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Cisplatin is one of the most predominant drugs for the chemotherapy of esophageal squamous cell carcinoma (ESCC); however, the underlying resistance mechanisms are still almost unknown. The present study performed RNA sequencing of human circular RNA (circRNA) in TE11 cells and cisplatin-resistant TE11 cells (TE11R). The expression profiles determined using CIRCexplorer2 revealed that the expression of circ_0004365, mapped on the Semaphorin 3C gene, was significantly greater in TE11R compared with in TE11. In reverse transcription-quantitative PCR, circ_0004365 expression was observed in human ESCC and non-tumor tissues and was significantly upregulated in ESCC tumor tissues after chemotherapy. Circ_0004365 expression was significantly upregulated in patients with poor pathological response (P=0.02). Furthermore, patients with advanced pT stage showed an upregulation in circ_0004365 expression after chemotherapy (P=0.02). The MTT assay revealed that knockdown of circ_0003465 in TE11 significantly decreased resistance to cisplatin. In conclusion, the present study suggested that circ_0004365 was associated with cisplatin resistance in ESCC and can be used as both a novel biomarker and a therapeutic target. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29-4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target. [ABSTRACT FROM AUTHOR]

Programmed death‑ligand 1 (PD‑1/PD‑L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD‑L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair‑deficient tumors are associated with improved survival, although they are not sensitive to 5‑fluorouracil‑based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD‑L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD‑L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD‑L1 expression. The 5‑year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (P<0.0001). The frequency of high PD‑L1 expression was 11.4% in the high MLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD‑L1 expression. [ABSTRACT FROM AUTHOR]

Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses. HSF1 protein and mRNA expression were assessed in resected specimens from 270 patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression were also assessed in 55/270 patients. Patients with high HSF1 expression had a significantly worse OS than those with low HSF1 expression in both cohorts. In multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73; 95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64; P=0.0002) were statistically significant independent prognostic factors. Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1 expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27 and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC. [ABSTRACT FROM AUTHOR]

Esophageal cancers frequently metastasize to recurrent laryngeal nerve lymph nodes (RLNNs). Knowledge of anatomic metastatic RLNN (mRLNN) distributions is needed for lymph node dissection during esophageal cancer surgery. Among 189 patients with esophageal cancer who underwent esophagectomy between 2008 and 2010, 51 (27.0%) had mRLNN. Sixty-four mRLNNs (right, 31; left, 33) were identified via preoperative computed tomography (CT); more than 2 unilateral metastases and/or nodes with unclear boundaries were excluded. Anatomical characteristics, including vertical distance from the sternal notch level, circumferential angle to the mid-sagittal tracheal plane, and short and long axes, were measured via CT. Respective mean right and left vertical distances from the sternal notch were +2.0±13.1 mm and -14.5±23.8 mm (p=0.0006). Left mRLNNs existed in vertically wider and inferior areas along recurrent laryngeal nerve, compared to right mRLNNs. The respectivemean right and left circumferential angles around the trachea (from the anterior mid-sagittal plane) were 137.2±11.2 and 94.3±31.6 (p<0.0001). LeftmRLNNs were distributed more widely around the trachea, especially anteriorly. The short axes were larger for right mRLNNs than for left mRLNNs (8.6 mm vs. 6.8 mm, p=0.026). Compared with the right side, left mRLNNs were smaller and had a vertically longer and circumferentially wider distribution. Careful attention should be given to the left side during curative RLNN dissection. [ABSTRACT FROM AUTHOR]

Background and study aims: Gastric reflux into the remnant esophagus after subtotal or partial esophagectomy is associated with impairment in patient quality of life.We evaluated the feasibility, safety, and potential effectiveness of a novel procedure using a new endoscopic suturing device to create an anti-reflux valve (funnel) in pigs after esophagectomy with gastric tube reconstruction. Methods: The endoscopic procedure was performed in four pigs using a semi-full-thickness endoscopic suturing system (OverStitch; Apollo Endosurgery, Austin, Texas, USA). The operating time, funnel height, ratio of the height of the funnel to the diameter of the gastric tube, and adverse events associated with the procedure were evaluated. The "reflux angle" was measured morphologically and functionally during a reflux induction test, using contrast medium or artificial gastric fluid, by tilting the operating table gradually from a head up to a head down position. Reflux angles before and after funnel creation were compared. Results: The procedure was successful in all four animals. The median operating time was 43 minutes, and the median funnel height was 17mm (56.7% of gastric tube diameter). There were no adverse events associated with the procedure. The reflux angle was lower after the procedure compared with before in both morphological and functional assessments in all four cases. Conclusions: Endoscopic anti-reflux funnel creation using OverStitch was feasible, safe, and potentially effective. [ABSTRACT FROM AUTHOR]

