Depth of the cutting plane with underwater and conventional endoscopic mucosal resection: Post-hoc analysis of a randomized study.

BACKGROUND AND AIM: A multicenter randomized controlled trial reported a better R0 resection rate for intermediate-sized (10-20 mm) colorectal polyps with underwater endoscopic mucosal resection (UEMR) than conventional endoscopic mucosal resection (CEMR). To clarify whether UEMR removes enough submucosal tissue in the removal of unpredictable invasive cancers, we investigated the cutting plane depth with UEMR versus CEMR. METHODS: This was a post-hoc analysis of a randomized controlled trial in which 210 intermediate-sized colorectal polyps were removed in five Japanese hospitals. One pathologist and two gastroenterologists independently reviewed all resected specimens and measured the cutting plane depth. The cutting plane depth was evaluated as (i) maximum depth of submucosal layer and (ii) mean depth of submucosal layer, calculated using a virtual pathology system. RESULTS: We identified 168 appropriate specimens for the evaluation of the cutting plane depth, resected by UEMR (n = 88) and CEMR (n = 80). The median resection depth was not significantly different between UEMR and CEMR specimens, regardless of the measurement method ([i] 1317 vs 1290 µm, P = 0.52; [ii] 619 vs 545 µm, P = 0.32). All specimens in the UEMR and CEMR groups contained substantial submucosa and no muscularis propria. CONCLUSIONS: The cutting plane depth with UEMR was comparable with that with CEMR. UEMR can be a viable alternative method that adequately resects the submucosal layer for the histopathological assessment of unpredictable submucosal invasive cancers.

Prophylactic clipping not effective in preventing post-polypectomy bleeding for < 20-mm colon polyps: A multicenter, open-label, randomized controlled trial.

BACKGROUND AND AIM: Prophylactic clipping (PC) after polypectomy has the potential to prevent post-polypectomy bleeding (PPB). We aimed to evaluate the effectiveness of PC in preventing PPB for < 20-mm polyps. METHODS: This multicenter, open-label, randomized controlled trial conducted from December 2013 to June 2017 at 10 institutions randomly assigned 1080 patients with < 20-mm colon polyps to the non-PC and PC groups. Allocation factors were institution, antiplatelet drug use, and polyp number. The primary endpoint was differences in PPB rates between the groups. The severity of PPB and post-procedural abdominal symptoms were also investigated. These endpoints in intention-to-treat and per-protocol (PP) analyses were evaluated. RESULTS: We investigated 1039 patients with 2960 lesions. There was no significant difference between the groups in characteristics including age, sex, hypertension, diabetes, hyperlipidemia, antiplatelet drug use, and lesion characteristics such as type and size. Excluding the clip used in the non-PC group, intraoperative bleeding, and deviation of protocol, 903 patients were investigated in PP analysis. There was no significant difference in the PPB rate between the non-PC and PC groups (2.7% vs 2.3%, P = 0.6973 [intention-to-treat analysis]; 3.0 vs 2.4%, P = 0.7353 [PP analysis]). Severe PPB (≥ grade 3) was similar between the groups. Total procedure time was significantly shorter in the non-PC group than in the PC group (31 vs 36 min, P = 0.0002). Post-procedural abdominal fullness was less common in the non-PC group than in the PC group (20.8% vs 25.6%, P = 0.0833). CONCLUSION: Prophylactic clipping is not effective in preventing PBB for < 20-mm colon polyps (UMIN000012163).

Helicobacter pylori eradication prevents secondary gastric cancer in patients with mild-to-moderate atrophic gastritis.

