Covert stroke after non-cardiac surgery: a prospective cohort study.

BACKGROUND: Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery. METHODS: We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke. RESULTS: We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5-17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12). CONCLUSIONS: This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes. CLINICAL TRIAL REGISTRATION: NCT01369537.

Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model.

BACKGROUND: Mesenchymal stem cells are proposed to facilitate repair of organ injuries. The aim of this study was to investigate whether local injection of mesenchymal stem cells could accelerate healing of sutured gastric perforations. METHODS: Sutured gastric perforations in rats were treated either with local injection of mesenchymal stem cells (injected MSC group) or by topically spraying with fibrin glue containing mesenchymal stem cells (sprayed MSC group). Controls were treated by local injection of saline or topical spray of fibrin glue without mesenchymal stem cells. Healing of sutured gastric perforations was assessed on days 3, 5 and 7. RESULTS: Local injection of mesenchymal stem cells significantly promoted the healing of gastric perforations, with the highest pneumatic bursting pressure (mean(s.e.m.) 112·3(30·2) mmHg on day 5 versus 71·2(17·4) mmHg in saline controls; P = 0·001), minimal wound adhesions, and lowest incidence of wound dehiscence (3, 6, 5 and 1 animal on day 5 in control, fibrin, sprayed MSC and injected MSC groups respectively; n = 10 per group) and abdominal abscess (2, 2, 1 and no animals respectively on day 5). Histological examination showed that gastric perforations in the injected MSC group displayed reduced inflammation, and increased granulation and re-epithelialization. Sutured gastric perforations in the injected MSC group showed decreased expression of interleukin 6, and increased expression of transforming growth factor ß1 and epithelial proliferating cell nuclear antigen, compared with the other groups. CONCLUSION: Local injection of mesenchymal stem cells was more effective than topical application, and enhanced the healing of sutured gastric perforations by an anti-inflammatory process, enhanced cellular proliferation and earlier onset of granulation. Surgical relevance Abnormal healing of gastric perforation may cause morbidity and increase the risk of death. Adipose tissue-derived mesenchymal stem cells have been found to promote the healing of organ injuries through cellular differentiation and secretion of cytokines that stimulate cellular proliferation and angiogenesis, and suppress inflammation. This study explored the therapeutic potential of such mesenchymal stem cells for promotion of the healing of sutured gastric perforations. Mesenchymal stem cells delivered by local injection significantly enhanced the healing of gastric perforations with reduced severity of wound adhesion, and a decreased incidence of wound dehiscence and abdominal abscess. The increased expression of transforming growth factor ß1, proliferating cell nuclear antigen and reduced level of interleukin 6 provide evidence for enhancement of the healing process. Engrafted mesenchymal stem cells expressed α-smooth muscle actin as a marker of myofibroblasts. This preclinical study indicates that local injection of allogeneic adipose tissue-derived mesenchymal stem cells may have a potential therapeutic role in enhancing the healing of peptic ulcer disease and prevention of ulcer-related complications.

Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial.

BACKGROUND: The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. PATIENTS AND METHODS: Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. RESULTS: Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. CONCLUSIONS: Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.

Laparoscopic Heller's cardiomyotomy achieved lesser recurrent dysphagia with better quality of life when compared with endoscopic balloon dilatation for treatment of achalasia.

Achalasia is a rare primary motility disorder of esophagus; treatments include endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC). This study compared EBD versus LC for treatment of achalasia with focus on quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux disease. This was a retrospective cohort study of all patients diagnosed with achalasia older than 16 treated with either EBD or LC from January 1998 to April 2008. Patients' demographic data, comorbidities, postintervention GERD symptoms, QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to resumption of diet were collected. Sixty-eight patients were recruited into the study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of patients treated with EBD developed post-treatment gastroesophageal reflux symptoms (60.5% vs. 43.8%) when compared with LC, although statistically insignificant (P= 0.34). Patients treated with balloon dilatation had a greater percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0-3]). Although EBD is associated with a quicker perioperative recovery, LC accomplished a better QoL, lower incidence of recurrence of dysphagia, and need of reintervention after treatment for achalasia.

Precut sphincterotomy using insulated angulotome.

