Radiofrequency ablation compared with laparoscopic adrenalectomy for aldosterone-producing adenoma.

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was a retrospective comparative study in patients with aldosterone-producing adenoma undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA between 2004 and 2012. Short-term outcomes and long-term resolution rates of primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy) were evaluated. RESULTS: Some 63 patients were included, 27 in the laparoscopic adrenalectomy group and 36 in the RFA group. RFA was associated with shorter duration of operation (median 12 versus 124 min; P < 0·001), shorter hospital stay (2 versus 4 days; P < 0·001), lower analgesic requirements (13 of 36 versus 23 of 27 patients; P < 0·001) and earlier resumption of work (median 4 versus 14 days; P = 0·006). Morbidity rates were similar in the two groups. With median follow-up of 5·7 (range 1·9-10·6) years, resolution of primary aldosteronism was seen in 33 of 36 patients treated with RFA and all 27 patients who had laparoscopic adrenalectomy (P = 0·180). Hypertension was resolved less frequently after treatment with RFA compared with laparoscopic adrenalectomy (13 of 36 versus 19 of 27 patients; P = 0·007). Hypokalaemia was resolved in all patients. CONCLUSION: For patients with aldosterone-producing adenoma the efficacy of resolution of primary aldosteronism and hypertension was inferior after treatment with RFA compared with laparoscopic adrenalectomy.

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.

Magnetotransport at domain walls in BiFeO3.

Domain walls in multiferroics can exhibit intriguing behaviors that are significantly different from the bulk of the material. We investigate strong magnetoresistance in domain walls of the model multiferroic BiFeO3 by probing ordered arrays of 109° domain walls with temperature- and magnetic-field-dependent transport. We observe temperature-dependent variations in the transport mechanism and magnetoresistances as large as 60%. These results suggest that by locally breaking the symmetry of a material, such as at domain walls and structural interfaces, one can induce emergent behavior with properties that deviate significantly from the bulk.

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.

In vivo gamma-aminobutyric acid and glutamate levels in people with first-episode schizophrenia: A proton magnetic resonance spectroscopy study.

BACKGROUND: Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic neurons. In this study, levels of GABA, Glx (summation of glutamate and glutamine), and other metabolites in the anterior cingulate cortex were measured and compared between first-episode schizophrenia subjects and healthy controls (HC). Diagnostic potential of GABA and Glx as upstream biomarkers for schizophrenia was explored. METHODS: Nineteen first-episode schizophrenia subjects and fourteen HC participated in this study. Severity of clinical symptoms of patients was measured with Positive and Negative Syndrome Scale (PANSS). Metabolites were measured using proton magnetic resonance spectroscopy, and quantified using internal water as reference. RESULTS: First-episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and increased Glx and choline (Cho), compared to HC. No significant correlation was found between metabolite levels and PANSS scores. Receiver operator characteristics analyses showed Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophrenia patients from HC. Combined model of both GABA and Glx revealed the best sensitivity and specificity (89.5%, 100%). CONCLUSION: This study simultaneously showed reduction in GABA and elevation in Glx in first-episode schizophrenia subjects, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho might indicate increased membrane turnover; whereas reduced mI might reflect dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed their diagnostic potential for schizophrenia.

Preoperative endoscopic retrograde cholangiopancreatographic treatment of complicated choledochal cysts in children: a retrospective case series.

We report our experience with endoscopic retrograde cholangiopancreatography-(ERCP-)based interventions in children with complicated choledochal cysts that are refractory to conservative management. Between 1999 and 2006, 42 children (12 boys, 30 girls; median age 3 years, range 2-14.5 years) were admitted for surgical treatment of choledochal cysts. Seven of these patients (16.7%; one boy, six girls; median age 3 years, range 2-12 years) showed signs of complicated choledochal cysts, and presented with pancreatitis/cholangitis (n = 4) and obstructive jaundice (n = 3). The anatomical classification of the cysts was type Ic (n = 3), type If (n = 3), and type IV (n = 1). ERCP was successfully performed in 6/7 patients, and therapeutic interventions included removal of debris (n = 3), sphincterotomy (n = 3), and stent placement (n = 4). One patient required blood transfusion for post-sphincterotomy bleeding. The patient in whom the ERCP failed underwent ultrasound-guided percutaneous transhepatic biliary drainage. Definitive surgery was performed after a median interval of 10 days (range 7-68 days) after the ERCP intervention.

