Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE: To assess the safety and efficacy of CRYO in BE with HGD. DESIGN: Multicenter, retrospective cohort study. SETTING: Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS: CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS: CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

BACKGROUND: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN: Multicenter, retrospective cohort study. SETTING: Ten academic and community medical centers between 2006 and 2009. PATIENTS: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS: Complete eradication of luminal cancer and adverse events. RESULTS: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS: Retrospective study design, short follow-up. CONCLUSIONS: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS: Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasm (IPMN) is characterized by enhanced mucus secretion. It is a benign or low-grade neoplasm associated with a dilated main pancreatic duct, patulous ampullary orifice, and abundant mucus secretion. Foci of aggressive cancer may arise and become invasive. Surgery is the only treatment that can cure IPMN, but the extent of pancreatic resection and the intraoperative margins remain areas of controversy. The risks of total pancreatectomy must be weighed against the risk for developing cancer in the residual pancreas. Risks must be factored against the natural course of the disease and the likelihood of malignancy developing over the life expectancy.

Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia.

BACKGROUND: Barrett's esophagus (BE) with high-grade dysplasia (HGD) is a risk factor for development of esophageal carcinoma. Photodynamic therapy (PDT) with Photofrin (PHO) has been used to eliminate HGD in BE. OBJECTIVE: Our purpose was to compare PHOPDT plus omeprazole with omeprazole only (OM). DESIGN: Five-year follow-up of a randomized, multicenter, multinational, pathology-blinded HGD trial. SETTING: 30 sites in 4 countries. PATIENTS: 208. INTERVENTIONS: Patients with BE and HGD were randomized (2:1) to PHOPDT (n=138) or OM (n=70) into a 2-year trial followed up for 3 more years. PHOPDT patients received 2 mg/kg PHO intravenously followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40 to 50 hours to a maximum of 3 courses at least 90 days apart. Both groups received 20 mg of OM twice daily. Pathologists at one center assessed biopsy specimens in a blinded fashion. MAIN OUTCOME MEASUREMENT: HGD ablation status over 5 years of follow-up. RESULTS: At 5 years PHOPDT was significantly more effective than OM in eliminating HGD (77% [106/138] vs 39% [27/70], P<.0001). A secondary outcome measure preventing progression to cancer showed a significant difference (P=.027) with about half the likelihood of cancer occurring in PHOPDT (21/138 [15%]) compared with OM (20/70 [29%]), with a significantly (P=.004) longer time to progression to cancer favoring PHOPDT. LIMITATIONS: Not all patients were available for follow-up. CONCLUSIONS: This 5-year randomized trial of BE patients with HGD demonstrates that PHOPDT is a clinically and statistically effective therapy in producing long-term ablation of HGD and reducing the potential impact of cancer compared with OM.

Management of pancreas divisum.

Pancreas divisum is the most common congenital anomaly of the pancreas. Abnormal hedgehog protein signaling appears related to the formation of several pancreatic malformations, including annular pancreas, pancreatic-biliary malunion, pancreatic rests, and pancreas divisum. Pancreas divisum by itself should not necessarily require intervention. A careful evaluation should be performed to exclude other causes of symptoms. If the patient is asymptomatic, no further evaluation is necessary. However, a significant percentage of patients with pancreas divisum and acute recurrent pancreatitis benefit from intervention. Surgical sphincteroplasty and endoscopic interventions appear similar in outcome. Thus, endoscopic intervention with prophylactic temporary stenting is advised as initial therapy. Surgery should be reserved for patients with chronic pancreatitis.

Multicenter, randomized, controlled trial of virtual-reality simulator training in acquisition of competency in colonoscopy.

BACKGROUND: The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience. OBJECTIVE: To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy. DESIGN: Randomized, controlled, blinded, multicenter trial. SETTING: Academic medical centers with accredited gastroenterology training programs. PATIENTS: First-year GI fellows. INTERVENTIONS: Subjects were randomized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship. After this period, both groups began performing real colonoscopies. The first 200 colonoscopies performed by each fellow were graded by proctors to measure technical and cognitive success, and patient comfort level during the procedure. MAIN OUTCOME MEASUREMENTS: A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time. RESULTS: Forty-five fellows were randomized from 16 hospitals over 2 years. Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases. A mixed-effects model demonstrated a higher objective competence overall in the simulator group (P < .0001), with the difference between groups being significantly greater during the first 80 cases performed. The median number of cases needed to reach 90% competency was 160 in both groups. The patient comfort level was similar. CONCLUSIONS: Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training.

Chronic treatment of Ménétrier's disease with Erbitux: clinical efficacy and insight into pathophysiology.

