The effect of Andrographis paniculata water extract on palliative management of metastatic esophageal squamous cell carcinoma-A phase II clinical trial.

Patients with metastatic esophageal squamous cell carcinoma (ESCC) have a grave prognosis with limited life expectancy. Here, a phase II clinical trial was conducted to investigate the effect of Andrographis paniculata (AP) on the palliative care of patients with metastatic ESCC. Patients with metastatic or locally advanced ESCC deemed unfit for surgery, and who have already completed palliative chemotherapy or chemoradiotherapy or are not fit for these treatments, were recruited. These patients were prescribed AP concentrated granules for 4 months. They also received clinical and quality of life assessments for clinical response, as well as positron emission tomography-computed tomography at 3 and 6 months after AP treatment for the assessment of tumor volume. Furthermore, the change in gut microbiota composition after AP treatment was studied. From the results, among the 30 recruited patients, 10 completed the entire course of AP treatment, while 20 received partial AP treatment. Patients who completed the AP treatment achieved significantly longer overall survival periods with the maintenance of the quality of life during the survival period when compared to those who could not complete AP treatment. The treatment effect of AP also contributed to the shift of the overall structure of gut microbiota for ESCC patients towards those of healthy individuals. The significance of this study is the establishment of AP as a safe and effective palliative treatment for patients with squamous cell carcinoma of the esophagus. To the best of our knowledge, this is the first clinical trial of AP water extract in esophageal cancer patients demonstrating its new medicinal use.

Alterations in gut microbiota of esophageal squamous cell carcinoma patients.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer worldwide. Patients with ESCC display an altered esophageal microbiota compared with healthy individuals; however, little is known about the gut microbiota in ESCC. METHODS: Here, we characterized the fecal microbiota of 15 ESCC patients and 16 healthy control subjects using 16S rRNA gene sequencing. RESULTS: After controlling for potential confounders, significant alterations in both taxonomic and functional composition of the gut microbiota in ESCC patients were observed. By contrast, alpha diversity of the gut microbiota did not significantly differ between the cases and controls. We observed an enrichment of potentially pro-inflammatory and/or carcinogenic bacteria, such as Butyricimonas, Veillonella, and Streptococcus, and a depletion of butyrate-producing and/or potentially anti-inflammatory bacteria, such as Butyricicoccus, Lachnospiraceae NK4A136 group, and Eubacterium eligens group, in the gut microbiota of ESCC patients. The log-ratios of Streptococcus to Butyricicoccus and Streptococcus to Lachnospiraceae NK4A136 group of the gut microbiota were identified as potential diagnostic biomarkers for ESCC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.863 (95% confidence interval: 0.707-1.000) and 0.825 (0.673-0.977), respectively. The diagnostic performance of both microbial biomarkers was validated in another ESCC cohort. CONCLUSIONS: This pilot study has revealed an altered gut microbiota in ESCC patients and has paved the way for large-scale prospective cohort studies to examine the causative relationship between ESCC and gut dysbiosis.

Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. BACKGROUND: Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. METHODS: This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. RESULTS: Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. CONCLUSION: Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.

Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside (with video).

BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. OBJECTIVE: This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. DESIGN: Preclinical animal study and prospective clinical study. PATIENTS: Consecutive patients diagnosed with achalasia with high-resolution manometry. INTERVENTIONS: POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. MAIN OUTCOME MEASUREMENTS: Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. RESULTS: Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. LIMITATION: Small sample size. CONCLUSIONS: POEM is a feasible, safe, and effective treatment for achalasia.

Endoscopic submucosal dissection (ESD) compared with gastrectomy for treatment of early gastric neoplasia: a retrospective cohort study.

INTRODUCTION: This study aims to compare perioperative outcomes and oncological clearance of endoscopic submucosal dissection (ESD) versus gastrectomy for treatment of early gastric cancer (EGC). METHODS: This is a retrospective cohort study including all cases of EGC or severe dysplasia treated at a university-affiliated hospital from 1993 to 2010. Preoperative endoscopic ultrasound and image-enhanced endoscopy were employed to determine depth of invasion. Clinical outcomes including baseline demographics, pathology, postoperative complication, and hospital stay, as well as 3-year survival were compared. RESULTS: From 1993 to 2010, 114 patients with severe dysplasia or EGC were treated: 40 of them received gastrectomy, while 74 received ESD. There was no difference in age, gender, comorbidity or American Society of Anesthesiologists grade between the two groups. Of patients in the gastrectomy group, 92.5% presented with symptoms as compared with 27.0% of those treated by ESD (p < 0.001). More patients in the ESD group had atrophic gastritis (31.1 vs 10%; p = 0.009) and intestinal metaplasia (68.9 vs 55.0%; p = 0.04). Patients treated by gastrectomy sustained longer operative time [265 (150-360) min] when compared with ESD [89.6 (45-360) min; p < 0.001]. They also had longer median hospital stay [9.9 (6-26) days vs 3.0 (2-10) days; p < 0.001]. There was no perioperative mortality, but the overall complication rate was significantly higher in the gastrectomy group. The 3-year survival rate was 94.6% for ESD and 89.7% for gastrectomy group (log-rank test, p = 0.44). CONCLUSIONS: ESD achieved similar oncological outcomes when compared with radical gastrectomy for treatment of EGC. Patients receiving ESD had better perioperative outcomes in terms of operative time, complication rate, and hospital stay.

Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases.

OBJECTIVES: Despite advances in endoscopic and pharmacological treatment for peptic ulcer bleeding (PUB), mortality remains at 5-10% worldwide. Our aim was to investigate the causes of death in a prospective cohort of PUB in a tertiary referral center. METHODS: Between 1993 and 2005, all patients with upper gastrointestinal bleeding (UGIB) admitted to the Prince of Wales Hospital were prospectively registered. Demographic data, characteristics of ulcer, and pharmacological, endoscopic, and surgical therapy, were documented. Mortality cases were classified as (A) bleeding-related death (A1: uncontrolled bleeding, A2: within 48 h after endoscopy, A3: during surgery for uncontrolled bleeding, A4: surgical complications or within 1 month after surgery, and A5: endoscopic related mortality) or (B) non-bleeding-related death (B1: cardiac causes, B2: pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure, and B5: terminal malignancy). RESULTS: In all, 18,508 cases of UGIB were enrolled; among them, 10,428 cases from 9,375 patients were confirmed to have PUB, and 577 (6.2%) patients died. There were significantly more patients who died of non-ulcer bleeding causes (79.7%) than bleeding causes (18.4%). The mean (s.d.) age of those who died of bleeding-related causes was higher (75.4 (12.6) years) than that of those who died of non-bleeding causes (71.7 (13.1) years) (P=0.010). Most bleeding-related deaths occurred when immediate control of bleeding failed (29.2%) or when patients died within 48 h after endoscopic therapy (25.5%). Among those who died of non-bleeding-related causes, multiorgan failure (23.9%), pulmonary conditions (23.5%), and terminal malignancy (33.7%) were most common. CONCLUSIONS: The majority of PUB patients died of non-bleeding-related causes. Optimization of management should aim at reducing the risk of multiorgan failure and cardiopulmonary death instead of focusing merely on successful hemostasis.

Surgical salvage of bleeding peptic ulcers after failed therapeutic endoscopy.

BACKGROUND: The approach to salvage surgery after failed endoscopic therapy for a bleeding peptic ulcer is controversial. We aimed to compare the outcomes of salvage surgery after failed endoscopic therapy for bleeding peptic ulcers over a 10-year period. METHODS: Patients receiving salvage surgery for bleeding peptic ulcers were divided into 2 cohorts, the 1st from 1993 to 1998 and the 2nd from 1999 to 2004. The type of salvage surgery was defined as minimal if ulcer plication or an ulcerectomy was performed, and definitive if the patient received a vagotomy or gastrectomy. RESULTS: One hundred and twenty-three patients received salvage surgery in the 1st cohort, while 42 patients received surgical hemostasis for the bleeding peptic ulcer in the 2nd cohort. Patients in the 2nd cohort consisted of a larger proportion of in-hospital bleeders (cohort 1: 12.2%, cohort 2: 42.9%; p < 0.005) and had a significantly higher proportion of comorbidities. A larger number of patients received minimal surgery in cohort 2 (cohort 1: 42.3%, cohort 2: 73.8%; p < 0.005). CONCLUSIONS: With advances in therapeutic endoscopy, patients who developed failed endoscopic hemostasis are likely to be poor surgical candidates with multiple comorbidities. The approach to salvage surgery has inclined towards minimal surgery to hasten surgical hemostasis among these fragile patients.

Laparoscopic sleeve gastrectomy in ethnic obese Chinese.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity in ethnic Chinese in Hong Kong. METHODS: Seventy consecutive Chinese patients (49 females; mean age 34.7+/-8.8 [range 18-56] years) received LSG for the treatment of obesity from May 2006 to Nov 2007 as a stand-alone procedure for weight reduction. Mean baseline body weight (BW) and body mass index (BMI) were 108.9+/-22.1 kg (range 71.0-164.9 kg) and 40.7+/-7.8 kg/m(2) (range 27.4-68.4 kg/m(2)), respectively. Outcome measures were collected and assessed in a prospective manner. RESULTS: All procedures were performed laparoscopically with no conversion. There was neither mortality nor any postoperative complications that required reoperation. Major complication occurred in two patients (2.9%; esophagogastric junction [EGJ] leak and stomach tube stricture). Mean follow-up was 7.1+/-5.0 months. Mean procedure time was 90.6+/-39.4 min, and mean hospital stay was 3.8+/-2.3 days. Mean BMI loss was 6.3+/-2.5, 9.0+/-3.4 and 12.3+/-4.5 kg/m(2) at 3, 6, and 12 months. Mean percent of excess BW loss was 48.5+/-28.4, 69.7+/-31.7, and 63.5+/-29.4 at 3, 6, and 12 months. CONCLUSION: LSG is safe and effective in achieving significant weight loss in obese ethnic Chinese patients.

