Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection.

BACKGROUND: Current endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be frequent after thermal therapy, such as radiofrequency ablation. OBJECTIVE: To analyse long-term recurrence of neoplasia and BO after successful widespread endoscopic mucosal resection (EMR). DESIGN: In a retrospective analysis, all patients undergoing widespread EMR of neoplastic BO between 2002 and 2007 at two referral centres were followed for at least 3 years after completion of endotherapy. Recurrence was diagnosed if neoplasia and/or BO were detected following previous successful complete removal, defined as at least two negative endoscopies and biopsies. RESULTS: Ninety patients undergoing widespread EMR were included (mean age 63 years; 82 male), 58% of whom underwent additional thermal ablation for minor residual disease. Complete eradication of neoplasia and Barrett's tissue was achieved in 90% of patients. On further follow-up (mean 64.8 months), recurrence of neoplastic and non-neoplastic BO was found in 6.2% and 39.5%, respectively. Recurring neoplasia (3 adenocarcinomas, 1 low-grade and 1 high-grade dysplasia) were found after a median of 44 months (range 38-85) and could be retreated endoscopically. In a multivariate analysis, Barrett's length was the only factor significantly associated with recurrence (OR 2.73). CONCLUSIONS: Even after seemingly complete endoscopic resection, recurrence of BO is frequent and independent of additional thermal therapy. Due to the possibility of neoplasia recurrence even after long disease-free intervals, follow-up should be extended beyond 5 years.

Long-term results after endoscopic drainage and necrosectomy of symptomatic pancreatic fluid collections.

AIMS: To determine the immediate and long-term results of endoscopic drainage and necrosectomy for symptomatic pancreatic fluid collections. METHODS: The data of 80 patients with symptomatic pancreatic fluid collections (mean diameter: 11.7 cm, range 3-20; pseudocysts: 24/80, abscess: 20/80, infected walled-off necrosis: 36/80) referred for endoscopic management from October 1997 to March 2008 were analyzed retrospectively. RESULTS: Endoscopic drainage techniques included endoscopic ultrasound (EUS)-guided aspiration (2/80), EUS-guided transenteric drainage (70/80) and non-EUS-guided drainage across a spontaneous transenteric fistula (8/80). Endoscopic necrosectomy was carried out in 49/80 (abscesses: 14/20; infected necrosis: 35/36). Procedural complications were bleeding (12/80), perforation (7/80), portal air embolism (1/80) and Ogilvie Syndrome (1/80). Initial technical success was achieved in 78/80 (97.5%) and clinical resolution of the collections was achieved endoscopically in 67/80 (83.8%), with surgery required in 13/80 (perforation: four; endoscopically inaccessible areas: two; inadequate drainage: seven). Within 6 months five patients required surgery due to recurrent fluid collections; over a mean follow up of 31 months, surgery was required in four more patients due to recurrent collections as a consequence of underlying pancreatic duct abnormalities that could not be treated endoscopically. The long-term success of endoscopic treatment was 58/80 (72.5%). CONCLUSIONS: Endoscopic drainage of symptomatic pancreatic fluid collections is safe and effective, with excellent immediate and long-term results. Endoscopic necrosectomy has a risk of serious complications. The underlying pancreatic duct abnormalities must be addressed to prevent recurrence of fluid collections.

Malignant gastroduodenal obstruction: retrospective comparison of endoscopic and surgical palliative therapy.

INTRODUCTION: Endoscopic stenting (ES) is a minimally invasive alternative to surgical gastroenterostomy (GE) for palliation of malignant gastroduodenal obstructions. This consecutive, retrospective analysis compares the clinical outcome of all patients undergoing ES or GE in the same period. METHODS: ES was performed at the Endoscopy Department, University Hospital Mannheim or at the Interdisciplinary Endoscopy Department, University Hospital Hamburg-Eppendorf. GE was performed at the Surgical Department, University Hospital Mannheim. All palliative ES or GE on patients with malignant gastroduodenal obstruction without earlier gastric resections between January 2001 and April 2007 were evaluated. Main outcome measurements were ability of solid food intake (gastric outlet obstruction score), persistence of nausea and vomiting (gut function score), length of hospital stay, morbidity, mortality and re-interventions. RESULTS: A total of 44 ES and 43 GE were performed. Nausea and vomiting--measured by means of the gut function score--persisted in significantly more patients in the GE group than in those who underwent stent placement (p = 0.0102). The gastric outlet obstruction score at discharge from the hospital revealed no significant difference in the ability of solid food intake between the groups. The hospital stay was significantly longer in the GE group (p = 0.0003). There was no significant difference in mortality and the rates of complications and re-interventions. CONCLUSION: In this study, ES is a generally equivalent--and in several points superior--alternative to GE for palliation of malignant gastroduodenal obstruction. ES seems to be the less invasive alternative for symptomatic patients. GE has good results in patients with longer survival and can be practiced within abdominal explorations.