A newly designed insulated angulotome was evaluated in a series of patients in whom biliary cannulation using conventional methods had failed and who required precut sphincterotomy. The new device consists of an insulated glass tip to prevent excessive electrocautery flow, and angulation to facilitate elevation of the papillary roof on cutting. A prospective series of patients with cholangitis or obstructive jaundice with failed biliary cannulation were recruited. The success of cannulation and complications following endoscopic retrograde cholangiopancreatography were analyzed. A total of 13 patients underwent precut sphincterotomy using the insulated angulotome. The immediate success of gaining biliary access after failed cannulation was 100 %. The mean size of the common bile duct on ultrasonography was 8.1 mm. The mean time to achieve biliary cannulation was 9 minutes 4 seconds, and there was no perforation or bleeding. This case series showed that precut sphincterotomy with the insulated angulotome can be safely performed without major complications.

Endoscopic submucosal dissection used for treating early neoplasia of the foregut using a combination of knives.

BACKGROUND: Endoscopic submucosal dissection (ESD) has emerged as a novel technique for achieving en bloc resection for early esophageal or gastric carcinoma limited to the mucosa. The authors report their experience with a combination of various devices to treat early neoplasia of the foregut using the ESD technique. METHODS: In this prospective case series, ESD was performed for early esophageal or gastric carcinoma limited to the mucosa. These lesions were staged by endoscopic ultrasonography before resection. Magnifying endoscopy and chromoendoscopy were used to locate the tumor and define the margin. The resection was accomplished with submucosal dissection using the insulated tip knife, the hook knife, and the triangular tip knife. The resected specimen was examined systematically for the lateral and deep margins. RESULTS: From January 2004 to March 2006, ESD was performed to manage 30 cases of early gastric or esophageal carcinoma. For 29 of these patients, R0 resection was successfully achieved. The mean operating time was 84.6 min. One patient experienced reactionary hemorrhage 12 h after resection, which was controlled endoscopically. There was no perforation. Most of the circumferential mucosal incisions were performed using the insulated tip knife (76.6%), whereas submucosal dissection was accomplished with a combination of various knives. One of the specimens showed involvement of the lateral margin, whereas another patient had two areas of new early gastric cancer 6 months after the initial procedure. These patients received salvage laparoscopically assisted gastrectomy. CONCLUSIONS: Endoscopic submucosal dissection to manage early neoplasia of the foregut can be achieved safely and effectively with a combination of knives.

Adjuvant chemoradiation for gastric cancer: experience in the Chinese population.

AIMS: The role of adjuvant chemoradiation for gastric cancer after curative R0 gastrectomy was first established by the US Intergroup 0116 study. Although confirmatory studies are in progress, few data are available regarding its application to the Chinese population. We describe our radiotherapy technique and report the treatment results in Hong Kong. MATERIALS AND METHODS: This was a single centre retrospective study on 63 Chinese patients who underwent adjuvant chemoradiation for gastric adenocarcinoma between June 2000 and December 2004. The treatment protocol was based on that of the Intergroup study. Computed tomography planned anteroposterior opposing field arrangement and treatment under breath hold at deep inspiration position were adopted. RESULTS: In total, 63 patients, mean age 50 years, with gastric cancer stage IB to limited metastatic IV disease were analysed. The median follow-up time was 27.2 months. The relapse-free survival and overall survival at 3 years were 50 and 54%, respectively. The recurrence pattern was dominated by distant failure and only one patient developed isolated locoregional recurrence. Of the 10 patients who had positive microscopic surgical margins after surgery, seven had recurred and died. On multivariate analysis, margin status was the only significant prognosticator for survival. Thirty per cent of patients experienced grade 3 or above acute toxicity (24% haematological, 14% gastrointestinal) and one patient died of neutropenic sepsis. There was one case of grade 3 late toxicity. CONCLUSIONS: The outcome after adjuvant chemoradiation for gastric cancer seemed to be favourable, with manageable toxicities, in the Chinese population. Locoregional failure was uncommon. Patients with microscopic surgical margin involvement had a very high failure rate despite adjuvant chemoradiation.

Motion compensated controller for a tendon-sheath-driven flexible endoscopic robot.

BACKGROUND: A tendon-sheath system (TSS) has the advantages of being relatively compact in size, flexible and low cost, and therefore is favoured in building flexible endoscopic robots to pass through long and tortuous human lumen. TSS, however, is prone to nonlinear behaviors such as backlash, hysteresis and direction dependent properties. A compensation technique is required to improve its positioning performance. METHODS: Tension and elongation models of TSS are analyzed. A feedforward motion compensation controller is designed to compensate the asymmetric backlash behavior of the TSS in real time. RESULTS: Motion tracking experiments were conducted on a TSS driven two DOFs continuum manipulator. The results showed that using the proposed compensation methods, tracking error can be reduced by 74%. CONCLUSIONS: The proposed compensation method is useful for controlling flexible continuum robots, which are anticipated to have emerging roles in assisting surgeons to perform the increasingly technically challenging endoscopic procedures. Copyright © 2016 John Wiley & Sons, Ltd.

REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype.

REC8 meiotic recombination protein (REC8) was found to be preferentially methylated in gastric cancer (GC) using promoter methylation array. We aimed to elucidate the epigenetic alteration and biological function of REC8 in GC. REC8 was downregulated in 100% (3/3) of Epstein-Barr virus (EBV)-positive and 80% (8/10) of EBV-negative GC cell lines by promoter methylation, but the expression could be restored through demethylation treatment. Protein expression of REC8 was significantly lower in human primary gastric tumors than in adjacent non-tumor tissues. A negative correlation between methylation and mRNA expression of REC8 was observed in 223 gastric samples of The Cancer Genome Atlas study (r=-0.7018, P<0.001). The methylation level (%) of the REC8 promoter was significantly higher in EBV-positive gastric tumors than in EBV-negative gastric tumors, as shown by bisulfite genomic sequencing (77.6 (69.3-80.5) vs 51.4 (39.5-62.3), median (interquartile range); P<0.001); methylation levels in both subtypes of tumors were significantly higher than in normal stomach tissues (14.8 (4.2-24.0)) (both P<0.001). Multivariate analysis revealed that REC8 methylation was an independent factor for poor survival in GC patients (hazard ratio=1.68, P<0.05). REC8 expression significantly suppressed cell viability, clonogenicity and cell cycle progression; it induced apoptosis and inhibited migration of AGS-EBV (EBV-positive) and BGC823 (EBV-negative) GC cells, and it suppressed tumorigenicity in nude mice. In contrast, knockdown of REC8 in gastric epithelial immortalized GES-1 cells significantly increased cell viability, clonogenicity and migration ability. The tumor-suppressive effect of REC8 is mediated at least in part by the downregulation of genes involved in cell growth (G6PD, SLC2A1, NOL3, MCM2, SNAI1 and SNAI2), and the upregulation of apoptosis/migration inhibitors (GADD45G and LDHA) and tumor suppressors (PinX1, IGFBP3 and ETS2). In conclusion, REC8 is a novel tumor suppressor that is commonly downregulated by promoter methylation in GC, especially in the EBV-associated subtype. Promoter methylation of REC8 is an independent risk factor for the shortened survival of GC patients.

Routine early laparoscopic cholecystectomy for acute cholecystitis after conclusion of a randomized controlled trial.

BACKGROUND: The aim of this retrospective review was to assess the clinical outcomes of laparoscopic cholecystectomy for acute cholecystitis since the conclusion of a randomized controlled trial in 1997. METHODS: Records of all patients admitted for acute cholecystitis in whom early laparoscopic cholecystectomy was attempted between July 1997 and December 2004 were reviewed. RESULTS: A total of 209 patients were recruited to this study. Forty-three surgeons performed the procedures. The conversion rate increased significantly in the early period after the trial from 21 per cent to 42 per cent (39 of 92 patients) and decreased significantly to 24 per cent (13 of 54 patients) in the later period. The proportion of operations performed by higher surgical trainees increased significantly from 17 per cent in the early period to 56 per cent in the later period. This increase was associated with a fall in conversion rate without any significant increase in duration of operation or complication rate. CONCLUSION: This study has demonstrated that the results achieved in a randomized trial can be translated into clinical practice by the entire surgical unit. A structured training programme with the inclusion of an experienced surgeon assisting both trainees and specialists should minimize this learning curve.

Validation of the quality of histological images obtained of fresh and formalin-fixed specimens of esophageal and gastric mucosa by laser-scanning confocal microscopy.