BACKGROUND AND AIM: Whether Helicobacter pylori eradication prevents metachronous recurrence after endoscopic resection (ER) of early gastric cancer remains controversial. This multicenter retrospective study aimed to evaluate the long-term (> 5 years) effects of H. pylori eradication by stratifying patients' baseline degrees of atrophic gastritis. METHODS: A total of 483 H. pylori-positive patients who had undergone ER for early gastric cancer were divided into two groups-(i) those having undergone successful H. pylori eradication within 1 year after ER (eradicated group, n = 294) and (ii) those with failed or not attempted H. pylori eradication (non-eradicated group, n = 189). The cumulative incidences of metachronous gastric cancer between the two groups were compared for all patients, for patients with mild-to-moderate atrophic gastritis (n = 182), and for patients with severe atrophic gastritis (n = 301). RESULTS: During a median follow-up of 5.2 years (range 1.1-14.8), metachronous cancer developed in 52 (17.7%) patients in the eradicated group and in 35 (18.5%) patients in the non-eradicated group (P = 0.11, log-rank test). In patients with mild-to-moderate atrophic gastritis (111 and 71 in the eradicated and non-eradicated groups, respectively), the cumulative incidence of metachronous cancer was significantly lower in the eradicated group than that in the non-eradicated group (P = 0.03, log-rank test). However, no significant intergroup difference was observed in patients with severe atrophic gastritis (P = 0.69, log-rank test). CONCLUSIONS: Helicobacter pylori eradication had a preventive effect on the development of metachronous gastric cancer in patients with mild-to-moderate atrophic gastritis.

Comparison of Underwater vs Conventional Endoscopic Mucosal Resection of Intermediate-Size Colorectal Polyps.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) with submucosal injection is an established method for removing colorectal polyps, although the en bloc resection rate decreases when polyp size exceeds 10 mm. Piecemeal resection increases local recurrence. Underwater EMR (UEMR) is an effective technique for removal of sessile colorectal polyps and we investigated whether it is superior to conventional EMR (CEMR). METHODS: We conducted a multicenter randomized controlled trial at 5 institutions in Japan. Patients with endoscopically diagnosed, intermediate-size (10-20 mm) sessile colorectal lesions were randomly assigned to undergo UEMR or CEMR. Only the most proximal lesion was registered. The UEMR procedure included immersion of the entire lumen in water and snare resection of the lesion without submucosal injection of normal saline. We analyzed outcomes of 108 colorectal lesions in the UEMR group and 102 lesions in the CEMR group. R0 resection was defined as en bloc resection with a histologically confirmed negative resection margin. The primary endpoint was the difference in the R0 resection rates between groups. RESULTS: The proportions of R0 resections were 69% (95% confidence interval [CI] 59%-77%) in the UEMR group vs 50% (95% CI 40%-60%) in the CEMR group (P = .011). The proportions of en bloc resections were 89% (95% CI 81%-94%) in the UEMR group vs 75% (95% CI 65%-83%) in the CEMR group (P = .007). There was no significant difference in median procedure time (165 vs 175 seconds) or proportions of patients with adverse events (2.8% in the UEMR group vs 2.0% in the CEMR group). CONCLUSIONS: In a multicenter randomized controlled trial, we found that UEMR significantly increased the proportions of R0 resections for 10- to 20-mm sessile colorectal lesions without increasing adverse events or procedure time. Use of this procedure should be encouraged. Trials registry number: UMIN000018989.

Differentiation between duodenal neoplasms and non-neoplasms using magnifying narrow-band imaging - Do we still need biopsies for duodenal lesions?

OBJECTIVES: Endoscopic biopsies for nonampullary duodenal epithelial neoplasms (NADENs) can induce submucosal fibrosis, making endoscopic resection difficult. However, no biopsy-free method exists to distinguish between NADENs and non-neoplasms. We developed a diagnostic algorithm for duodenal neoplasms based on magnifying endoscopy findings and evaluated the model's diagnostic ability. METHODS: Magnified endoscopic images and duodenal lesion histology were collected consecutively between January 2015 and April 2016. Diagnosticians classified the surface patterns as pit, groove or absent. In cases of nonvisible surface patterns, the vascular pattern was evaluated to determine regularity or irregularity. The correlation between our algorithm (pit-type or absent with irregular vascular pattern) and the lesion histology were evaluated. Four evaluators, who were blinded to the histology, also classified the endoscopic findings and evaluated the diagnostic performance and interobserver agreement. RESULTS: Endoscopic images of 114 lesions were evaluated (70 NADENs and 44 non-neoplasms, 31 in the superior and 83 in the descending and horizontal duodenum). Of the NADEN surface patterns, 88% (62/70) were pit-type, while 79% (35/44) of the non-neoplasm surface patterns were groove-type. Our diagnostic algorithm for differentiating NADENs from non-neoplasms was high (sensitivity 96%, specificity 95%) in the descending and horizontal duodenum. The evaluators' diagnostic performances were also high, and interobserver agreement for the algorithm was good between each diagnostician and evaluator (κ = 0.60-0.76). CONCLUSION: Diagnostic performance of our algorithm sufficiently enabled eliminating endoscopic biopsies for diagnosing the descending and horizontal duodenum.