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.

OBJECTIVE: After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. METHODS: A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). RESULTS: CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. CONCLUSIONS: In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients.

BACKGROUND AND AIMS: Endoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia. DESIGN: Retrospective cohort study. SETTING: Four tertiary referral centres. PARTICIPANTS: 169 patients (151 males, age 64 years (IQR 57-71), Barrett's oesophagus 3 cm (IQR 2-5)) with early neoplasia in Barrett's oesophagus < or = 5 cm, without deep submucosal infiltration or lymph node metastases, treated by SRER between January 2000 and September 2006. INTERVENTION: Endoscopic resection every 4-8 weeks, until complete endoscopic and histological eradication of Barrett's oesophagus and neoplasia. RESULTS: According to intention-to-treat analysis complete eradication of all neoplasia and all intestinal metaplasia by the end of the treatment phase was reached in 97.6% (165/169) and 85.2% (144/169) of patients, respectively. One patient had progression of neoplasia during treatment and died of metastasised adenocarcinoma (0.6%). After median follow-up of 32 months (IQR 19-49), complete eradication of neoplasia and intestinal metaplasia was sustained in 95.3% (161/169) and 80.5% (136/169) of patients, respectively. Acute, severe complications occurred in 1.2% of patients, and 49.7% of patients developed symptomatic stenosis. CONCLUSIONS: SRER of Barrett's oesophagus < or = 5 cm containing early neoplasia appears to be an effective treatment modality with a low rate of recurrent lesions during follow-up. The procedure, however, is technically demanding and is associated with oesophageal stenosis in half of the patients.

Mediastinal lymph node staging in potentially resectable non-small cell lung cancer: a prospective comparison of CT and EUS/EUS-FNA.

BACKGROUND: Mediastinal lymph node staging (N-staging) is essential to optimize the treatment in non-small cell lung cancer (NSCLC). Transesophageal endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has recently been introduced as a complementary method. However, in most reports, EUS-FNA has been performed in patients who have demonstrated enlarged lymph nodes (LNs) on CT findings. The yield of EUS/EUS-FNA in patients without enlarged mediastinal LNs by CT has so far only been evaluated in a few reports. AIMS: Our aim was to compare the diagnostic accuracy of CT and EUS with or without EUS-FNA (EUS/EUS-FNA) prospectively, for N-stage in all patients with potentially resectable NSCLC, including patients with and without mediastinal LN enlargement based on CT findings. METHODS: Eighty consecutive patients with potentially resectable NSCLC based on CT findings were enrolled in this prospective comparative study, and underwent EUS/EUS-FNA. RESULTS: Pathological N-stage was established in 78 patients, while in another 2 cases, malignant pleural effusion was proven by EUS-FNA, and we avoided further N-staging. In the 78 patients, the prevalence of malignant mediastinal LNs was 21%. The accuracy of EUS/EUS-FNA (91%) was significantly higher than that of CT (71%). The negative predictive value of EUS/EUS-FNA was 90%. In addition, EUS-FNA identified 2 patients as N3 disease in 56 patients without mediastinal LN involvement on CT. CONCLUSIONS: EUS/EUS-FNA gave more accurate N-staging in patients with possibly resectable NSCLC than CT, and is thus considered to be useful to determine the optimal treatment strategy.

EUS-guided drainage of pancreatic pseudocysts, abscesses and infected necrosis.

Endoscopic ultrasound (EUS)-guided drainage has emerged as the leading treatment modality for symptomatic pancreatic fluid collections. Endoscopic ultrasound-guided endoscopic drainage is less invasive than surgery and avoids local complications related to percutaneous drainage. In addition, unlike non-EUS guided endoscopic drainage, EUS-guided drainage is able to drain non-bulging fluid collections and may reduce the risk of procedure-related bleeding. Excellent treatment success rates exceeding 90% have been reported for pancreatic pseudocysts and abscesses. In the context of infected pancreatic necrosis, adjunctive endoscopic necrosectomy is required for effective treatment. With such an aggressive approach, the treatment success rate may reach 81%-92%. The potential complications of concern for EUS-guided drainage are severe bleeding and perforation. To minimize risk, only fluid collections with a mature wall and within 1 cm of the gastrointestinal lumen should undergo endoscopic drainage. Any coagulopathy, if present, should be corrected. Patients with pseudocysts undergoing drainage should also receive prophylactic antibiotics in order to prevent secondary infection of a sterile collection.

Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease.

Identification of dysplasia in inflammatory bowel disease represents a major challenge for both clinicians and pathologists. Clear diagnosis of dysplasia in inflammatory bowel disease is sometimes not possible with biopsies remaining "indefinite for dysplasia." Recent studies have identified molecular alterations in colitis-associated cancers, including increased protein levels of alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2. In order to analyze the potential diagnostic use of these parameters in biopsies from inflammatory bowel disease, a tissue microarray was manufactured from colons of 54 patients with inflammatory bowel disease composed of 622 samples with normal mucosa, 78 samples with inflammatory activity, 6 samples with low-grade dysplasia, 12 samples with high-grade dysplasia, and 66 samples with carcinoma. In addition, 69 colonoscopic biopsies from 36 patients with inflammatory bowel disease (28 low-grade dysplasia, 8 high-grade dysplasia, and 33 indefinite for dysplasia) were included in this study. Immunohistochemistry for alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2 was performed on both tissue microarray and biopsies. p53 and alpha-methylacyl coenzyme A racemase showed the most discriminating results, being positive in most cancers (77.3% and 80.3%) and dysplasias (94.4% and 94.4%) but only rarely in nonneoplastic epithelium (1.6% and 9.4%; P < .001). Through combining the best discriminators, p53 and alpha-methylacyl coenzyme A racemase, a stronger distinction between neoplastic tissues was possible. Of all neoplastic lesions, 75.8% showed a coexpression of alpha-methylacyl coenzyme A racemase and p53, whereas this was found in only 4 of 700 nonneoplastic samples (0.6%). alpha-methylacyl coenzyme A racemase/p53 coexpression was also found in 10 of 33 indefinite for dysplasia biopsies (30.3 %), suggesting a possible neoplastic transformation in these cases. Progression to dysplasia or carcinoma was observed in 3 of 10 p53/alpha-methylacyl coenzyme A racemase-positive, indefinite-for-dysplasia cases, including 1 of 7 cases without and 2 of 3 cases with p53 mutation. It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease.

A standardized injection technique and regimen ensures success and safety of N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos).

BACKGROUND: N-butyl-2-cyanoacrylate has been successfully used for the treatment of bleeding from gastric fundal varices (FV). However, significant rebleeding rates and serious complications including embolism have been reported. OBJECTIVE: Our purpose was to analyze the safety and efficacy of N-butyl-2-cyanoacrylate for FV bleeding by using a standardized injection technique and regimen. DESIGN: Retrospective. SETTING: Two tertiary referral centers. PATIENTS: A total of 131 patients (91 men/40 women) with FV underwent obliteration with N-butyl-2-cyanoacrylate by a standardized technique and regimen. INTERVENTIONS: (1) Dilution of 0.5 mL of N-butyl-2-cyanoacrylate with 0.8 mL of Lipiodol, (2) limiting the volume of mixture to 1.0 mL per injection to minimize the risk of embolism, (3) repeating intravariceal injections of 1.0 mL each until hemostasis was achieved, (4) obliteration of all tributaries of the FV, (5) repeat endoscopy 4 days after the initial treatment to confirm complete obliteration of all visible varices and repeat N-butyl-2-cyanoacrylate injection if necessary to accomplish complete obliteration. MAIN OUTCOME MEASUREMENTS: Immediate hemostasis rate, early rebleeding rate, bleeding-related mortality rate, procedure-related complications, long-term cumulative rebleeding-free rate, and cumulative survival rate. RESULTS: Initial hemostasis and variceal obliteration were achieved in all patients. The mean number of sessions was 1 (range 1-3). The mean total volume of glue mixture used was 4.0 mL (range 1-13 mL). There was no occurrence of early FV rebleeding, procedure-related complications, or bleeding-related death. The cumulative rebleeding-free rate at 1, 3, and 5 years was 94.5%, 89.3%, and 82.9%, respectively. CONCLUSION: Obliteration of bleeding FV with N-butyl-2-cyanoacrylate is safe and effective with use of a standardized injection technique and regimen.

Detection and endoscopic therapy of early esophageal adenocarcinoma.

