Zhong Ren

Peroral Endoscopic Myotomy for the Treatment of Achalasia: A Clinical Comparative Study of Endoscopic Full-Thickness and Circular Muscle Myotomy

BACKGROUND A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. STUDY DESIGN According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. RESULTS The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). CONCLUSIONS Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.

Complete closure of large gastric defects after endoscopic full-thickness resection, using endoloop and metallic clip interrupted suture

BACKGROUND AND STUDY AIM Successful closure of wall defects is the key procedure following endoscopic full-thickness resection (EFTR). In this report we describe a new method similar to interrupted suture to repair gastric defects by means of endoloops and metallic clips. PATIENTS AND METHODS We retrospectively analyzed 20 patients who presented at our institute between March 2011 and February 2012 with gastric submucosal tumors and who consequently underwent EFTR, with the resulting large gastric defects being closed using endoloops and metallic clips. Tumor characteristics, en bloc resection rates, and postoperative complications were evaluated in all the patients. RESULTS The median age of the 20 patients was 47 years. The mean maximum size of lesions was 1.47 ± 0.72 cm (range 0.4 - 3 cm). All lesions were diagnosed by endoscopic ultrasound as tumors in the muscularis propria layer. The en bloc resection rate was 100 %. Five patients developed fever and complained of slight abdominal pain in the first day after treatment. No patient had severe complications such as peritonitis or abdominal abscess. In all cases, wounds healed after 1 month. We observed the persistence of the clips for over 3 months in 6 out of 19 cases without any clinical manifestations or large injury to the intestine. CONCLUSIONS Our study provides evidence that the use of metallic clips and endoloops is a relatively safe, easy, and feasible method for repairing gastric defects resulting from EFTR.

MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1α (FIH-1)

The molecular mechanisms underlying colorectal cancer (CRC) tumorigenesis remain incompletely understood, partially contributing to the mortality of CRC. Advances in identification of novel mechanisms are therefore in an urgent need to fill the gap of our knowledge in CRC development. Here, we performed both in vitro and in vivo experiments along with in silico analysis to identify a new regulatory circuit that stimulated CRC tumorigenesis. In this report, we, for the first time, analyzed the correlation of FIH-1 level with clinicopathological features of CRC. The finding that FIH-1 was not only significantly decreased in tumor tissue as compared with the adjacent normal tissue but also was significantly correlated with tumor T stage status, indicated the role of FIH-1 as a tumor suppressor in CRC development. Moreover, we found the expression of miR-31, a short non-coding RNA which played a critical role in CRC development, was negatively correlated with FIH-1 expression in CRC samples and cell lines. Together with the result from luciferase report assay, it was demonstrated that miR-31 could directly regulate FIH-1 expression in CRC. This miR-31/FIH-1 nexus was further shown to control cell proliferation, migration and invasion in vitro and to control tumor growth in vivo. Additionally, correlation of the miR-31 expression with clinicopathologic features in CRC samples was examined in support of the driving role of newly identified miR-31/FIH-1 nexus in CRC tumorigenesis. These findings highlight the critical role of miR-31/FIH-1 nexus in CRC and reveal the contribution of miR-31 to CRC development by targeting FIH-1.

Factor inhibiting HIF1α (FIH-1) functions as a tumor suppressor in human colorectal cancer by repressing HIF1α pathway.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The molecular mechanisms underlying CRC development involve a multistep process with the accumulation of both genetic and epigenetic changes. To deeply understand CRC tumorigenesis and progression, advances in identification of novel mechanisms and key factors are therefore in an urgent need. Here, we examined the correlation of factor inhibiting HIF-1α (FIH-1) expression with clinicopathological features of CRC. The finding that FIH-1 was not only significantly decreased in tumor tissue but also was significantly correlated with tumor invading depth, lymph node involvement, and metastasis suggested the role of FIH-1 as a tumor suppressor in CRC development. To further support the above hypothesis, we performed both in vitro and in vivo experiments to identify the role of FIH-1 in CRC development. FIH-1 was found to inhibit CRC cell proliferation, migration, invasion, and colony formation in vitro. FIH-1 was also shown to repress LOVO xenograft tumor growth in vivo. To decipher the mechanism, we examined the expression level of HIF-1α and its target genes. We found that FIH-1 was able to inhibit HIF1α mediated transcription of GLUT1 and VEGF in CRC cells. The above observation points to the possibility that loss or decreased expression of FIH-1 gene may lead to a constitutive activation of HIF1α and an alteration of HIF-1 targets such as GLUT-1 and VEGF. These findings highlight the critical role of FIH-1 in CRC and indicate FIH-1 functions as a tumor suppressor in human CRC by repressing HIF1α pathway.

Peroral Endoscopic Myotomy for Esophageal Achalasia by HybridKnife: A Case Report.

This paper presented a case of esophageal achalasia treated by peroral endoscopic myotomy with HybridKnife and discuss the feasibility and the possible advantages of using it.

Self-expandable metallic stent placement plus laparoscopy for acute malignant colorectal obstruction.