[A case of idiopathic thrombocytopenic purpura development after total colectomy for ulcerative colitis].

Ulcerative colitis (UC) is known to be associated with extraintestinal manifestations. However, idiopathic thrombocytopenic purpura (ITP) has rarely been reported as one of the extraintestinal manifestations in UC. In most cases, ITP develops as an extraintestinal manifestation during the treatment for UC. After treatment with medications or colectomy, there is often a remission of UC and ITP. However, we experienced a case of ITP development after total colectomy for UC. An 83-year-old man was diagnosed as having UC and started treatment with medications. After 3 years, total colectomy and ileostomy were performed to prevent UC remission. Subsequently, no further treatment was provided. Two years later, he presented to the hematology department in our hospital with the chief complaint of thrombocytopenia and was diagnosed as having ITP. ITP was treated with steroids, and his platelet count increased to within the normal range. Immunological abnormalities may be involved in the development of extraintestinal manifestation, including UC-associated ITP. In previous reports, ITP was cured by colectomy for UC. In contrast, peripheral arthritis is a common extraintestinal manifestation of UC, and it is known that 75% of these patients develop or continue to experience such symptoms after colectomy. Some extraintestinal manifestations may equally persist after colectomy. However, the underlying mechanisms are poorly understood. Ileitis and small intestinal and duodenal inflammation are all known bowel complications associated with colectomy, and some immunological mechanisms have been suggested to be involved. Therefore, careful monitoring in these patients is necessary to detect any possibility of developing extraintestinal manifestations after colectomy. Further studies to examine the mechanisms underlying the immunological abnormality between UC and extraintestinal manifestations such as ITP are needed.

Favorable outcome with direct-acting antiviral treatment in hepatitis C patients coinfected with HIV.

AIM: To investigate the efficacy and safety of all-oral direct-acting antiviral treatments in patients coinfected with hepatitis C virus (HCV) and HIV. METHODS: In all, 35 patients with HCV/HIV coinfection (22 patients with HCV genotype 1 infection, 6 with genotype 2, and 7 with genotype 3) were treated with sofosbuvir and ledipasvir (for genotype 1 patients) or sofosbuvir and ribavirin (for genotypes 2 and 3). Sustained virological response (SVR) at 24 weeks after end of treatment and adverse events were assessed. RESULTS: The overall SVR rate was 91.4% (32/35). One patient with genotype 1 infection discontinued treatment on day 2 due to severe headache, which subsided after the cessation of medication; all other patients completed their treatment without severe adverse events. Two patients who had a relapse of HCV were infected with a genotype 3 strain. We observed hyperbilirubinemia in a patient with genotype 3, who was under antiretroviral therapy including atazanavir. He completed the treatment and achieved SVR. CONCLUSION: Direct-acting antiviral treatment for patients coinfected with HCV/HIV is as effective as in patients infected only with HCV. It was generally well tolerated, except in one patient who discontinued the treatment due to severe headache.

[A case of refractory pouchitis following surgery for ulcerative colitis successfully treated with adalimumab].

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as the operation of choice for refractory ulcerative colitis (UC), UC with dysplasia or cancer, or familial adenomatous polyposis. Pouchitis is the most frequent complication after IPAA for UC. Although the pathogenesis of pouchitis remains unclear, current evidence suggests that dysbiosis and mucosal immune response are important mechanisms. Antibiotics are the first-line treatment for the condition, but some patients develop chronic refractory pouchitis. Such cases can be treated with regimens such as longer courses of antibiotic combinations, mesalazine, corticosteroids, probiotics, or biologics. But if pouch inflammation is not ameliorated, a permanent ileostomy may be required. A 40-year-old man had undergone IPAA for UC and was diagnosed with pouchitis according to the Pouchitis Disease Activity Index. Antibiotics, mesalazine, and corticosteroids were given, but the inflammation was difficult to control. He developed chronic refractory pouchitis associated with perianal abscesses and anal fistulae. Following a seton procedure for fistulae, adalimumab (ADA) was administered. After 42 weeks, the ulcers in the pouch became scarred, and the anal fistulae were closed endoscopically. After remission was induced, it has been maintained. ADA is a fully human anti-tumor necrosis factor-α (TNF-α) monoclonal antibody that has been successfully used to treat refractory Crohn disease of the ileoanal pouch. Although some studies report that infliximab, a chimeric anti-TNF-α monoclonal antibody, is efficacious in patients with refractory pouchitis, clinical evidence for the use of ADA is limited. This case illustrates achievement of induction and maintenance of remission of refractory pouchitis with ADA. It is possible that patients with this condition can avoid a permanent ileostomy with anti-TNF-α therapy. In the near future, further study of long-term clinical outcomes of anti-TNF-α therapy is expected.