Background and Aims: Automatic smoke evacuation has not been feasible inside the gastrointestinal tract as evacuation collapses pneumoviscera. As previously reported, steady pressure automatically controlled endoscopy (SPACE) may resolve this problem. The aims of this study were to clarify the potential dangers of surgical smoke, and to evaluate the feasibility and potential usefulness of automatic smoke evacuation in flexible gastrointestinal endoscopy. Methods: Seven pigs were enrolled. SPACE was established by using a flexible endoscope, an overtube, and a surgical CO2 insufflator. Smoke was generated by gastric mucosal ablation for component analysis and was evacuated by a commercially available surgical-use smoke evacuator connected to an additional line attached to the endoscope. Endoscopic images with evacuation were evaluated subjectively in comparison to those from cases without evacuation. After each session, the residual intraluminal smoke was collected by a smoke testing device for objective evaluation. Results: Ten chemical compounds were detected. Smoke evacuation was achieved without collapse of the pneumostomach. Smoke was significantly reduced with the use of evacuation. Conclusions: Surgical smoke generated inside the gut lumen was potentially hazardous. Automatic evacuation was feasible and potentially useful in conjunction with SPACE technology. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Substantial differences in endoscopic strategy for gastric cancer exist between Western and Eastern countries, owing to clinicoepidemiological diversity, including differences in the prevalence of gastric cancer. This international multicenter study involved German and Japanese institutions and aimed to evaluate the influence of reviewers' clinical backgrounds on interpreting probe-based confocal laser endomicroscopy (pCLE) findings for diagnosis of superficial gastric lesions.Patients and Methods: 39 reviewers answered questionnaires about their clinical background and then reviewed 30 sets of white light endoscopy (WLE) and pCLE video clips via an online questionnaire. For each set of clips, reviewers were asked to classify lesions as neoplastic or non-neoplastic. RESULTS of video reviews were compared with the final histopathological diagnosis for each lesion. The accuracy of diagnosis based on WLE + pCLE was compared with that based on WLE alone for each aspect of clinical background.Results: The overall accuracy of diagnosis based on WLE + pCLE was higher than that based on WLE alone (73.93 % vs. 65.64 %, P = .0002). Outcomes of expert gastroenterologists were better than those of pathologists (P = .038 for WLE, P = .002 for WLE + pCLE) and outcomes of reviewers at Japanese institutions were better than those of reviewers at German institutions (P = .001 for WLE, P < .001 for WLE + pCLE).Conclusions: Reviewers from Japanese institutions and expert gastroenterologists performed well in the pCLE interpretation. Substantial experience in conventional endoscopy is important for interpreting pCLE images for the diagnosis of gastric cancer.University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; www.umin.ac.jp/ctr/index.htm) number UMIN 000013437). [ABSTRACT FROM AUTHOR]