AIM To investigate the clinical advantages of the stent-laparoscopy approach to treat colorectal cancer (CRC) patients with acute colorectal obstruction (ACO). METHODS From April 2008 to April 2012, surgery-related parameters, complications, overall survival (OS), and disease-free survival (DFS) of 74 consecutive patients with left-sided CRC presented with ACO who underwent self-expandable metallic stent (SEMS) placement followed by one-stage open (n = 58) or laparoscopic resection (n = 16) were evaluated retrospectively. The stent-laparoscopy group was also compared with a control group of 96 CRC patients who underwent regular laparoscopy without ACO between January 2010 and December 2011 to explore whether SEMS placement influenced the laparoscopic procedure or reduced long-term survival by influencing CRC oncological characteristics. RESULTS The characteristics of patients among these groups were comparable. The rate of conversion to open surgery was 12.5% in the stent-laparoscopy group. Bowel function recovery and postoperative hospital stay were significantly shorter (3.3 ± 0.9 d vs 4.2 ± 1.5 d and 6.7 ± 1.1 d vs 9.5 ± 6.7 d, P = 0.016 and P = 0.005), and surgical time was significantly longer (152.1 ± 44.4 min vs 127.4 ± 38.4 min, P = 0.045) in the stent-laparoscopy group than in the stent-open group. Surgery-related complications and the rate of admission to the intensive care unit were lower in the stent-laparoscopy group. There were no significant differences in the interval between stenting and surgery, intraoperative blood loss, OS, and DFS between the two stent groups. Compared with those in the stent-laparoscopy group, all surgery-related parameters, complications, OS, and DFS in the control group were comparable. CONCLUSION The stent-laparoscopy approach is a feasible, rapid, and minimally invasive option for patients with ACO caused by left-sided CRC and can achieve a favorable long-term prognosis.

Down-regulation of Smad4 enhances proliferation and invasion of colorectal carcinoma HCT116 cells and up-regulates Id2.

The aim of this study was to determine whether the suppression of Smad4 by short hairpin RNA (shRNA) regulates the proliferation and invasion of colorectal carcinoma HCT116 cells and Id2 expression. The Smad4‑shRNA expression vectors were constructed and stably transfected to HCT116 cells. The expression of mRNA and protein of Smad4 and Id2 was detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Cellular proliferation inhibitory activity was determined by methyl thiazolyl tetrazolium (MTT) assay. Transwell assay was used to detect the effect of the inhibition of Smad4-shRNA on migration and invasion. The Smad4-shRNA vector, which inhibited Smad4 expression, was constructed and successfully transfected to HCT116 cells. The levels of mRNA and protein expression of Smad4 were markedly decreased following transfection of shRNA compared with the control groups (P<0.05). The abilities of proliferation, migration and invasion were increased following transfection of shRNA (P<0.05). The expression of Id2 was increased following transfection of shRNA (P<0.05). For the Smad4-down-regulated HCT116 cells, treated with or without BMP7 (25 ng/ml), no difference was found. shRNA-mediated silencing of Smad4 was able to enhance the abilities of proliferation, migration and invasion in the HCT116 cell line. Therefore, Smad4 may act as a tumor-suppressor gene in colorectal carcinoma.

Endoscopic submucosal dissection for early esophageal cancer in elderly patients with relative indications for endoscopic treatment

BACKGROUND According to the Japanese Esophageal Society (JES) guidelines, early esophageal squamous cell carcinoma (SCC) involving the muscularis mucosae (M3) or upper submucosal (SM1) layers are relative indications for endoscopic submucosal dissection (ESD). Additional esophagectomy or chemoradiotherapy is recommended for patients with relative indications after evaluation. However, elderly patients (≥ 60 years) with relative indications in China often refuse additional treatment because of the debilitating side effects. The aim of this study was to evaluate the long-term outcomes of elderly patients with relative indications who did not undergo additional treatment after ESD. METHODS Data from elderly patients with relative indications who underwent ESD for early esophageal SCC between January 2008 and December 2013 were reviewed retrospectively. Stricture and recurrence, and 5-year progression-free survival (PFS) and overall survival rates were compared with patients with absolute indications for ESD. RESULTS 158 elderly patients were included and analyzed (89 in the absolute indications group and 69 in the relative indications group). The baseline characteristics were balanced between the two groups. During 56 months (range 1 - 108) of follow-up, the postoperative stricture rates were similar in the absolute and relative indications groups (21.3 % vs. 31.9 %; P  = 0.13). The hazard ratio (HR) for PFS in the absolute vs. the relative indications groups was 1.025 (95 % confidence interval [CI] 0.36 - 2.95; P = 0.96). The 5-year PFS rates were 90.5 % (95 %CI 83.44 - 97.56) and 90.8 % (95 %CI 83.74 - 97.86) for the absolute and relative indications groups, respectively. The HR for overall survival in the absolute vs. the relative indications groups was 0.564 (95 %CI 0.13 - 2.52; P = 0.45). The 5-year overall survival rates were 96.6 % (95 %CI 92.88 - 100) and 95.6 % (95 %CI 90.70 - 100) for the absolute and relative indications groups, respectively. CONCLUSIONS Based on this study, regular follow-up without additional treatment may be considered as another choice for elderly patients with early esophageal SCC and relative indications after ESD.