J.Steven Burdick

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

BACKGROUND Endoscopic ablation to treat Barretts 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 Barretts 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.

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.

Chronic subcutaneous Octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome

Background A patient affected by blue rubber–bleb nevus syndrome had chronic gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple surgical and endoscopic procedures to treat the venous malformations, the patient continued to bleed primarily from lesions in the small bowel. Therefore, this patient was treated with octreotide, a somatostatin analog known to decrease splanchnic blood flow and that is used for acute and chronic gastrointestinal bleeding. Methods Octreotide therapy, 5.7 &mgr;g/kg subcutaneously twice daily, was initiated, and the patient was followed up clinically. Complete blood counts, blood glucose concentration, pancreatic enzyme concentration, liver function tests, and growth hormone concentration were monitored during treatments. Results During the 4 weeks after initiation of octreotide therapy, hemoglobin concentration was maintained without the need for transfusions. Octreotide decreased the patients monthly need for blood transfusion from 52 ± 7 mL · kg−1 · mo−1 of packed red blood cells to 23 ± 7 mL · kg−1 · mo−1. She had no detectable side effects or growth inhibition. Other medical interventions including -εaminocaproic acid, nadolol, and total parenteral nutrition with bowel rest were not as effective as octreotide alone. Conclusion Octreotide decreased the patients need for blood transfusions. Possible mechanisms include altering blood flow to the gastrointestinal tract and direct effects on the venous malformations.

In situ hybridization for telomerase RNA in routine cytologic brushings for the diagnosis of pancreaticobiliary malignancies

BACKGROUND Brush cytology for the diagnosis of pancreaticobiliary malignancy has an overall sensitivity of 50%. Accurate and specific markers are therefore needed for the optimal evaluation of pancreaticobiliary strictures. Telomerase activity is present in 85% to 90% of all human cancers. We sought to determine the utility of in situ hybridization for telomerase RNA in endoscopic brushings for the diagnosis of pancreaticobiliary malignancy. METHODS Endoscopic brushings from 18 patients with pancreatic or biliary strictures were evaluated by routine cytology and in situ hybridization for telomerase RNA. RESULTS Eight of 18 strictures were malignant. Cytology was positive in 5 patients, whereas telomerase RNA was positive in 6. All malignancies were diagnosed by either cytology or telomerase RNA; however, both studies were positive in only 3. There were no false-positive results by either technique. CONCLUSION The detection of telomerase RNA in endoscopic brushings may be an important adjunct to cytology for cancer diagnosis in pancreaticobiliary strictures.

Gastric leiomyosarcoma presenting as a gastric wall abscess

Gastric abscess is a rare disorder with approximately 500 cases reported. Two variants are seen diffuse (Phlegemous) or localized. We report a spindle cell tumor (leiomyosarcoma) presenting as a localized gastric wall abscess.

Chronic Treatment of Ménétrier’s Disease With Erbitux: Clinical Efficacy and Insight Into Pathophysiology

BACKGROUND & AIMS Ménétriers 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 Ménétriers disease and also provides insight into the pathophysiology of the protein-losing gastropathy.

Holmium laser for treatment of left hepatic duct stone

Endoscopic biliary lithotripsy can generally be performed using mechanical techniques. However, this has a failure rate of 10% to 15% even if performed by experienced endoscopists.1 Failure occurs when stones cannot be captured in a basket or when sufficient mechanical pressure cannot be applied to achieve fragmentation. Nonsurgical options are available for treatment of these refractory stones including extracorporeal or intracorporeal lithotripsy. Intracorporeal lithotripsy can be performed with various modalities including electrohydraulic devices or pulse dye lasers, including alexandrite, coumarin, or rhodamine lasers.2-4 A new laser (holmium:yttrium aluminum garnet [Ho:YAG]) has been developed for lithotripsy, although it also has soft tissue applications.5,6 The mechanism of lithotripsy with the holmium laser differs from that of pulse dye lasers. We report the use of a holmium laser to successfully remove a refractory left hepatic duct stone that could not be removed by percutaneous and endoscopic basket methods.

Acalculous cholecystitis presenting as hemobilia and jaundice

The term hemobilia was first used by Sandblom to describe bleeding into the biliary system after a subcapsular liver injury.1 The term is now used to describe bleeding into the biliary system from any cause. The diagnosis and evaluation of hemobilia may be facilitated by the widespread availability of new imaging techniques.2 The most frequent causes are trauma, infections, tumors, inflammatory disorders, and gallstones.2-7 In a review of published reports Bismuth summarized 355 well-documented cases of hemobilia.8 Of these, 53% originated in the liver, 23% in the gallbladder, 22% in the bile ducts, and 2% in the pancreas. Of those cases in which hemobilia originated in the gallbladder, almost all were related to gallstones. Among the 30 reported cases of hemorrhagic cholecystitis, there is only one case of hemobilia due to acalculous cholecystitis.9 Cappell et al.6 reported a second case of hemobilia associated with acalculous cholecystitis, but the bleeding was thought to have been from a benign gallbladder polyp.6 We report two patients with hemobilia due to acalculous cholecystitis.