Kenneth K. Wang

Impact of endoscopist withdrawal speed on polyp yield: Implications for optimal colonoscopy withdrawal time

In 2002, a U.S. Multi‐Society Task Force on Colorectal Cancer recommended that the withdrawal phase for colonoscopy should average at least 6–10u2003min. This was based on 10 consecutive colonoscopies by two endoscopists with different adenoma miss rates.

Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett's esophagus.

BACKGROUND & AIMSnAlthough esophagectomy is the standard of care for treating early adenocarcinoma in Barretts esophagus, the procedure is associated with significant morbidity and mortality. For these patients, the multimodal approach of endoscopic mucosal resection and photodynamic therapy (EMR/PDT) may be a viable, less invasive option.nnnMETHODSnA retrospective review (1996-2001) of all patients undergoing either combined EMR/PDT group or esophagectomy (SURG) for early-stage Barretts adenocarcinoma was performed. Data were collected on patient demographics, tumor staging, procedure-related morbidity and mortality, persistence or recurrence of cancer, and cancer-related deaths after therapy. Differences in outcomes between the 2 groups were assessed.nnnRESULTSnTwenty-four patients were identified in the EMR/PDT group and 64 in the SURG group. The SURG group was found to have a significantly higher procedure-related complication rate compared with the EMR/PDT group (31 vs. 4; P < 0.01). There were no procedure-related deaths in the EMR/PDT group, whereas one death occurred in the SURG group as a result of complications. Eighty-three percent of patients (20 of 24) in the EMR/PDT group and all patients in the SURG group remained free of cancer over a follow-up of 12 +/- 2 and 19 +/- 3 months, respectively. Four patients in the EMR/PDT group failed to respond to therapy; 2 of them underwent alternate therapies and are free of disease, whereas the other 2 died of unrelated causes.nnnCONCLUSIONSnThe combination of EMR/PDT seems to be a viable and less morbid alternative to standard esophagectomy in patients presenting with early Barretts esophageal adenocarcinoma. A prospective randomized, controlled trial of EMR/PDT compared with esophagectomy for managing early adenocarcinoma in Barretts esophagus may be warranted.

Photodynamic therapy in Barrett's esophagus☆

Photodynamic therapy (PDT) was one of the earliest ablative techniques applied to Barretts esophagus. The rationale for this use was the ability to treat large amounts of esophageal mucosa in a single rapid application. Additionally, PDT has the ability to treat early carcinoma and dysplastic tissue. Because a small carcinoma in dysplastic Barretts esophagus cannot not be excluded, PDT therapy is a reasonable treatment in this setting. The treatment involves the use of a light and drug combination that must be administered with close attention to dosimetry, since tissue effects of the therapy are delayed and cannot be observed at the time of treatment. Drug administration of sodium porfimer should precede photoradiation by 48 hours. Overall results with this treatment have been good. Case series have established a success rate of 88% to 100% in elimination of high-grade dysplasia. The only randomized multi-center prospective trial in the treatment of Barretts esophagus with high-grade dysplasia has established that the treatment eliminates high-grade dysplasia better than administration of proton pump inhibitors alone. Unfortunately, there are significant adverse events, including cutaneous photosensitivity, odynophagia, stricture formation, and lack of response.