PURPOSE OF REVIEW: This review summarizes recent progress on endoscopic diagnosis and treatment of esophageal high-grade intraepithelial neoplasia and early adenocarcinoma and critically analyzes the literature in the context of preexisting scientific data. RECENT FINDINGS: Narrow band imaging and computed virtual chromoendoscopy enhanced visualization of the mucosal morphology. The type of mucosal and capillary patterns seen on narrow band imaging predicted the presence of specialized intestinal metaplasia, high-grade intraepithelial neoplasia and early adenocarcinoma. Endocytoscopy lacked sufficient image quality for clinical use currently. Optical coherence tomography had the potential to diagnose specialized intestinal metaplasia and dysplasia. Photodynamic therapy produced long-term ablation of high-grade intraepithelial neoplasia and reduced cancer risk. Endoscopic radiofrequency ablation of Barrett's mucosa did not cause strictures and buried glandular mucosa. Localized and radical or complete circumferential endoscopic mucosal resections were effective and safe. SUMMARY: Virtual chromoendoscopy detected subtle mucosal lesions and facilitated targeted biopsies. Photodynamic therapy was effective in the long term. Endoscopic radiofrequency ablation appeared promising. Localized and radical or complete circumferential endoscopic mucosa resections were effective therapies.

Intraductal chilled saline perfusion to prevent bile duct injury during percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND AND AIM: Radiofrequency ablation (RFA) is a promising, minimally invasive treatment for hepatocellular carcinoma (HCC). However, thermal injury sometimes occurs in the bile duct, potentially leading to a critical situation. The aim of the present study was to investigate whether bile duct injury is reduced by an intraductal chilled saline perfusion (ICSP) through a nasobiliary tube during RFA for HCC. PATIENTS AND METHODS: The baseline incidence of bile duct injury at Gifu Municipal Hospital was 3.1% (13 patients) in 424 patients with HCC treated by percutaneous RFA. In all patients, the tumor was within 5 mm of the central bile duct on CT images. The incidence of bile duct injury was 46% among the 28 selected patients whose tumor was close to the central bile duct. To prevent complications in such high-risk patients, we placed a nasobiliary tube endoscopically before RFA, and performed ICSP during RFA. Forty consecutive patients with tumors close to the central bile duct were enrolled in this study. RESULTS: Of the 40 enrolled patients, only one had biliary injury, whereas the remaining 39 patients were able to avoid it. The incidence of biliary injury was significantly reduced in the ICSP group (1/40, 2.5%) compared to that in the control group (13/28, 46%) (P < 0.0001). Moreover, the liver function 6 months after RFA was also better preserved in the ICSP group according to Child-Pugh grading, thus resulting in a better clinical outcome. CONCLUSIONS: ICSP through a nasobiliary tube is a potential intervention method to prevent biliary injury by percutaneous RFA.

Biliary stent clogging solved by nanotechnology? In vitro study of inorganic-organic sol-gel coatings for teflon stents.

BACKGROUND & AIMS: The major drawback of plastic stents for biliary drainage is the occlusion by sludge. Sludge is accrued because the stent surface allows for the adherence of proteins, glycoproteins, or bacteria and the bile flow is insufficient to clean the surface. In this study, experience from nanotechnology to achieve a clean surface by improved soil-release characteristics is used to optimize biliary stent surface. The aim of this study was to examine sludge accumulation in relation to surface characteristics designed by nanotechnology. METHODS: A variety of inorganic-organic sol-gel-coated stents were incubated in sterilized human bile and enzyme-active Escherichia coli for 35 days. Materials were Teflon (DuPont, Wilmington, DE) coated with hydrophobic Clearcoat (NTC, Tholey, Germany), Teflon with sol-gel coating synthesized of organic epoxides of 190 g/mol or 500 g/mol, and propylaminosilane without or with fluorsilanes for increased hydrophobicity. Scanning electron microscopy and semiquantitative analysis, blinded to the type of coating, were used to determine the amount of sludge accumulated on the surface. RESULTS: Sludge deposition was reduced on the designed surfaces as compared with uncoated Teflon and Clearcoat. The performance of high molecular (500 g/mol) was superior to that of low molecular (190 g/mol) epoxide ligand. However, increasing hydrophobicity by adding fluoraminosilanes resulted in increased adherence of sludge. Less than a micrometer-thin sol-gel coating is inexpensive because very little coating material is required. This is the first published data comparing systematically modified surfaces of biliary stents using nanotechnology. CONCLUSIONS: Optimized soil release by sol-gel nanocoating of plastic stents may prevent biliary plastic stents from clogging.