Erratum: Dive to the Underwater World: A Water Immersion Technique for Endoscopic Submucosal Dissection of Gastric Neoplasms.

This corrects the article DOI: 10.1038/ajg.2016.595.

Endoscopic Balloon Dilation Followed By Intralesional Steroid Injection for Anastomotic Strictures After Esophagectomy: A Randomized Controlled Trial.

OBJECTIVE: Endoscopic balloon dilation (EBD) is a standard treatment for anastomotic strictures after esophagectomy, and requires multiple dilations. We conducted a randomized controlled trial to assess the efficacy of adding a steroid injection to EBD to reduce restricture. METHODS: Patients were randomized to receive EBD combined with either triamcinolone or placebo injection. The primary endpoint was the number of dilations required to resolve the stricture. The secondary endpoints were restricture-free survival and adverse events. Patients with a dysphagia symptom score of ≥2 after esophagectomy with an endoscopy-confirmed anastomotic stricture were included. A total of 50 mg of triamcinolone acetonide (50 mg/5 mL) or an identical volume of normal saline solution as a placebo was injected per site using a 25-gauge needle immediately after EBD. Both the patient and treating physician were blinded to the treatment given. RESULTS: During the 4-year study period, 65 patients were randomized to either the steroid group (n = 33) or placebo group (n = 32). The median number of EBDs required to resolve strictures was 2.0 (interquartile range, 1.0-2.5) in the steroid group and 4.0 (interquartile range, 2.0-6.8) in the placebo group (p < 0.001). After 6 months of follow-up, 39% of patients who had received steroid injections remained recurrence free compared with 16% of those who had received saline injections (p = 0.002). No adverse events occurred during follow-up. CONCLUSIONS: Steroid injection shows promising results for the prevention of stricture recurrence in patients who underwent EBD for anastomotic strictures.

Underwater endoscopic mucosal resection for superficial nonampullary duodenal adenomas.

BACKGROUND AND STUDY AIM: Underwater endoscopic mucosal resection (UEMR) was recently developed in a Western country. A prospective cohort study to investigate the effectiveness of UEMR was conducted in patients with small superficial nonampullary duodenal adenomas. PATIENTS AND METHODS: Patients with duodenal adenomas ≤ 20 mm were enrolled. After the duodenal lumen had been filled with physiological saline, UEMR was performed without submucosal injection. Endoclip closure was attempted for all mucosal defects after UEMR. Follow-up endoscopy with biopsy was performed 3 months later. The primary end point was the complete resection rate, defined as neither endoscopic nor histological residue of adenoma at the follow-up endoscopy. RESULTS: 30 patients with 31 lesions were enrolled. The mean (SD) tumor size was 12.0 mm (7.3). The complete resection rate was 97 % (90 % confidence interval, 87 % - 99 %). The en bloc resection rate was 87 %. All mucosal defects were successfully closed by endoclips. No adverse events occurred except for one case of mild aspiration pneumonia. CONCLUSIONS: UEMR is efficacious for the treatment of small duodenal adenomas, but further large-scale trials are warranted to confirm these results.

Safety of cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective exploratory study.

BACKGROUND: Cold snare polypectomy (CSP) to remove multiple duodenal adenomas (MDAs) in patients with familial adenomatous polyposis (FAP) could be an effective and less invasive method than more extensive surgery. The aim of the present study was to determine the safety of this procedure. METHODS: This prospective exploratory study included 10 consecutive patients with FAP and MDAs who underwent CSP for as many as 50 duodenal adenomas. The primary outcome was the incidence of severe adverse events. RESULTS: 10 patients were enrolled and underwent 332 CSPs from June 2016 to January 2017. The median procedure time was 33 minutes (range 25 - 53), and the median number of polyps removed during a single session was 35 (range 10 - 50). Most of the removed polyps were ≤ 10 mm. None of the 10 patients experienced a severe adverse event. One patient developed arterial bleeding during the procedure, but it was easily managed using hemoclips. CONCLUSIONS: CSP for MDAs in patients with FAP was safe. The long-term efficacy of this procedure should be investigated.

