Justin C. Wu

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. METHODS We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. RESULTS We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). CONCLUSIONS After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.

Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen

BACKGROUND Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients. METHODS We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months. RESULTS We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005). CONCLUSIONS Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.

Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding: A Randomized Trial

BACKGROUND It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin. OBJECTIVE To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases. DESIGN A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725) SETTING A tertiary endoscopy center. PATIENTS Low-dose aspirin recipients with peptic ulcer bleeding. INTERVENTION 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up. MEASUREMENTS The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks. RESULTS 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, -3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]). LIMITATIONS The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy. CONCLUSION Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.

Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial.

BACKGROUND Whether Helicobacter pylori increases the risk of ulcers in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) is controversial. We hypothesised that eradication of H pylori infection would reduce the risk of ulcers for patients starting long-term NSAID treatment. METHODS Patients were enrolled if they were NSAID naïve, had a positive urea breath test, had dyspepsia or an ulcer history, and required long-term NSAID treatment. They were randomly assigned omeprazole triple therapy (eradication group) or omeprazole with placebo antibiotics (placebo group) for 1 week. All patients were given diclofenac slow release 100 mg daily for 6 months from randomisation. Endoscopy was done at 6 months or if severe dyspepsia or gastrointestinal bleeding occurred. The primary endpoint was the probability of ulcers within 6 months. Analyses were by intention to treat. FINDINGS Of 210 arthritis patients screened, 128 (61%) were positive for H pylori. 102 patients were enrolled, and 100 were included in the intention-to-treat analysis. H pylori was eradicated in 90% of the eradication group and 6% of the placebo group. Five of 51 eradication-group patients and 15 of 49 placebo-group patients had ulcers. The 6-month probability of ulcers was 12.1% (95% CI 3.1-21.1) in the eradication group and 34.4% (21.1-47.7) in the placebo group (p=0.0085). The corresponding 6-month probabilities of complicated ulcers were 4.2% (1.3-9.7) and 27.1% (14.7-39.5; p=0.0026). INTERPRETATION Screening and treatment for H pylori infection significantly reduces the risk of ulcers for patients starting long-term NSAID treatment.

Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis

Background: Hemoclips, injection therapy and thermocoagulation (heater probe or electrocoagulation) are the most commonly used types of endoscopic hemostasis for the control of non-variceal gastrointestinal bleeding. Aim: To compare the efficacy of hemoclips versus injection or thermocoagulation in endoscopic hemostasis by pooling data from the literature. Method: Publications in the English literature (MEDLINE, EMBASE and Cochrane Library) as well as abstracts in major international conferences were searched using the keywords “hemoclips” and “bleeding”, and 15 trials fulfilling the search criteria were found. Outcome measures included: initial hemostasis (after endoscopic intervention); recurrent bleeding; definitive hemostasis (no recurrent bleeding until the end of follow-up); the requirement for surgical intervention; and all-cause mortality. The heterogeneity of trials was examined and the effects were pooled by meta-analysis. Results: Of 1156 patients recruited in the 15 studies, 390 were randomly assigned to receive clips alone, 242 received clips combined with injection, 359 received injection alone, and 165 received thermocoagulation with or without injection. Definitive hemostasis was higher with hemoclips (86.5%) than injection (75.4%; RR 1.14, 95% CI 1.00–1.30), or endoscopic clips with injection (88.5%) compared with injections alone (78.1%; RR 1.13, 95% CI 1.03–1.23), leading to a reduced requirement for surgery but no difference in mortality. Compared with thermocoagulation, there was no improvement in definitive hemostasis with clips (81.5% versus 81.2%; RR 1.00, 95% CI 0.77–1.31). These estimates were robust in sensitivity analyses. There was also no difference between clips and thermocoagulation in rebleeding, the need for surgery and mortality. The reported locations of failed hemoclip applications included posterior wall of duodenal bulb, posterior wall of gastric body and lesser curve of the stomach. Conclusion: Successful application of hemoclips is superior to injection alone but comparable to thermocoagulation in producing definitive hemostasis. There was no difference in all-cause mortality irrespective of the modalities of endoscopic treatment.