Nonsurgical management of Barrett's esophagus with high-grade dysplasia

Endoscopic management options for BE with high-grade dysplasia consist of either surveillance methods or endoscopic mucosal ablative therapies. Intensive surveillance once a person is diagnosed with high-grade dysplasia may avoid an unneeded esophagectomy because it appears that most patients with high-grade dysplasia may not progress to esophageal adenocarcinoma. Only a single study has been presented that demonstrates that this approach does not lead to missed opportunities for intervention before progression to advanced stage disease [20]. This study excluded patients with cancer detected within 1 year of diagnosis of high-grade dysplasia; thus, patients who wish to proceed with an observation approach should be aware that the rate of missed esophageal adenocarcinomas ranges from 38% to 73%. The ability to observe a patient with high-grade dysplasia, however, does have appeal because a number of these patients appear to lose the high-grade dysplasia over time. The other endoscopic management option for Barretts esophagus with high-grade dysplasia is endoscopic mucosal ablative therapies. These include the KTP:YAG laser, the Nd:YAG laser, photodynamic therapy, and endoscopic mucosal resection. All ablative therapies are used in combination with control of gastroesophageal reflux. This allows the esophageal tissue to heal in an environment that is conducive to squamous mucosa. Although most are relatively small series with short durations of observation, they all have shown some promise in treating BE with high-grade dysplasia. These approaches have the advantage of eliminating the problem. The patient who is being observed must live with the thought of developing cancer. Patients who undergo successful ablation are returned to a normal life. The combination of therapies such as EMR with PDT may be the most promising approach to BE with high-grade dysplasia; however, the long-term effects of ablative therapy are not known and continued surveillance is still advised for this group of patients. The choice of a nonsurgical approach for the management of BE with high-grade dysplasia is ultimately up to the individual patient. All patients must be carefully informed of the treatment effects, possible outcomes, and the surgical alternative. Most patients who select nonsurgical approaches are either elderly or are not good surgical candidates. The choice is often affected by local expertise, as surgical procedures should be performed in centers with surgeons expert in esophagectomy. Nonsurgical approaches should also be performed by physicians who are familiar with their application. Future advances in nonsurgical techniques such as new photosensitizers in PDT and improvements in diagnostic techniques may allow patients a greater opportunity to preserve their esophagus.

Endoscopic Nd:YAG laser palliation of malignant duodenal tumors

This study assesses the outcome of 20 patients referred for neodymium: yttrium-aluminum-garnet laser therapy of malignant duodenal tumors between 1984 and 1992. Almost all (95%) of these patients required palliative therapy for gastrointestinal hemorrhage, and nearly half (45%) also had obstructive symptoms. A mean of 3 (range, 1 to 6) laser treatment sessions were required for palliation. Laser therapy eliminated the need for blood transfusions in only 38% of patients. Obstructive symptoms were improved in all patients after laser treatment. Treatment failure could not be predicted on the basis of demographic factors (other than age), tumor characteristics, or transfusion requirements. Survival after laser therapy was 30% at 6 months and 15% at 12 months. Endoscopic neodymium:yttrium-aluminum-garnet laser therapy is a reasonable approach for palliation of malignant tumor obstruction or hemorrhage in selected cases; however, hemorrhage often continues.

4557 Usefulness of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of neuroendocrine tumors not visualized by other imaging modalities.

Background: Suspicion of neuroendocrine tumors is often based on clinical symptoms and hormonal tests. To define the location of these tumors is difficult due to their small size at the time of diagnosis. EUS has been proven to be the most accurate method for diagnosis of small pancreatic tumors and small lesions of the duodenum wall. Nevertheless, to date, the role of EUS-FNA cytology for neuroendocrine tumor diagnosis has not been defined. Aim : Determine the utility of EUS-FNA in the diagnosis of small functioning neuroendocrine tumors not detected by other imaging modalities. Patients and Methods : From 1993 to 1999, 9 patients with clinical suspicion for neuroendocrine tumor underwent EUS-FNA to determine location and allow cytologic confirmation of the tumor. Mean age was 52 years (range 35-69) and male/female ratio was 4/5. Four patients presented with hypoglycemia, 2 with diarrhea and the remaining three had been diagnosed with Zollinger-Ellison syndrome. Three of these patients had a previously known MEN I syndrome. All patients had hormonal disturbances that strongly suggested the presence of a neuroendocrine tumor. EUS was routinely performed under conscious sedation with the mechanical radial instrument (Olympus GFUM 20 or GFUM 130) and, when the lesion was identified, FNA was performed under guidance with the curved linear array (Olympus GFUM 30P or Pentax FG 32UA). Results : EUS was able to visualize 13 tumors in these 9 patients (two out of three patients with known MEN I syndrome had two and four lesions respectively). In all but one patient CT did not show the tumor or missed at least one of the lesions. Two patients had exploratory surgery with intraoperative ultrasound prior to referral to our institution that failed to identify the tumor. Mean tumor size was 12 mm (range 4-25) and the tumor location was pancreas (n=12) or duodenal wall (n=1). EUS-FNA was performed in 11 of the 13 lesions detected. EUS-FNA accurately diagnosed neuroendocrine tumor in all cases. Seven patients underwent surgical resection confirming EUSFNA findings in all of them (accuracy 100%). No complications were observed. Conclusions : EUS is a highly accurate technique to visualize small size neuroendocrine tumors of those not seen on CT, this is specially important in those patients with multiple lesions. EUS-FNA safely provides cytologic confirmation with a high accuracy in these patients.

