 45 and pT1b (SM) in 27 patients. During the median 45-month follow up (range, 3-175 months) after salvage ER, 27 (38%) patients developed recurrence with a 3-year recurrence-free survival rate of 48.9% (95% confidence interval [CI], 36.5-60.3). Multivariate analysis showed that residual lesions after CRT (HR, 2.55; 95% CI, 1.32-4.94) and lesions with a submucosal tumor (SMT)-like appearance before salvage ER (HR, 2.08; 95% CI, 1.04-4.18) were significantly associated with post-salvage ER recurrence. CONCLUSIONS: Clinical findings (e.g. residual tumors found immediately after CRT and macroscopic SMT-like appearance before salvage ER) were shown to be significant risk factors for post-salvage ER recurrence.

Endoscopic treatment outcomes of laterally spreading tumors with a skirt (with video).

BACKGROUND AND AIMS: A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts. METHODS: Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection. RESULTS: Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P < .01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P = .032, and odds ratio, 12.3; P = .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence. CONCLUSIONS: LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence.

Clinicopathological, endoscopic, and molecular characteristics of the "skirt" - a new entity of lesions at the margin of laterally spreading tumors.

BACKGROUND AND STUDY AIM: A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt. PATIENTS AND METHODS: Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes. RESULTS: A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt. CONCLUSION: The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt.

Endoscopic submucosal resection with a ligation device for the treatment of duodenal neuroendocrine tumors.

BACKGROUND: Endoscopic submucosal resection with a ligation device (ESMR-L) is effective for rectal neuroendocrine tumors (NETs); however, its effectiveness for duodenal NETs is unclear. This study evaluated the efficacy and safety of ESMR-L for duodenal NETs. METHODS: A total of 32 consecutive patients with duodenal NETs were treated in our hospital between December 2010 and August 2015. Among these 32 patients, we retrospectively analyzed the data of all patients who underwent ESMR-L for the treatment of duodenal NETs. ESMR-L was considered for patients in whom (1) the lesion size was ≤10 mm in diameter, (2) the lesion was located within the submucosal layer, and (3) no lymph node metastasis or distant metastasis was detected. RESULTS: Five patients underwent ESMR-L for the treatment of duodenal NETs. The en bloc complete resection rate was 100 %. The median procedure time for ESMR-L was 15 min (range 10-30 min). In all patients, perforation during and after the operation, and intraoperative bleeding were not observed; however, one patient experienced postoperative bleeding. During follow-up, no local recurrence or distant metastasis was noted in any of the patients. CONCLUSION: ESMR-L is feasible, effective, and safe for duodenal NETs measuring ≤10 mm in diameter that are confined to the submucosal layer without metastasis.

Clinical outcome after endoscopic resection for superficial pharyngeal squamous cell carcinoma invading the subepithelial layer.

BACKGROUND AND STUDY AIMS: The curability of endoscopic resection for superficial pharyngeal squamous cell carcinoma (SPSCC) has not been fully elucidated, particularly for lesions invading the subepithelial layer, which carry the risk of metastasis. The aim of this study was to evaluate the curative potential of endoscopic resection for SPSCC invading the subepithelial layer. PATIENTS AND METHODS: From June 2002 to July 2010, 198 SPSCCs in 176 consecutive patients were treated by endoscopic resection at two tertiary referral centers. Selection criteria were initial endoscopic resection, histologically proven squamous cell carcinoma invading the subepithelial layer, no lymph node or distant metastasis before endoscopic resection, and no prior treatment for pharyngeal squamous cell carcinoma. Endoscopic resection was performed under general anesthesia. Long-term survival and clinical outcomes were retrospectively evaluated. RESULTS: Among 176 consecutive patients, 50 lesions in 47 patients (all male; median age 64 years) were histologically diagnosed from endoscopic resection specimens as having subepithelial invasion. Median tumor thickness was 1000 µm (range 200 - 10 000 µm). Six patients developed local recurrence (13 %; 95 % confidence interval [CI] 3.1 % - 22.4 %), and all were cured with organ-preserving intervention. After a median follow-up period of 71 months (range 27 - 116 months), one patient (2 %; 95 %CI 0 - 6.3 %) developed neck lymph node metastasis. A total of 14 patients (30 %) were followed for 5 years or more, and 5-year overall survival and disease-specific survival rates were 84.5 % (95 %CI 73 % - 96 %) and 100 %, respectively. CONCLUSIONS: Endoscopic resection has curative potential as a minimally invasive treatment option for SPSCC that invades the subepithelial layer.

Peritonitis related to percutaneous endoscopic gastrostomy using the direct method for cancer patients.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) using the direct method is generally indicated for cancer patients. However, there are little available data about peritonitis related to this method. The aim of this retrospective analysis was to assess peritonitis related to PEG using the direct method in patients with cancer. METHODS: We assessed the prevalence of peritonitis and the relationship between peritonitis and patients' backgrounds, as well as the clinical course after peritonitis. RESULTS: Between December 2008 and December 2011, peritonitis was found in 9 (2.1 %) of 421 patients. Of the 9 patients with peritonitis, 4 had received PEG prior to chemoradiotherapy. Emergency surgical drainage was required in 1 patient, and the remaining 8 recovered with conservative treatment. Peritonitis occurred within 8 days of PEG for 8 of the 9 patients and occurred within 2 days of suture removal for 4 of the 9 patients. CONCLUSION: Peritonitis related to PEG using the direct method was less frequent for cancer patients. Peritonitis tended to occur within a few days after removal of securing suture and in patients with palliative stage.

Usefulness of narrow-band imaging with dual-focus magnification for differential diagnosis of small colorectal polyps.

BACKGROUND: Many authors have already reported the usefulness of narrow-band imaging (NBI) for the differential diagnosis of non-neoplastic and neoplastic colorectal lesions. However, it is not clear whether magnification is required for differential diagnosis. The aim of this prospective study was to clarify the clinical usefulness of a newly developed NBI system with a dual focus function (dual-focus NBI) compared with conventional white-light imaging (WLI) and NBI without magnification for distinguishing between non-neoplastic and neoplastic lesions. PATIENTS AND METHODS: Thirty-seven consecutive patients who underwent screening colonoscopy with the novel system between July and December 2013 were analyzed. Patients with polyps >10 mm and those with polyps previously evaluated by histologic examination or colonoscopy were excluded. Lesions were diagnosed in real time with WLI, NBI without magnification, and dual-focus NBI, and then excised endoscopically. Each diagnosis was compared to that in the final histopathology reports. The primary endpoint was the diagnostic accuracy and the confidence level assigned to each modality by the endoscopists. The secondary endpoint was the differentiation ability according to the size of the lesion (≤5 and 6-10 mm). RESULTS: In all, 100 lesions including 76 adenomatous polyps and 24 hyperplastic polyps were analyzed in 37 patients. The overall diagnostic accuracy, sensitivity, and specificity for differentiating adenomatous from hyperplastic polyps were 87.0, 89.5, and 79.2 % for WLI, 93.0, 94.7, and 87.5 % for NBI without magnification, and 94.0, 96.1, and 87.5 % for dual-focus NBI, respectively. The level of confidence was significantly different between dual-focus NBI and WLI and NBI without magnification for diminutive (≤5 mm) lesions (p < 0.001 and p < 0.01). CONCLUSION: Dual-focus NBI is especially useful for differential diagnosis of diminutive colorectal lesions.