BACKGROUND & AIMS: Ménétrier's disease is a rare premalignant hypertrophic gastropathy characterized by large rugal folds, foveolar hyperplasia with glandular atrophy, hypochlorhydria, and hypoalbuminemia. Patients with severe disease often exhibit refractory nausea and vomiting and require gastrectomy. Evidence from both mice and human beings suggests a critical role for epidermal growth factor receptor (EGFR) signaling in the pathogenesis of this disease. We previously reported significant clinical and biochemical improvement of a single patient treated for 1 month with Erbitux, a monoclonal antibody that blocks ligand binding to EGFR. METHODS/RESULTS: We describe 2 patients who were given longer-term treatment with Erbitux as an alternative to gastrectomy. The first patient presented with nausea, hypoalbuminemia, and peripheral edema that required total parenteral nutrition (TPN) and infusions of albumin. On institution of Erbitux, there was rapid improvement in nausea and vomiting and stabilization of serum albumin with discontinuation of TPN and albumin infusions. Serum albumin remained stable during a 1-year course of Erbitux without supplemental protein. Application before and after Erbitux of the radiopaque dye ruthenium red to biopsies of the gastric oxyntic gland mucosa demonstrated prompt and persistent closure of tight junctions by electron microscopy. The second patient presented with chronic gastric bleeding that required bimonthly blood transfusions. During a 4-month course of Erbitux, his hematocrit stabilized, and transfusion requirements were eliminated. CONCLUSIONS: The present report demonstrates the efficacy of prolonged Erbitux therapy in patients with different presentations of severe Ménétrier's disease and also provides insight into the pathophysiology of the protein-losing gastropathy.

Endoscope reprocessing and repair costs.

Endoscope reprocessing and repair are important factors in regard to patient safety, optimal endoscope function, and costs. Endoscope reprocessing requires high level disinfection. There are three steps in reprocessing; mechanical cleaning, disinfection, and that is followed by rinsing and drying. The most critical step is mechanical cleaning which results in a 10 (4) reduction in microbial contamination or bioburden. Improper cleaning can overwhelm high-level disinfection regardless of subsequent steps and is the most susceptible to error. Endoscopy costs are dependent on costs of instruments, cleaning costs, and repair costs. The average repair costs at our endoscopy unit remained stable for more than 4 years suggesting a durable life of use. Consideration of endoscope accessories use should consider potential damage to endoscope use, cost to process re-useable items, sterility, and consideration of recent legislation on reprocessing of single-use devices.

Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia.

CONTEXT: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. OBJECTIVE: To assess the accuracy of CTC in a large number of participants across multiple centers. DESIGN, SETTING, AND PARTICIPANTS: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. MAIN OUTCOME MEASURES: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. RESULTS: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. CONCLUSIONS: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Management of iatrogenic perforation.

Iatrogenic perforation of the gastrointestinal tract is a medical emergency and is inevitable. An endoscopist must maintain a high index of suspicion despite minimal or atypical symptoms and negative radiologic studies, because perforation is a complication with tremendous morbidity and mortality. The endoscopist must know how to manage this complication appropriately and to seek immediate surgical consultation. There is ongoing controversy about when a patient should undergo nonoperative or surgical therapy. An evidence-based approach to manage iatrogenic perforation is not possible. The trend in the modern era is to less invasive, nonoperative therapy, given advancements in ICU care and antibiotics. Laparoscopy or laparoscopic-assisted (minilaparotomy) surgery is also being increasingly used with outcomes comparable with conventional laparotomy. Experience and advancements in accessories have enabled endoscopic repair of iatrogenic perforation in many situations [84]. The management algorithms provided synthesize the pertinent literature into reasonable guidelines to follow. Ultimately, an individualized approach must be taken to manage the patient with an iatrogenic perforation.

Intramural incision technique.

BACKGROUND: Therapeutic ERCP is technically complex. A variety of techniques can be used to achieve biliary access when direct cannulation is difficult. Pre-cut papillotomy can provide immediate access, but this technique is associated with an increased risk of complications. METHODS: An intramural incision technique is described that uses the false tract created with a guidewire to place a papillotome though the intramural portion of the papilla and unroof the biliary orifice. OBSERVATIONS: Biliary access was achieved in 6 consecutive patients in whom access could not be obtained with either a papillotome or guidewire. No major complication occurred. CONCLUSIONS: By virtue of the incision depth, the intramural incision technique offers a safer approach to biliary access than conventional pre-cut techniques. The technique is simple and will be useful when there is aberrant passage of a guidewire.