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.

Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial.

BACKGROUND: A previous single-centre study showed that lower oesophageal sphincter electrical stimulation therapy (LES-EST) in gastro-oesophageal reflux disease (GERD) patients improves reflux symptoms and decreases oesophageal acid exposure. AIM: To evaluate safety and efficacy of LES-EST in GERD patients with incomplete response to proton pump inhibitors (PPIs) in a prospective, international, multicentre, open-label study. METHODS: GERD patients, partially responsive to PPIs, received LES-EST. GERD health-related quality of life (GERD-HRQL), daily symptom diaries, quality of life scores, oesophageal acid exposure, and LES resting and residual pressure were measured before and after initiation of LES-EST. Stimulation sessions were optimised based on residual symptoms and oesophageal acid exposure. RESULTS: Forty-four patients were enrolled and 6-month data from 41 patients are available. Hiatal repair was performed in 16 patients. One device-related, one procedure-related and one unrelated severe adverse event were reported. GERD-HRQL improved from 31.0 (IQR 26.2-36.8) off-PPI and 16.5 (IQR 9.0-22.8) on-PPI to 4 (IQR 1-8) at 3-month and 5 (IQR 3-9) at 6-month follow-up (P < 0.0001 vs. on- and off-PPI). Oesophageal acid exposure (pH < 4.0) improved from 10.0% (IQR 7.5-12.9) to 3.8% (IQR 1.9-12.3) at 3 months (P = 0.0027) and 4.4% (IQR 2.2-7.2) at 6 months (P < 0.0001). CONCLUSIONS: These interim results show an acceptable safety record of LES-EST to date, combined with good short-term efficacy in GERD patients who are partially responsive to PPI therapy. A remarkable reduction in regurgitation symptoms, without the risk of intervention-requiring dysphagia may prove to be an advantage compared with other anti-reflux procedures. ClinicalTrials.gov Identifier: NCT01574339.

Conservative approach is feasible in the management of acute diverticulitis of the right colon.

BACKGROUND: Acute diverticulitis of the caecum and ascending colon is uncommon. Controversies abound as regards the optimal surgical treatment, ranging from appendectomy, diverticulectomy to right hemicolectomy. The aim of the present paper was to review treatment strategy followed by a critical appraisal. METHODS: The case notes of 30 patients with acute diverticulitis of the right colon who were treated at the United Christian Hospital, Hong Kong from 1992 to 1998 were systematically reviewed. The data were subjected to statistical analysis. RESULTS: The median age was 34 years, with a male:female ratio of 1:1.15. All patients presented with acute right lower abdominal pain and localized rebound tenderness. All were diagnosed preoperatively as having appendicitis. The mean duration of symptoms was 2 days (range: 1-6 days). Two treatment groups were identified. Group A (n = 16; 53%) received appendicectomy alone, while group B (n = 14; 47%) underwent diverticulectomy in addition to appendicectomy, including one patient with perforated diverticulitis. Overall, there was no procedure-related morbidity or mortality. Both groups received a similar duration of broad-spectrum antibiotics. All the patients were interviewed by phone after operation to detect any recurrence of symptoms, with a median follow-up interval of 34 months (range: 11-78 months). There was no recurrence of symptoms in group A, which received appendicectomy and antibiotics. The only difference was operative time. CONCLUSION: For non-perforated diverticulitis of the right colon, appendicectomy and intravenous antibiotics without diverticulectomy is the preferred treatment strategy.