The Effect of Endoscopic Therapy in Patients Receiving Omeprazole for Bleeding Ulcers with Nonbleeding Visible Vessels or Adherent Clots: A Randomized Comparison

Context Endoscopic hemostasis plus omeprazole in patients with actively bleeding ulcers prevents recurrent bleeding. Are both needed if endoscopy shows a nonbleeding vessel or nonbleeding clot? Contribution This randomized trial included 156 patients admitted for bleeding whose endoscopies, performed within 24 hours of admission, showed ulcers with nonbleeding vessels or adherent clots. Approximately 12% of patients receiving omeprazole alone had recurrent bleeding within 30 days compared with approximately 1% who received endoscopic hemostasis (thermocoagulation and epinephrine injection) plus omeprazole. Implications Endoscopic hemostasis plus omeprazole better prevents recurrent bleeding than does omeprazole alone in patients who have recently bled from an ulcer but do not have actively bleeding vessels at endoscopy. The Editors Endoscopic hemostasis is effective in controlling bleeding from peptic ulcers. The optimal treatment of ulcers with nonbleeding visible vessels and adherent clots, however, is unclear. The controversy arises from variability in endoscopic diagnosis as well as in the standard treatment strategies adopted by endoscopists for ulcers with adherent clots. At least two studies have shown that even experienced endoscopists have different definitions of stigmata at the ulcer base (1, 2). Among the stigmata of hemorrhage, clot and protuberant vessels are the most difficult to differentiate. After a clot has been diagnosed, approaches to management are quite different. Some clinicians flush the clot with a syringe or oral irrigator, which in general produces rather weak irrigate (3), whereas others advocate targeted irrigation using thermal probes (4). With these methods of irrigation, the success rates for exposing the underlying stigmata range from 9% (3) to 57% (4). Even after removal of blood clots, it is not certain whether endoscopic therapy prevents recurrent bleeding or actually provokes it. Randomized, controlled trials of endoscopic therapy versus no endoscopic therapy have yielded conflicting results (5, 6), and meta-analysis does not support routine use of endoscopic therapy (7). The advent of proton-pump inhibitors changed the standard of practice in the management of bleeding ulcers. Two studies from India have demonstrated the benefit of high-dose oral omeprazole for peptic ulcer bleeding. Khuroo and colleagues (8) demonstrated that a 5-day course of oral omeprazole, 40 mg twice daily, reduced recurrent bleeding even without endoscopic therapy. The benefit of omeprazole was most remarkable among patients with visible vessels or adherent clots at the ulcer bases. Javid and associates (9) showed that the same omeprazole regimen in combination with endoscopic injection prevented recurrent bleeding. Their study, however, failed to demonstrate a distinct advantage of omeprazole in patients with nonbleeding visible vessels and adherent clots. A recent randomized study by Jensen and coworkers (10) compared twice-daily administration of an oral proton-pump inhibitor with endoscopic therapy in 32 patients who were at high risk for ulcer hemorrhage. Six of 17 medically treated patients had recurrent bleeding compared with none of 15 patients treated endoscopically. The study was discontinued prematurely because of the dramatic difference in clinical outcome. Study limitations included small sample size, unequal distribution of confounding factors, and lack of difference in clinical end points (11). The effectiveness of proton-pump inhibitors alone for ulcers that are not actively bleeding but have stigmata of a nonbleeding visible vessel or an adherent clot remains undetermined. We previously demonstrated that high-dose intravenous omeprazole as an adjunct to endoscopic therapy substantially reduced risk for recurrent bleeding, repeated endoscopy, frequency of blood transfusion, and duration of hospitalization (12). Subgroup analysis suggested that actively bleeding ulcers, as well as ulcers with a nonbleeding visible vessel or an adherent clot, benefited from the treatment. In the current study, we compared high-dose intravenous omeprazole infusion plus endoscopic therapy with intravenous omeprazole infusion alone for prevention of recurrent bleeding from ulcers with a nonbleeding visible vessel or an adherent clot. Methods Description of the Study and Patients We performed a single-center randomized trial comparing the combination of endoscopic therapy and high-dose omeprazole infusion with high-dose omeprazole infusion alone for treatment of ulcers with a nonbleeding visible vessel or an adherent clot. This study was conducted at the Endoscopy Center of the Prince of Wales Hospital in Hong Kong. The clinical trials ethics committee of the faculty of medicine of the Chinese University of Hong Kong approved the study protocol. Consecutive patients who presented with signs of upper gastrointestinal bleeding underwent endoscopic examination within 24 hours of hospital admission. Patients who were in shock or were vomiting fresh blood at presentation underwent urgent endoscopy as soon as their hemodynamic conditions stabilized. All endoscopic examinations were performed by using a dual-channel endoscope (Olympus 2T200, Olympus Japan Co., Tokyo, Japan). All participants provided written informed consent before the endoscopic examinations. At endoscopy, gastric or duodenal ulcers were examined to determine whether they were actively bleeding (spurting or oozing) or showed nonbleeding visible vessels or adherent clots. A nonbleeding visible vessel was defined as a protuberant discoloration according to the National Institutes of Health 1989 consensus statement (13). Ulcers with overlying clots were irrigated for 5 minutes with a 3.2-mm heater probe (Olympus CD-10Z, Olympus Japan Co.) to remove loosely attached clots and debris. An adherent clot was defined as a blood clot that remained attached to the ulcer base