James S. Barthel

Local Excision of T2 and T3 Rectal Cancers After Downstaging Chemoradiation

ObjectiveTo evaluate the safety and efficacy of local excision in patients with T2 and T3 distal rectal cancers that have been downstaged by preoperative chemoradiation. Summary Background DataT2 and T3 cancers treated by local excision alone are associated with unacceptably high recurrence rates. The authors hypothesized that preoperative chemoradiation might downstage both T2 and T3 lesions and significantly expand the indications for local excision. MethodsLocal excision was performed after preoperative chemoradiation on patients with a complete clinical response or on patients who were either ineligible for or refused to undergo abdominoperineal resection. Local excision was approached transanally by removing full-thickness rectal wall and the underlying mesorectum. ResultsFrom 1994 to 2000, 95 patients with rectal cancers underwent preoperative chemoradiation and surgical resection for curative intent. Of these, 26 patients (28%), 19 men and 7 women, with a mean age of 63 years (range 44–90), underwent local excision. Pretreatment endoscopic ultrasound classifications included 5 T2N0, 13 T3N0, 7 T3N1, and 1 not done. Pathologic partial and complete responses were achieved in 9 of 26 (35%) and 17 of 26 (65%) patients, respectively. Two of nine partial responders underwent immediate abdominoperineal resection. The mean follow-up was 24 months (median 19, range 6–77). The only recurrence was in a patient who refused to undergo abdominoperineal resection after a partial response. There was one postoperative death from a stroke. This treatment was associated with a low rate of complications. ConclusionLocal excision appears to be an effective alternative treatment to radical surgical resection for a highly select subset of patients with T2 and T3 adenocarcinomas of the distal rectum who show a complete pathologic response to preoperative chemoradiation.

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.

Dedifferentiation Precedes Invasion in the Progression from Barrett's Metaplasia to Esophageal Adenocarcinoma

Purpose: Adenocarcinoma arises in Barretts esophagus by progression from metaplasia to cancer through grades of dysplasia. Our aim in this exploratory study was to characterize the broad changes in gene expression that underlie this histologic progression to cancer and assess the potential for using these gene expression changes as a marker predictive of malignant progression in Barretts epithelium. Experimental Design: Microarray analysis was used to obtain individual gene expression profiles from endoscopic biopsies of nine esophageal adenocarcinomas and the Barretts epithelia from which three of the cancers had arisen. Pooled samples from the Barretts epithelia of six patients without cancer or dysplasia served as a reference. Results: Barretts epithelia from which cancer had arisen differed from the reference Barretts epithelia primarily by underexpression of genes, many of which function in governing cell differentiation. These changes in gene expression were found even in those specimens of Barretts epithelia from which cancer had arisen that lacked dysplasia. Each cancer differed from the Barretts epithelium from which it had arisen primarily by an overexpression of genes, many of which were associated with tissue remodeling and invasiveness. Cancers without identifiable Barretts epithelium differed from cancers that had arisen from a Barretts epithelium by having an even greater number of these overexpressed genes. Conclusions: Histologic progression from Barretts epithelium to cancer is associated with a gradient of increasing changes in gene expression characterized by an early loss of gene function governing differentiation that begins before histologic change; gain in function of genes related to remodeling and invasiveness follows later. This correlation of histologic progression with increasing changes in gene expression suggests that gene expression changes in biopsies taken from Barretts epithelium potentially could serve as a marker for neoplastic progression that could be used to predict risk for developing cancer.

Management of persistent gastroesophageal anastomotic strictures with removable self-expandable polyester silicon-covered (Polyflex) stents: an alternative to serial dilation.