BACKGROUND AND STUDY AIMS: We have previously reported the success of a method of virtual histology using laser-scanning confocal microscopy (LCM) in vitro on untreated fresh specimens obtained from the gastrointestinal mucosa. In the present study, we aimed to apply LCM to both fresh and formalin-fixed specimens, without additional treatment, in order to validate and compare the quality of the images obtained. METHODS: We obtained 18 specimens from 11 patients, either by endoscopic biopsy or following surgical resection. First, we observed the fresh, saline-immersed specimen with LCM using the Fluroview microscope (Olympus Co. Ltd., Tokyo, Japan). We then fixed the specimen with formalin and obtained further LCM images 1 hour, 3 hours, and 24 hours after fixation. Three independent observers observed the images and were asked to assess the origin of the samples, the treatment of the samples, the time after formalin fixation, and whether they showed benign or malignant lesions. We used kappa statistics to compare the agreement among the three observers in each of these four areas of interest. RESULTS: Between January and March 2003, we obtained 191 LCM images from 18 specimens. Thirty images were randomly selected for observation. The overall accuracy for differentiating between esophagus and stomach specimens was 96.6 %. The accuracy of differentiating normal from cancerous lesions was 92.2 %. The differentiation between saline-immersed and formalin-fixed specimens was 59.7 % accurate and the assessment of the time interval after formalin fixation was only 37.3 % accurate. The kappa statistics showed that there was strong interobserver agreement on the differentiation of specimen origin and of cancerous from benign lesions. However, there was no agreement among the observers on the method of specimen preparation or on the estimated time interval after formalin fixation. CONCLUSIONS: We concluded that images obtained from fresh specimens using LCM were of a quality good enough to make an accurate diagnosis of upper gastrointestinal carcinoma.

Predictors of peptic ulcer rebleeding after scheduled second endoscopy: clinical or endoscopic factors?

BACKGROUND AND STUDY AIMS: In a previous study we demonstrated the efficacy of second-look endoscopy with therapy within 16 - 24 hours after index endoscopy in reducing major recurrent peptic ulcer bleeding. In this study, we sought to identify factors that might predict further rebleeding after this scheduled second-look endoscopy. PATIENTS AND METHODS: We studied 249 patients (181 men, 68 women) with acute bleeding peptic ulcers who were treated at the United Christian Hospital, Hong Kong from 1999 to 2002 and who underwent a scheduled second endoscopy. Those patients who developed rebleeding after the second endoscopy were evaluated, and possible predictive factors for rebleeding were analyzed using a logistic regression model. RESULTS: Of the 249 patients who underwent scheduled second-look endoscopy, 17 patients (6.8 %) developed rebleeding: seven of these patients were treated by another endoscopic therapy; ten patients required surgery. The overall mortality rate was 3.1 %. A logistic regression analysis performed on the possible predictive factors for rebleeding found that the following factors were associated with a significant risk of further rebleeding after scheduled second endoscopy: American Society of Anesthesiologists (ASA) grade III or grade IV status (odds ratio 3.81, 95 % CI 1.27 - 11.44), ulcer size greater than 1.0 cm (odds ratio 4.69, 95 % CI 1.60 - 13.80), and a finding of persistent stigmata of recent hemorrhage at the scheduled second endoscopy (odds ratio 6.65, 95 % CI 2.11 - 20.98). CONCLUSIONS: Endoscopic factors, including large ulcer size and the persistence of endoscopic stigmata of recent hemorrhage are important predictors for recurrent bleeding after scheduled second endoscopy.

Effect of scheduled second therapeutic endoscopy on peptic ulcer rebleeding: a prospective randomised trial.

AIM: Recurrent bleeding after initial haemostasis is an important factor that directly relates to the outcome in the management of peptic ulcer bleeding. Conflicting reports have been published concerning the effectiveness of scheduled second therapeutic endoscopy on ulcer rebleeding. We investigate the use of scheduled second endoscopy with appropriate therapy on peptic ulcer rebleeding. METHODS: From August 1999 to January 2001, we prospectively randomised patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of acute bleeding, visible vessel, or adherent clot into two groups. Endoscopic therapy was standardised to initial epinephrine injection and subsequent heater probe application. The study group (n = 100) received scheduled second endoscopy 16-24 hours after initial haemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. The control group (n = 94) were observed closely. Those patients that developed rebleeding in either group underwent operation if further endoscopic therapy failed. Outcome measures included ulcer rebleeding, transfusion, duration of stay, and mortality. RESULTS: After initial endoscopic haemostasis, 194 eligible patients were randomised into two groups. Thirteen patients in the control group developed recurrent bleeding within 30 days while five patients in the study group sustained recurrent bleeding (p = 0.0314) (relative risks 0.33, 95% confidence interval 0.1-0.96). The number of patients that required surgery for recurrent bleeding was six in the control group and one in the study group (p = 0.05). There was no difference in duration of hospital stay, transfusion, or mortality between the two groups. CONCLUSIONS: A scheduled repeat endoscopy with appropriate therapy 16-24 hours after initial endoscopic haemostasis reduces the number of cases of recurrent bleeding.