after the 5-minute period of irrigation (3). Patients met the inclusion criteria if they were at least 16 years of age and had benign gastroduodenal ulcers showing nonbleeding visible vessels or adherent clots at endoscopy. Patients were excluded if they 1) had actively bleeding ulcers, including ulcers in which endoscopic irrigation procedures provoked bleeding before treatment; 2) had had endoscopic therapy for bleeding ulcer within the past 30 days; 3) had a history of gastric surgery; 4) were pregnant; 5) had malignant ulcers; or 6) did not provide written informed consent. Specimens were taken from the antrum for urease biopsy and histologic examination to determine Helicobacter pylori status. Patients found to have malignant ulcers after initial enrollment were excluded from the analysis. Randomization and Treatment Protocol Randomization was performed when ulcers were judged to show a nonbleeding visible vessel or an adherent clot after 5 minutes of irrigation. Patients were randomly assigned to receive endoscopic therapy or sham endoscopic treatment. Randomization was carried out through the use of a computer-generated list of random numbers in blocks of 10. Allocation concealment was performed by an independent research nurse who assigned treatments according to consecutive numbers in sealed opaque envelopes. Patients randomly assigned to endoscopic therapy were treated with epinephrine injection followed by thermocoagulation. Diluted epinephrine (1:10 000 dilution) was injected in 0.5-mL or 1-mL aliquots around the nonbleeding visible vessels or adherent clots to induce tissue blanching and edema. In general, approximately 5 mL of diluted epinephrine was injected. The vessels were then thermocoagulated by using a 3.2-mm heater probe (30 J for 6 seconds). The end point of endoscopic treatment was defined by the flattening or cavitation of protuberances. Adherent clots were removed by cheese-wiring using a mini-snare, and the ulcer base was again examined. Underlying vessels were coagulated in a similar fashion. In the event of provoked bleeding, cessation of bleeding and flattening or cavitation of protuberances constituted successful treatment. Patients randomly assigned to sham endoscopic treatment underwent gentle irrigation of the ulcer base using a syringe but no manipulation with the heater probe, mini-snare, or suction. Any bleeding provoked after randomization was included in the intention-to-treat analysis. All patients received intravenous omeprazole (Losec, AstraZeneca, Molndal, Sweden) after randomization. A bolus injection of omeprazole, 80 mg, was given during the endoscopic procedure and was followed immediately by a continuous infusion of 8 mg/h for 72 hours. Follow-up After the endoscopic procedure, an independent team of physicians who were blinded to treatment assignments monitored the patients in a gastroenterology ward for signs of recurrent bleeding. The endoscopists were not involved in subsequent patient management. A research nurse kept endoscopy records in opaque sealed envelopes that were not accessible to physicians, investigators, or patients. Blood pressure and pulse rate were monitored hourly during the first 24 hours and every 4 hours thereafter until discharge. After finishing 72 hours of omeprazole infusion, patients were prescribed 20 mg of oral omeprazole per day. Those who had no evidence of recurrent bleeding were discharged within 5 days of hospitalization. Patients who had positive results on urease biopsy also received a 1-week course of omeprazole (20 mg twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1 g twice daily). All patients were evaluated for evidence of delayed recurrent bleeding at day 30. End Points The primary end points were recurrent ulcer bleeding before discharge and within 30 days, according to prespecified criteria. Bleeding was considered to have recurred if any of the following were documented: vomiting of fresh blood; shock (defined as a systolic blood pressure < 90 mm Hg or pulse rate > 110 b

Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding

BACKGROUND AND STUDY AIMS Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated. PATIENTS AND METHODS In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed. RESULTS 20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up. CONCLUSION These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.

Genetics of inflammatory bowel disease in Asia: Systematic review and meta-analysis

Background: Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease‐predisposing genes in Asian IBD patients. Methods: A systematic review and meta‐analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews. Results: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age‐ and sex‐matched controls. Major nucleotide oligomerization domain (NOD)‐2 variants in Western Crohns disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy‐related protein 16‐linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84–1.13). Interleukin (IL)‐23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16–2.82) and a single nucleotide polymorphism in IL‐23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15–0.60). Tumor necrosis factor (TNF) superfamily gene‐15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86–3.86), while TNF‐308 polymorphisms (OR 1.82; 95% CI 1.15–2.9), cytotoxic T lymphocyte antigen (CTLA)‐4 (OR 2.75; 95% CI 1.22–6.22) and MICA allele (OR 2.41; 95% CI 1.89–3.07) were associated with ulcerative colitis in Asians. Conclusions: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease‐associated mechanisms in this population of rising incidence. (Inflamm Bowel Dis 2012;)

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

Objective The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. Design 442 incident cases (186 Crohns disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. Results In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. Conclusions This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

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.