BACKGROUND A benign gastroesophageal anastomotic stricture occurs in up to 42% of patients after transhiatal esophagectomy for esophageal cancer. Management of anastomotic strictures may require extended periods of serial endoscopic dilation, with significant risk, cost, and inconvenience for the patient. OBJECTIVE To determine if placement of removable self-expandable polyester silicon-covered (Polyflex) stents (SEPSs) prolonged the interval between endoscopic interventions in the management of persistent anastomotic stricture. DESIGN Retrospective cohort study. SETTING National Cancer Institute designated comprehensive cancer center. PATIENTS Eight patients after a transhiatal esophagectomy referred for management of benign persistent anastomotic strictures. INTERVENTIONS Serial balloon and bougie dilations and SEPS placement. MAIN OUTCOME MEASUREMENT The interval between endoscopic interventions and the number of endoscopic interventions before and after SEPS placement. RESULTS Over a 365-day period, 13 SEPS were placed in 8 patients with benign persistent anastomotic strictures after a transhiatal esophagectomy. A SEPS placement delayed the interval between endoscopic interventions from a mean of 7 days before stent insertion to 62 days after insertion (P < .008). The median number of preinsertion interventions was 4 and was reduced to 1 after insertion (P < .005). LIMITATION The small number of patients. CONCLUSIONS A SEPS placement did not result in stricture resolution or stabilization after SEPS removal. The SEPS migration rate was much higher in our patients with postesophagectomy anastomotic strictures than previously reported for other types of strictures. However, a SEPS placement did significantly delay the interval between endoscopic interventions in patients with persistent gastroesophageal anastomotic strictures after transhiatal esophagectomy. SEPS placement should be considered as an alternative to continued serial dilation in patients with persistent anastomotic strictures after transhiatal esophagectomy.

Early accidental dislodgement of PEG tubes

Newer percutaneous endoscopy gastrostomy (PEG) tubes with soft internal bolsters may be prone to accidental dislodgement or removal by patients. When this occurs after a mature gastrocutaneous fistula has formed, it is of little consequence as long as a replacement tube is promptly reinserted before the track closes. Blind reinsertion of a replacement tube before the track is adequately mature may have serious consequences, as exemplified by a patient who developed peritonitis as a result of inadvertent insertion into the peritoneal cavity. We managed two other patients with early accidental PEG tube removal by a period of nasogastric (NG) suction, intravenous antibiotic drugs, and observation, with a new tube placed endoscopically 7-9 days later. We review the management of early, inadvertent dislodgement of PEG tubes.

Current and evolving strategies for colorectal cancer screening

BACKGROUND Colorectal cancer is a major cause of cancer mortality and morbidity. Screening can potentially prevent most colorectal cancers by detection and removal of precursor adenomas. METHODS The literature and clinical practice guidelines are reviewed, with an emphasis on advances of the last 10 years and evolving screening methods. RESULTS Colonoscopy has come to be used for screening in persons at average risk for colorectal cancer because of the comparative ineffectiveness of other methods, although these methods continue to be recommended. Virtual colonoscopy and fecal DNA testing are emerging technologies with promise to be more effective than fecal occult blood testing or sigmoidoscopy in selecting those persons who should undergo colonoscopy. Next to age, family history is the most common risk factor for colorectal cancer and one that warrants more aggressive screening and, in some instances, genetic counseling and testing. Hereditary nonpolyposis colorectal cancer accounts for as many as 1 in 20 colorectal cancers, but to take advantage of recent advances in genetic testing for this disorder, a high level of clinical suspicion must be maintained. CONCLUSIONS If we are to reduce mortality and morbidity from colorectal cancer, practicing clinicians need to be aware of current and evolving strategies for colorectal screening, and assertively recommend the appropriate strategy to their patients.

Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

PURPOSE Fiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT. METHODS An institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers. RESULTS We identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present post-treatment imaging at a median of 107 days (range, 33-471 days) after implantation. CONCLUSIONS EUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques.