A major outbreak of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. METHODS: From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. RESULTS: There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). CONCLUSIONS: SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort.

Intragastric balloon in ethnic obese Chinese: initial experience.

BACKGROUND: We evaluated the effectiveness and safety of intragastric balloon (IGB) for the treatment of obesity in ethnic Chinese in Hong Kong. METHODS: 15 Chinese patients (10 females; median age 40 years (range 21-58)) completed IGB treatment over a 10-month period since November 2004. Median baseline body weight (BW) and BMI were 100.1 (range 78.5-170.3) kg and 39.4 (range 29.6-56.9) kg/m2 respectively. Coexistent obesity-related morbidities were present in 80% of patients. The Bioenterics Intragastric Balloon (BIB) was employed, and all placement and removal were performed endoscopically under intravenous conscious sedation. A restricted balanced diet (approximately 1200 kcal/day) and 150 minutes/week of moderate-intensity exercise were prescribed after balloon placement in a multidisciplinary approach. Outcome measures were collected and assessed in a prospective manner. RESULTS: Median procedure time was 25 (range 19-45) minutes and median hospital stay was 2 (range 1-6) days. Median BW and BMI loss were 15.3 (range 5.3-30.9) kg and 5.6 (range 1.9-12.5) kg/m2 after IGB. The median waist circumference (WC) loss was 9 (range 4-23) cm, and 66.7% of patients were highly satisfied with the treatment. No serious complication related to IGB was observed. CONCLUSION: IGB is a safe and effective device that achieves moderate weight loss in obese ethnic Chinese patients.

The effect of endoscopic therapy in patients receiving omeprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison.

BACKGROUND: The optimal treatment of ulcers with nonbleeding visible vessels and adherent clots is unclear. OBJECTIVE: To compare intravenous omeprazole infusion plus endoscopic therapy with intravenous omeprazole infusion alone for prevention of recurrent bleeding from ulcers with nonbleeding visible vessels or adherent clots. DESIGN: Single-blind randomized study with blinded evaluation of study end points. SETTING: An endoscopy center in a university hospital in Hong Kong. PATIENTS: 156 persons with upper gastrointestinal bleeding and ulcers showing nonbleeding visible vessels or adherent clots. INTERVENTION: Combination of endoscopic therapy and omeprazole infusion versus sham endoscopic therapy and omeprazole infusion. MEASUREMENTS: Recurrent ulcer bleeding before discharge and within 30 days. RESULTS: 78 patients were recruited in each group. Ulcer bleeding recurred before discharge in seven patients who received intravenous omeprazole alone (9%) and no patients who received combined therapy (difference, 9 percentage points [95% CI, 1.7 to 17.6 percentage points]; P = 0.01). The probability of recurrent bleeding within 30 days was 11.6% (9 patients) in the omeprazole-alone group and 1.1% (1 patient) in the combined therapy group (difference, 10.5 percentage points [CI, 1.7 to 19.8 percentage points]; P = 0.009). Patients in the combined therapy group required less transfusion (difference in median units of blood transfused, 1 unit [CI, 0 to 2 units]; P = 0.02). One patient in the combined therapy group had surgery for ulcer perforation. Four patients receiving omeprazole alone (5.1%) and two patients receiving combined therapy (2.6%) died within 30 days. CONCLUSION: The combination of endoscopic therapy and omeprazole infusion is superior to omeprazole infusion alone for preventing recurrent bleeding from ulcers with nonbleeding visible vessels and adherent clots.