There is increasing evidence that the expression of microRNA (miRNA) in cancer is associated with chemosensitivity but the mechanism of miRNA-induced chemoresistance has not been fully elucidated. The aim of this study was to examine the role of extracellular miRNA in the response to chemotherapy in esophageal cancer. First, serum expression of miRNAs selected by miRNA array was measured by quantitative reverse transcription-polymerase chain reaction in 68 patients with esophageal cancer who received cisplatin-based chemotherapy to examine the relationship between miRNA expression and response to chemotherapy. The serum expression levels of 18 miRNAs were different between responders and non-responders by miRNA array. Of these, high expression levels of miR-27a/b correlated with poor response to chemotherapy in patients with esophageal cancer. Next, in vitro assays were conducted to investigate the mechanism of miRNA-induced chemoresistance. Although transfection of miR-27a/b to cancer cells had no significant impact on chemosensitivity, esophageal cancer cells cultured in supernatant of miR-27a/b-transfected normal fibroblast showed reduced chemosensitivity to cisplatin, compared with cancer cells cultured in supernatant of normal fibroblast. MiR-27a/b-transfected normal fibroblast showed α-smooth muscle actin (α-SMA) expression, a marker of cancer-associated fibroblasts (CAF) and increased production of transforming growth factor-p (TGF-β). Chemosensitivity recovered after administration of neutralizing antibody of TGF-β to the supernatant transfer experiments. Our results indicated that miR-27a/b is involved in resistance to chemotherapy in esophageal cancer, through miR-27a/b-induced transformation of normal fibroblast into CAF. [ABSTRACT FROM AUTHOR]

Background In this study, we evaluated the technical feasibility of mucosal approximation of large ulcers via an endoscopic suturing system after endoscopic submucosal dissection (ESD), assessed the durability of these sutures, and compared this technique with serosal apposition of fullthickness gastric wall defects using the same device. Methods Post-ESD ulcers were closed with mucosal apposition in 7 pigs, and endoscopic fullthickness resection (EFTR) defects were closed with serosal apposition in 3 pigs. Pigs recovered for 1 week; they were then euthanized and necropsies were performed. Results Primary defect closure was achieved in 85.7% of the post-ESD closures and in 100% of the post-EFTR closures (p = 0.67). All pigs survived for 1 week. At necropsy, sutures had loosened in the post-ESD animals, although only minor deformity of the ulcer edges was observed in all repaired post-ESD ulcers. Meanwhile, all of the post-EFTR defect closures were sustained for 1 week. Conclusions Primary closure of post-therapeutic defects can be accomplished using the device. Inverted serosal apposition provides a more durable and reliable repair than everted mucosal apposition. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-II mRNA-binding protein-3 (IMP3) is an important factor in carcinogenesis, although its clinical significance in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study investigated the associations between IMP3 expression and the clinicopathological parameters. IMP3 expression was assessed in 191 resected ESCC specimens, and the associations between IMP3 expression in ESCC, the clinicopathological parameters and patient prognosis were examined. Using immunohistochemistry, 113 (59.2%) tumors were identified as IMP3-positive. IMP3 positivity correlated significantly with high pathological (p)Stage, pT stage and pN stage. The IMP3-positive patients exhibited a poorer prognosis compared with the IMP3-negative patients. In univariate analyses, histology [hazard ratio (HR), 1.94; 95% confidence interval (CI), 1.18-3.49; P=0.0082], pT (HR, 2.34; 95% CI, 1.55-3.62; P<0.0001), pN (HR, 2.85; 95% CI, 1.81-4.69; P<0.0001), lymphatic invasion (HR, 2.08; 95% CI, 1.26-3.70; P=0.0036), venous invasion (HR, 1.79; 95% CI, 1.21-2.64; P=0.0039), neoadjuvant chemotherapy (NAC) (HR, 2.01; 95% CI, 1.35-3.00; P=0.0005) and IMP3 expression (HR, 2.12; 95% CI, 1.40-3.29; P=0.0003) were significantly associated with overall survival. Using multivariate analyses, histology (HR, 1.87; 95% CI, 1.13-3.29; P=0.014), pN (HR, 2.19; 95% CI, 1.36-3.66; P=0.0010), NAC (HR, 1.88; 95% CI, 1.24-2.86; P=0.0028) and IMP3 expression (HR, 1.84; 95% CI, 1.18-2.93; P=0.0064) were significant prognostic factors. IMP3 may therefore be a prognostic factor for patients with ESCC who have undergone a curative resection. [ABSTRACT FROM AUTHOR]