One-step, simultaneous double-wire technique facilitates pancreatic pseudocyst and abscess drainage (with videos).

BACKGROUND: EUS-guided pancreatic pseudocyst and abscess drainage ideally requires the insertion of both a transmural stent and nasocystic catheter to ensure continuous irrigation and effective drainage. Sequential stent and nasocystic catheter insertion may be time consuming because of the difficulty in recannulating the pseudocyst after the initial stent placement. OBJECTIVE: Our purpose was to describe a novel one-step simultaneous double-wire technique that facilitates effective pancreatic pseudocyst and abscess drainage. DESIGN: To solve the problem of recannulating the pseudocyst cavity after the initial transmural stent placement, we developed a prototype 3-layer puncture kit that allows the simultaneous insertion of 2 guidewires at the initial puncture in one step. This puncture kit consists of a 22-gauge needle used for FNA, a 6F inner polytetrafluoroethylene (Teflon) catheter, and an outer 8.5F Teflon catheter. SETTING: Tertiary referral center. PATIENTS: Eight consecutive patients were treated. INTERVENTIONS: With use of a therapeutic linear echoendoscope and the assembled kit with the needle protruding out distally, the pseudocyst cavity was punctured by using electrocautery. The needle and the inner catheter were then withdrawn, leaving the outer catheter within the cavity. The size of this outer catheter permitted the simultaneous insertion of two 0.035-inch guidewires. Sequential insertion of a transmural stent and nasocystic catheter was then performed without a need for recannulation of the pseudocyst or abscess cavity. MAIN OUTCOME MEASUREMENTS: Successful endoscopic drainage. RESULTS: All patients were successfully treated without complications. Mean procedural time was 32.5 minutes (range 25-45 minutes). CONCLUSIONS: With this novel technique, establishing an irrigation system for the treatment of pancreatic pseudocysts and abscesses becomes easier, faster, and safer.

Use of modified multiband ligator facilitates circumferential EMR in Barrett's esophagus (with video).

BACKGROUND: Various techniques are available for EMR in the upper- and lower-GI tract. For early cancers of the esophagus, the "suck and cut" technique, which uses a transparent cap or variceal band ligator, is the most commonly practiced method. To facilitate multiple or circumferential EMR, a modified multiband variceal ligator (MBL) is introduced, which allows sequential banding and snare resection without the need to withdraw the endoscope. OBJECTIVE: To study the feasibility of modified MBL device in facilitating circumferential EMR of Barrett's esophagus (BE) that contains high-grade intraepithelial neoplasia (HGIN) and/or intramucosal cancer (IMC). DESIGN: To enable band delivery with a snare inserted in the therapeutic endoscope, the threading channel of the cranking device is enlarged from 2 to 3.2 mm. The 6-shooter MBL was used. PATIENTS: Ten consecutive patients (all men; median age, 62 years; range 43-82 years) with BE were treated. IMC and HGIN were found in 8 and 2 patients, respectively. INTERVENTIONS: EMR was performed with pure coagulating current when using a 1.5 x 2.5-cm mini hexagonal polypectomy snare. No submucosal saline solution injection was performed before resection. RESULTS: In 5 of 10 patients with circumferential BE of 2 to 9 cm in length (median, 4 cm), complete circumferential EMR was performed in 1 session by using 3 to 18 bands (median, 6). Four patients with 3- to 10-cm (median, 4 cm) long segment BE required 2 to 5 sessions (median, 3) with a total of 5 to 42 bands (median, 12). Another patient with multifocal HGIN and/or IMC in 24 of a total of 49 specimens was finally recommended for surgery because of technical difficulties caused by mural thickening after 4 sessions. No serious procedure-related complications were observed, except for 2 minor bleedings, which were controlled endoscopically. Seven patients developed strictures after circumferential EMR. All patients except 1 were successfully managed by weekly bougienage after a median of 5 sessions (range 3-11). Deep-wall tears developed in 1 patient during the fourth bougienage session, for which limited distal esophageal resection was performed with an uneventful outcome. CONCLUSIONS: The novel technique of MBL-EMR described here facilitated and simplified circumferential removal of BE that contained HGIN and/or IMC. However, the method is associated with a very high stricture rate if circumferential EMR is performed in a single session. Complete removal of BE should be achieved by repeated partial EMR. Long-term follow-up is needed to observe for late recurrence and to determine the clinical impact of this method.