Long-term Results on Weight Loss and Diabetes Remission after Laparoscopic Sleeve Gastrectomy for A Morbidly Obese Chinese Population.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective stand-alone bariatric procedure with favorable short-term results on weight reduction and comorbidity resolution. This study aims to evaluate the long-term results of LSG to see if weight reduction and diabetic improvement are sustainable. METHODS: We conducted a prospective observational study on patients receiving LSG as an index stand-alone bariatric operation in our unit. RESULTS: Between 2006 and 2014, there were 140 patients (91 females) aged 37.9 ± 10.5 years with a body mass index of 41.0 ± 7.0 kg/m(2). At 1-year (n = 123), 2-year (n = 99), 3-year (n = 77), 4-year (n = 52), and 5-year (n = 44) follow-ups, the mean percentages of excess weight loss (%EWL) were 70.5, 65.2, 60.2, 53.2, and 57.2%, respectively, while the corresponding proportions with failed weight loss (%EWL <30%) were 7.3, 9.1, 13.0, 25.0, and 22.7%. Weight regain (>25% rebound in %EWL) was evident with time as 0, 1.0, 11.6, 19.2, and 29.5% in the first 5-year follow-ups. In 65 patients with type 2 diabetes mellitus, remission (complete and partial) was achieved in 34.5% at 1-year, 52.7% at 3-year, and 70.6% at 5-year follow-ups. Proportions of patients having optimal glycemic control (HbA1c <7%) increased significantly from 26.2% preoperatively to 80.9% at the first year and maintained at 78.6% at the fifth year (P < 0.001). CONCLUSIONS: LSG was effective in achieving substantial weight reduction and improved diabetic control for morbidly obese patients. Although weight regain was possible with time, majority of patients could maintain sustainable weight loss, diabetes remission, and glycemic improvement in the long run.

Impact on obesity-related illnesses and quality of life following intragastric balloon.

BACKGROUND: The impact of intragastric balloon (IGB) on obesity-related illnesses and quality of life (QOL) has not been previously investigated. METHOD: One hundred and nineteen consecutive obese patients (86 females; mean age 37.8; mean body weight (BW) 103.7 +/- 24.1 kg; mean BMI 38.4 +/- 8.0 kg/m(2)) who underwent IGB were evaluated for improvement on obesity-related illnesses and QOL after weight reduction in a multidisciplinary university referral center. Bioenterics Intragastric balloon (BIB system was employed in the study. RESULTS: Mean treatment period was 169.9 +/- 34.8 days. Mean BW, BMI, and excess body weight loss were 12.4 +/- 6.9 kg, 4.6 +/- 2.7 kg/m(2), and 45.1 +/- 35.3%. Mean waist circumference and biceps fold and triceps fold loss were 10.5 +/- 8.3, 9.8 +/- 8.5, and 8.7 +/- 7.4 cm respectively. Metabolic syndrome was decreased from 42.9% to 15.1% after IGB (p < 0.0005). Improvement of obesity-related illnesses were significant in fasting glucose, cholesterol, triglyceride, C-reactive protein, and blood pressure (p < 0.005).In 28 diabetes patients, HBA1C level was significantly decreased as compared to baseline (7.4 vs. 5.8%; p < 0.0005). The QOL of patients was significantly improved after IGB (p < 0.05). No serious complication related to IGB was observed. Four patients (3.3%) had intolerance and required early removal of balloon. Thirty-one patients (26%) received further bariatric surgery after IGB. CONCLUSIONS: IGB produces meaningful weight loss and significantly improves obesity-related illnesses and quality of life.

Comparison of EUS and ERCP in the investigation with suspected biliary obstruction caused by choledocholithiasis: a randomized study.

BACKGROUND: EUS may be used to reduce the need of diagnostic ERCP. OBJECTIVE: Our purpose was to investigate the benefits and safety of an EUS-guided versus an ERCP-guided approach in the management of suspected biliary obstructive diseases caused by choledocholithiasis, in whom a US study is not diagnostic. DESIGN: A randomized study. SETTING: A university medical unit. PATIENTS: Patients with clinical, biochemical, or radiologic suspicion of biliary obstruction. INTERVENTIONS: In the EUS group, therapeutic ERCP was performed at the same EUS session if a lesion was found. In the ERCP group, therapeutic treatment was carried out at the discretion of the endoscopist. MAIN OUTCOME MEASUREMENTS: The number of ERCPs avoided, procedure-related complications, and recurrent biliary symptoms on follow-up at 1 year. RESULTS: Thirty-three patients were randomized to EUS and 32 to ERCP. Three patients (9.4%) had failed ERCPs, whereas all EUS procedures were successful. Nine (27.3%) patients in the EUS group were found to have biliary lesions that were all treated by ERCP. In the ERCP group, 7 (22%) patients had biliary lesions detected that were treated in the same session. More patients had serious complications (bleeding, acute pancreatitis, and umbilical abscess) in the ERCP group. One patient in each group had recurrent biliary symptoms during follow-up. With EUS used as a triage tool, diagnostic ERCP and its related complications could be spared in 49 (75.4%) patients. CONCLUSIONS: In patients suspected to have biliary obstructive disease, EUS is a safe and accurate test to select patients for therapeutic ERCP.