Background and study aims: Steady pressure automatically controlled endoscopy (SPACE) is a new insufflation system that provides constant carbon dioxide (CO2) insufflation pressure during prolonged procedures. The system consists of an overtube, a surgical insufflator, and a newly developed leak-proof valve. The aims of this study were to validate the feasibility and safety of SPACE for esophageal endoscopic submucosal dissection (ESD). Patients and methods: This was a clinical phase I trial, involving 10 patients who underwent esophageal ESD. The primary end point was the rate of adverse events within 30 days (grade 0 to 4). Secondary end points were changes in partial pressure of carbon dioxide (PaCO2) and vital signs during ESD, completion rate of ESD, and degree of abdominal distension by patient assessment and radiographic grading. Results: All adverse events were Grade 2 or less. Mild PaCO2 elevation after ESD was noted; however, no associated symptoms were reported. The procedure was completed under SPACE alone in 8 of 10 patients. Minimal post-procedural bowel distension was observed. Conclusions: In this small pilot study, SPACE was feasible and appeared to be safe. Further study with larger case numbers is required to demonstrate efficacy and safety. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer associated with Crohn's disease (CD) is increasing in proportion to the number of patients with CD in Japan. There are two subtypes of colorectal cancer with CD: sporadic cancer and colitis-associated cancer. Early diagnosis of colitis-associated cancer is sometimes difficult; when colorectal cancer is found in patients with CD, both colitisassociated cancer and sporadic cancer should be kept in mind. Here, we describe a case of metachronous, colitis-associated rectal cancer that developed after the complete resection of an adenoma that became a sporadic adenocarcinoma in a patient with longstanding CD. To the best of our knowledge, this is the first report of colitis-associated cancer in a patient with CD after removal of a sporadic cancer. Case presentation We describe a 51-year old man with CD who had difficulty in defecation. A rectal polyp was detected and a transanal resection of the polyp was performed. A histopathological examination showed an adenoma with sporadic adenocarcinoma. After three years, a followup colonoscopy revealed a reddish, elevated lesion in the patient's rectum. A colonoscopic biopsy showed a signet ring cell carcinoma. We performed an abdominoperineal resection of the rectum and a bilateral pelvic lymph node dissection. A histopathological examination revealed a mucinous adenocarcinoma with signet ring cell carcinoma and lymph node metastasis. The patient received adjuvant chemotherapy with oral uracil 224 mg combined with tegafur 100 mg plus leucovorin. No signs of recurrence were noted at a follow-up 18 months after the third surgery and 60 months after the second surgery. [ABSTRACT FROM AUTHOR]

Background Hand-assisted laparoscopic surgery (HALS) has gained wide clinical acceptance as a practical alternative to laparoscopically assisted surgery (LAP) for the surgical treatment of complex colorectal diseases (e.g., ulcerative colitis and diverticulitis). However, its role in the further challenging operation for Crohn's colitis (i.e., subtotal or total colectomy) has yet to be established. This study aimed to evaluate the feasibility, safety, and potential benefit of HALS subtotal and total colectomy for Crohn's colitis. Methods The study reviewed 38 consecutive patients who underwent subtotal or total colectomy as their initial abdominal surgery for Crohn's extensive colitis (involvement of 3 or more colonic segments) between 1992 and 2006. The patients were divided into three groups (open, LAP, and HALS), and their background and postoperative data were retrospectively analyzed. Results The reviews included 14 open, 6 LAP, and 18 HALS cases. The groups were comparable in terms of age at surgery, gender, body mass index, extent and type of disease, indications, and procedures. The median operative time was significantly longer for LAP (330 min; range, 154-540 min) than for HALS (251 min; range, 165- 340 min) or open surgery (200 min; range, 172-315 min). The blood loss was significantly less with LAP (170 ml; range, 115-257 ml) and HALS (225 ml; range, 35-890 ml) than with open surgery (438 ml; range, 280-780 ml). No difference was seen in postoperative complications, and no mortality occurred in the series. Conclusions The findings showed that HALS subtotal and total colectomies are feasible and safe. The HALS procedure currently seems potentially beneficial for patients with extensive Crohn's colitis by reducing the operative time for laparoscopic surgery while retaining its less invasiveness. [ABSTRACT FROM AUTHOR]