The effect of droperidol on objective markers of patient cooperation and vital signs during esophagogastroduodenoscopy: a randomized, double-blind, placebo-controlled, prospective investigation☆☆☆

We investigated the effect of droperidol on objective markers of cooperation and vital signs in 140 patients undergoing elective diagnostic esophagogastroduodenoscopy. Procedure duration and the total doses of midazolam and meperidine required during the procedure were evaluated as objective markers of patient cooperation. The droperidol group comprised 66 patients and the placebo group 74 patients. Patient and procedure characteristics were similar for both groups. Droperidol produced a 10% reduction in procedure duration. Linear multiple regression modeling revealed droperidol to be a significant predictor of procedure duration (p = .036). Droperidol significantly reduced midazolam and meperidine requirements (p < .01). Nonetheless, four patients in the droperidol group received naloxone to reverse prolonged, excessive drowsiness. Droperidol produced a significant reduction in procedure-associated increase in pulse rate but did not exacerbate procedure-associated reduction in mean arterial pressure. Droperidol favorably influences markers of patient cooperation during elective, diagnostic esophagogastroduodenoscopy. However, the clinical significance of these changes is unclear.

Anaplastic and sarcomatoid carcinoma of the small intestine: an unusual tumor.

Primary malignant tumors of the small intestine are rare, and sarcomatoid carcinomas have rarely been reported at this site. Anaplastic and sarcomatoid carcinomas are well described in the upper aerodigestive tract, particularly in the esophagus and the larynx. The authors report a case of anaplastic and sarcomatoid carcinoma of the ileum presenting as gastrointestinal bleeding. Their patient and the literature suggest that these tumors are much more aggressive than other small intestinal tumors. The importance of a systematic diagnostic approach in diagnosing these tumors is also discussed.

Cryoablation of persistent Barrett's epithelium after definitive chemoradiation therapy for esophageal adenocarcinoma

BACKGROUND Dysplastic Barretts epithelium (BE) persists after chemoradiation therapy for esophageal adenocarcinoma (EAC) arising in Barretts esophagus. This phenomenon may present a significant risk for development of metachronous adenocarcinoma. OBJECTIVE To analyze the safety and efficacy of endoscopic cryoablation therapy for persistent dysplastic BE in patients with complete clinical response after definitive chemoradiation therapy for EAC. DESIGN Retrospective cohort study. SETTING Single National Cancer Institute Comprehensive Cancer Center experience. PATIENTS Radiation and endoscopic oncology treatment records were reviewed between January 2004 and September 2009. Fourteen patients with EAC who had been treated with definitive chemoradiation therapy followed by cryoablation were identified. INTERVENTION Cryoablation therapy. MAIN OUTCOME MEASUREMENTS Reduction in Prague Classification and dysplasia status following cryoablation therapy. Complications reported at 24 hour after the procedure telephone survey and at subsequent endoscopy. RESULTS After complete clinical response of EAC to chemoradiation therapy, the median length of persistent BE was Prague classification C1M4 (C = circumferential extent, M = maximal extent). Cryoablation reduced the median length of persistent BE to Prague classification C0M1 (P = .009 with respect to circumferential extent and P = .004 with respect to maximal extent of BE). All 14 patients had dysplastic BE. Cryoablation resulted in histological downgrading in all 14 patients. Among patients with high-grade dysplasia, 20% (2/10) were reduced to low-grade dysplasia, 60% (6/10) to BE with no dysplasia, and 20% (2/10) to no BE. Among patients with low-grade dysplasia, 75% (3/4) were reduced to BE with no dysplasia, and 25% (1/4) to no BE. The median number of cryoablation treatments administered to the 14 patients evaluated was 1 (mean 1.5, range 1-5). Eighty-six percent (12/14) of patients reported no complaints during the 24 hours after cryoablation. No occurrences of perforation and no esophageal strictures were reported at surveillance endoscopy. LIMITATIONS Single-center, retrospective design involving a small number of patients. CONCLUSION Our observations suggest that cryoablation therapy is safe and effective for the treatment of persistent BE after definitive chemoradiation.