"Underwater" endoscopic submucosal dissection: a novel method for resection in saline with a bipolar needle knife for colorectal epithelial neoplasia.

BACKGROUND: Despite improvements in therapeutic strategy and instrumentation in colorectal endoscopic submucosal dissection (ESD), adverse events sometimes occur. Further advancements in available techniques are required to improve procedural success rates and safety. We developed a novel method for ESD in saline, referred to as "underwater" ESD (UESD). UESD involves using a bipolar needle knife and aims to enable complete resection while minimizing thermal damage to the muscle layer. In this study, we evaluated the safety and efficacy of this new technique. METHODS: This was a retrospective study using data from two referral centers and included 40 lesions diagnosed as colorectal epithelial neoplasia (> 20 mm in diameter or with severe fibrosis) and treated with UESD between December 2015 and March 2017. The main outcome measures were technical success rate, incidence of adverse events, and feasibility of histologic evaluation of the resected specimens. RESULTS: All 40 lesions, including those with submucosal fibrosis, underwent successful en bloc resection using the UESD technique. No procedural adverse events including perforation, delayed bleeding, and electrocoagulation syndrome were observed, and all patients had an uneventful clinical course associated with UESD. In all cases, UESD provided a resected specimen adequate for histological evaluation, without unwarranted burn effect to the tissues. CONCLUSIONS: Our UESD technique was safe and effective for complete resection of colorectal epithelial neoplasia.

Efficacy of traction-assisted colorectal endoscopic submucosal dissection using a clip-and-thread technique: A prospective randomized study.

BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) remains challenging because of technical difficulties, long procedure time, and high risk of adverse events. To facilitate colorectal ESD, we developed traction-assisted colorectal ESD using a clip and thread (TAC-ESD) and conducted a randomized controlled trial to evaluate its efficacy. METHODS: Patients with superficial colorectal neoplasms (SCN) ≥20 mm were enrolled and randomly assigned to the conventional-ESD group or to the TAC-ESD group. SCN ≤50 mm were treated by two intermediates, and SCN >50 mm were treated by two experts. Primary endpoint was procedure time. Secondary endpoints were TAC-ESD success rate (sustained application of the clip and thread until the end of the procedure), self-completion rate by the intermediates, and adverse events. RESULTS: Altogether, 42 SCN were analyzed in each ESD group (conventional and TAC). Procedure time (median [range]) for the TAC-ESD group was significantly shorter than that for the conventional-ESD group (40 [11-86] min vs 70 [30-180] min, respectively; P < 0.0001). Success rate of TAC-ESD was 95% (40/42). The intermediates' self-completion rate was significantly higher for the TAC-ESD group than for the conventional-ESD group (100% [39/39] vs 90% [36/40], respectively; P = 0.04). Adverse events included one intraoperative perforation in the conventional-ESD group and one delayed perforation in the TAC-ESD group. CONCLUSION: Traction-assisted colorectal endoscopic submucosal dissection reduced the procedure time and increased the self-completion rate by the intermediates (UMIN000018612).

Transoral endoscopic examination of head and neck region.

Transoral endoscopy with narrow band imaging (NBI) is useful for early detection of head and neck (HN) cancer. However, the lateral and anterior walls of the oropharynx, postcricoid area, and posterior wall of the hypopharynx are difficult to observe using transoral endoscopy. Advanced cancers in these regions may be missed even when NBI is used. This report highlights a method of transoral endoscopic examination of the HN region. For observation of the oral cavity and oropharynx, it is important to observe these regions without using a mouthpiece. Wide opening of the mouth facilitates observation of the oral cavity and oropharynx. Moreover, visibility of the oropharynx, including the anterior wall, is dramatically improved, when the patient positions the tongue forward and says 'aaah.' This technique also facilitates observation of the dorsum of the tongue, which is difficult to observe from a tangential view when using a mouthpiece. To observe the hypopharynx, the Valsalva maneuver is very useful. Patient cooperation is important when observing the HN region thoroughly to gain clear endoscopic views. Narcotic drugs, such as pethidine hydrochloride, are ideal for conscious sedation and reduce the gag reflex while still allowing patient cooperation. From the oral cavity to the hypopharynx, including the lateral and anterior walls of the oropharynx, postcricoid area, and posterior wall of the hypopharynx, most of the HN region can be observed during routine examination using transoral endoscopy without any special devices.