Background Intraoperative endoscopy (IOE) is a useful adjunct during laparoscopic gastrointestinal (GI) surgery. However, one potential hazard of IOE is a prolonged bowel distension due to insufflated air, which may cause obstructed surgical exposure and increased postoperative abdominal pain. Recently, carbon dioxide (CO2), with its rapid absorptive nature, has been proven effective to minimize prolonged bowel distension in ambulatory/intraoperative colonoscopy. The objectives were to assess the feasibility, safety, and efficacy of CO2-insufflating upper GI IOE during laparoscopic surgery. Methods A historical comparison study was performed on the initial ten consecutive patients who underwent CO2- insufflating upper GI IOE (CO2-IOE) during laparoscopic surgery. The control group consisted of the past 12 consecutive patients who underwent conventional air-insufflating upper GI IOE (air-IOE) during laparoscopic surgery. The following parameters were compared between the two groups: (1) patient demographics; (2) feasibility (% completion of IOE); (3) safety (complications related to IOE, impacts on cardiopulmonary status, including systemic blood pressure, heart rate, and end-tidal CO2); (4) efficacy (postoperative residual intestinal gas, time to resume oral intake, and bowel movement). The amounts of post-IOE residual intestinal gas were evaluated and classified on the immediate postoperative abdominal radiographs in a blinded manner. Results Patient demographics were comparable between the two groups. IOE was completed in both groups without complications. Adverse effects on cardiopulmonary status were not observed during simultaneous intraperitoneal and intraluminal CO2 insufflation. In the air-IOE group, one patient was converted to open surgery because of inadequate surgical exposure from prolonged distension of the downstream bowel. The patients in the CO2-IOE group had significantly lower grade of postoperative bowel distension than the control group. Postoperative oral intake was resumed earlier in the CO2-IOE group. Conclusion CO2-insufflating upper GI IOE during laparoscopic surgery is feasible, safe, and has a practical advantage in minimizing post-IOE bowel distension compared with conventional air-insufflating upper GI IOE. [ABSTRACT FROM AUTHOR]

Abstract  An accurate preoperative staging is important for selecting an appropriate therapy for esophageal cancer. In particular, diagnosis of lymph node metastases influences the indication for radical surgery. [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely applied primarily as a useful tool for initial staging of esophageal cancer. However, false-negative cases sometimes make it difficult to select the appropriate treatment. We report two patients with esophageal cancer and PET-negative enlarged lymph node successfully diagnosed by laparoscopic sampling. This procedure did not only allow accurate histopathological staging, but also helped to select the optimal minimally invasive management. This technique can be recommended for patients with esophageal cancer in whom the diagnosis of enlarged lymph node cannot be confirmed by preoperative imaging. [ABSTRACT FROM AUTHOR]

Abstract  We describe a unique case of intra-abdominal textiloma (granuloma due to a retained foreign body), which mimicked a gastric tumor on preoperative imaging studies. A 78-year-old asymptomatic patient with a past history of a gastrectomy was referred for evaluation of an intra-abdominal mass lesion, which was incidentally observed on a computed tomography (CT) scan. Repeated CT with a higher resolution demonstrated a 5-cm heterogeneously enhanced mass with a distinct feeding artery. These findings were all compatible with a tumorous lesion originating in the gastric remnant, most likely gastric gastrointestinal stromal tumor. A diagnosis of textiloma was immediately made during surgery, and it was confirmed pathologically postoperatively. The feeding artery that appeared on CT images, which was a major reason for the false diagnosis, was considered to have resulted from a slow but continuous inflammation reaction around the retained surgical sponge. Surgeons should therefore always take the possibility of textilomas into consideration even with typical tumorous characteristics on preoperative imaging studies, especially in patients with a history of prior abdominal surgery. [ABSTRACT FROM AUTHOR]

We performed laparoscopic liver biopsy in a 10-year-old girl with acute myelocytic leukemia and coagulopathy. Each biopsy was taken under laparoscopic ultrasound (LUS) guidance, and hemostasis was achieved with an argon beam coagulator (ABC). These instruments were introduced through one 10/12-mm port, which also allowed the insertion of surgical gauze for direct compression. By using LUS, ABC, and one full-sized working port, laparoscopic liver biopsy becomes a viable and safer alternative, even for children with coagulopathy. [ABSTRACT FROM AUTHOR]