Does performance status influence the outcome of Nd:YAG laser therapy of proximal esophageal tumors?

The value of endoscopic palliative therapy for malignant obstruction in the proximal esophagus has been questioned. To assess the importance of pre-treatment performance status on treatment outcome, we reviewed the records of patients with tumors of the proximal esophagus undergoing endoscopic laser therapy between January 1986 and December 1988. As compared with 10 patients having a good performance status, eight patients with a poor performance status had a lower frequency of obtaining complete functional relief of dysphagia (14% versus 71%), an increased rate of complications (50% versus 0%), and a shorter median survival time (24 days versus 161 days). We conclude that performance status should be considered in determining the appropriateness of laser therapy in patients with proximal esophageal cancer.

Molecular Pathogenesis of Barrett Esophagus: Current Evidence

This article focuses on recent findings on the molecular mechanisms involved in esophageal columnar metaplasia. Signaling pathways and their downstream targets activate specific transcription factors leading to the expression of columnar and the more specific intestinal-type of genes, which gives rise to Barrett metaplasia. Several animal models have been generated to validate and study these distinct molecular pathways but also to identify the Barrett progenitor cell. Currently, the many aspects involved in the development of esophageal metaplasia that have been elucidated can serve to develop novel molecular therapies to improve treatment or prevent metaplasia. Nevertheless, several key events are still poorly understood and require further investigation.

4915 Long-term results of photodynamic therapy for barrett's esophagus.

Many mucosal ablative techniques have been used to treat Barretts esophagus but their long-term effects are unknown. Aim: To determine the longterm results of patients with Barretts esophagus treated by photodynamic therapy (PDT). Methods: Patients with documented Barretts esophagus confirmed by two experienced GI pathologists were entered into a photodynamic therapy trial. PDT was performed by administering intravenous hematoporphyrin derivative (HpD) at a dose of 1.75-4 mg/kg followed in 48 hours by endoscopy and photoradiation at a dose of 175-200 J/cm fiber using a 2.5 cm cylindrical diffusing fiber. Patients were treated with omperazole 40 mg a day for maintenance therapy. Patients have been prospectively followed with endoscopy performed with biopsies taken in 4 quadrants every centimeter throughout the length of the esophagus that was formerly occupied by Barrett s mucosa. Biopsies were also taken extensively from the squamocolumnar junction. Surveillance was performed at 3-6 month intervals dependent on the degree of dysplasia. We assessed patients who have had a minimum of 1 year of follow-up after PDT. Results: A total of 78 patients (63 males) with a mean age 61±1 years have been treated with PDT for Barretts esophagus and followed for a mean of 34±2 months. The initial Barretts segment was 7±1 cm in length that significantly decreased to 2±1 cm after an average 2 of treatments (p

Multimodality therapy for gastroesophageal cancers.

SummaryMultimodality therapy is the key to the treatment of carcinomas of the gastroesophageal junction. Chemoradiation followed by esophagectomy appears to be the standard therapy at the present time. Selected patients who respond completely to the chemotherapy and radiation are probably the best candidates for esophagectomy. Although extended lymph node dissection is advocated, there are not sufficient data to determine whether the increased morbidity of the procedure is justified by the improvement in outcome for junctional cancers. Early cancers in nonsurgical patients could potentially be treated by endoscopic methods including endoscopic mucosal resection, which permits accurate staging, and photodynamic therapy, which permits treatment of residual premalignant tissue. Palliation of patients with advanced cancers of the gastroesophageal junction is probably best managed with expandable metal stents, although there is some evidence to suggest that thermal methods of palliation may enhance the quality of life in these patients.