Line-assisted complete closure for a large mucosal defect after colorectal endoscopic submucosal dissection decreased post-electrocoagulation syndrome.

BACKGROUND AND AIM: The incidence of post-endoscopic submucosal dissection (ESD) coagulation syndrome (PECS) can be decreased by closing mucosal defects. However, large mucosal defects after colorectal ESD cannot be closed endoscopically. We established line-assisted complete clip closure (LACC), a novel technique for large mucosal defects after colorectal ESD. We evaluated the prophylactic efficacy of LACC for preventing PECS. METHODS: Sixty-one consecutive patients on whom LACC after colorectal ESD was attempted from January 2016 to August 2016 were analyzed. After exclusion of patients with incomplete LACC and adverse events during ESD, 57 patients comprised the LACC group. In contrast, 495 patients who did not undergo closure of a mucosal defect comprised the control group. Propensity score matching was used to adjust for patients' backgrounds. Treatment outcomes were evaluated between the groups. RESULTS: Median resected specimen size in the LACC-attempted group was 35 mm (range, 20-72 mm), and LACC success rate was 95% (58/61). Median procedure time of LACC was 14 min. In the LACC group, incidence of PECS was only 2%, and no delayed bleeding or perforation occurred. Propensity score matching created 51 matched pairs. Adjusted comparisons between the LACC and control groups showed a lower incidence of PECS (0% vs 12%, respectively; P = 0.03) and shorter hospitalization (5 vs 6 days, respectively; P < 0.001) in the LACC group. CONCLUSION: This study suggests that LACC can effectively reduce the incidence of PECS, although further large-scale studies are warranted.

Incomplete resection rate of cold snare polypectomy: a prospective single-arm observational study.

Background and study aims Cold snare polypectomy (CSP) is considered to be safe for the removal of subcentimeter colorectal polyps. This study aimed to determine the rate of incomplete CSP resection for subcentimeter neoplastic polyps at our center. Patients and methods Patients with small or diminutive adenomas (diameter 1 - 9 mm) were recruited to undergo CSP until no polyp was visible. After CSP, a 1 - 3 mm margin around the resection site was removed using endoscopic mucosal resection. The polyps and resection site marginal specimens were microscopically evaluated. Incomplete resection was defined as the presence of neoplastic tissue in the marginal specimen. We also calculated the frequency at which the polyp lateral margins could be assessed for completeness of resection. Results A total of 307 subcentimeter neoplastic polyps were removed from 120 patients. The incomplete resection rate was 3.9 % (95 % confidence interval [CI] 1.7 % - 6.1 %); incomplete resection was not associated with polyp size, location, morphology, or operator experience. The polyp lateral margins could not be assessed adequately for 206 polyps (67.1 %). Interobserver agreement between incomplete resection and lateral polyp margins that were inadequate for assessment was poor (κ = 0.029, 95 %CI 0 - 0.04). Female sex was an independent risk factor for incomplete resection (odds ratio 4.41, 95 %CI 1.26 - 15.48; P  = 0.02). Conclusions At our center, CSP resection was associated with a moderate rate of incomplete resection, which was not associated with polyp characteristics. However, adequate evaluation of resection may not be routinely possible using the lateral margin from subcentimeter polyps that were removed using CSP.Trial registered at University Hospital Medical Information Network (UMIN 000010879).

Endoscopic imaging modalities for diagnosing invasion depth of superficial esophageal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Diagnosis of cancer invasion depth is crucial for selecting the optimal treatment strategy in patients with gastrointestinal cancers. We conducted a meta-analysis to determine the utilities of different endoscopic modalities for diagnosing invasion depth of esophageal squamous cell carcinoma (SCC). METHODS: We conducted a comprehensive search of MEDLINE, Cochrane Central, and Ichushi databases to identify studies evaluating the use of endoscopic modalities for diagnosing invasion depth of superficial esophageal SCC. We excluded case reports, review articles, and studies in which the total number of patients or lesions was <10. RESULTS: Fourteen studies fulfilled our criteria. Summary receiver operating characteristic curves showed that magnified endoscopy (ME) and endoscopic ultrasonography (EUS) performed better than non-ME. ME was associated with high sensitivity and a very low (0.08) negative likelihood ratio (NLR), while EUS had high specificity and a very high (17.6) positive likelihood ratio (PLR) for the diagnosis of epithelial or lamina propria cancers. NLR <0.1 provided strong evidence to rule out disease, and PLR >10 provided strong evidence of a positive diagnosis. CONCLUSIONS: EUS and ME perform better than non-ME for diagnosing invasion depth in SCC. ME has a low NLR and is a reliable modality for confirming deep invasion of cancer, while EUS has a high PLR and can reliably confirm that the cancer is limited to the surface. Effective use of these two modalities should be considered in patients with SCC. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews); number 42015024462 .

Pethidine hydrochloride is a better sedation method for pharyngeal observation by transoral endoscopy compared with no sedation and midazolam.

BACKGROUND AND AIM: Standard surveillance methods for pharyngeal cancer have not been established. We conducted a randomized controlled trial to investigate the best sedation method for pharyngeal observation using transoral endoscopy. METHODS: In total, 120 patients who underwent surveillance or diagnostic examinations for esophageal cancer were enrolled and divided equally into three groups (no sedation, midazolam, or pethidine hydrochloride). In the midazolam group, midazolam was given i.v. maintaining a Ramsay score of 3. In the pethidine group, pethidine hydrochloride (35 mg) given i.v. Seven sites in five pharyngeal regions were observed on insertion of the endoscope, and graded (0 = poor, 1 = good). After examination, the five pharyngeal regions were scored using a seven-point scale. Primary endpoint was the total score from the five pharyngeal regions. Secondary endpoints were the proportion of the perfect score using the seven-point scale, discomfort score, and adverse events. RESULTS: Mean total scores for the no sedation group, the midazolam group and the pethidine group were 5.7, 5.5, and 6.8, respectively (P < 0.0001). Proportion of patients with a perfect score for the no sedation group, the midazolam group and the pethidine group were 53%, 35%, and 89%, respectively (P < 0.0001). The pethidine group had better results than the other two groups. Discomfort score and adverse events were low in the pethidine group. CONCLUSION: Pethidine hydrochloride is a feasible and safe sedation method, and was superior to no sedation and midazolam regarding pharyngeal observation of esophageal cancer patients.

p53 functional deficiency in human colon cancer cells promotes fibroblast-mediated angiogenesis and tumor growth.

Cancer-associated fibroblasts (CAFs) create a microenvironment that contributes to tumor growth; however, the mechanism by which fibroblasts are phenotypically altered to CAFs remains unclear. Loss or mutation of the tumor suppressor p53 plays a crucial role in cancer progression. Herein, we analyzed how the p53 status of cancer cells affects fibroblasts by investigating the in vivo and in vitro effects of loss of p53 function in cancer cells on phenotypic changes in fibroblasts and subsequent tumor progression in human colon cancer cell lines containing wild-type p53 and in cells with a p53 functional deficiency. The growth of p53-deficient tumors was significantly enhanced in the presence of fibroblasts compared with that of p53-wild-type tumors or p53-deficient tumors without fibroblasts. p53-deficient cancer cells produced reactive oxygen species, which activated fibroblasts to mediate angiogenesis by secreting vascular endothelial growth factor (VEGF) both in vivo and in vitro Activated fibroblasts significantly contributed to tumor progression. Deletion of fibroblast-derived VEGF or treatment with N-acetylcysteine suppressed the growth of p53-deficient xenograft tumors. The growth effect of blocking VEGF secreted from cancer cells was equivalent regardless of p53 functional status. Human colon cancer tissues also showed a significant positive correlation between p53 cancer cell staining activated fibroblasts and microvessel density. These results reveal that fibroblasts were altered by exposure to p53-deficient epithelial cancer cells and contributed to tumor progression by promoting neovascularization. Thus, p53 acts as a modulator of the tumor microenvironment.