Patrick Yachimski

Comprehensive Microscopy of the Esophagus in Human Patients with Optical Frequency Domain Imaging

BACKGROUND Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. OBJECTIVE The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients. DESIGN A pilot feasibility study. SETTING Massachusetts General Hospital. PATIENTS Twelve patients undergoing routine EGD. RESULTS Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. LIMITATIONS Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. CONCLUSIONS Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.

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.

Human Papillomavirus Community in Healthy Persons, Defined by Metagenomics Analysis of Human Microbiome Project Shotgun Sequencing Data Sets

ABSTRACT Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCE This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections.

Surgery in the Patient with Liver Disease

The advent of liver transplantation has greatly improved the long-term survival of patients with decompensated cirrhosis, and surgery is now performed more frequently in patients with advanced liver disease. The estimation of perioperative mortality is limited by the retrospective nature of and biased patient selection in the available clinical studies. The overall experience is that, in patients with cirrhosis, use of the Child classification and Model for End-Stage Liver Disease (MELD) score provides a reasonably precise estimation of perioperative mortality. Careful preoperative preparation and monitoring to detect complications early in the postoperative course are essential to improve outcomes.

Gastrointestinal bleeding in the elderly

Gastrointestinal bleeding affects a substantial number of elderly people and is a frequent indication for hospitalization. Bleeding can originate from either the upper or lower gastrointestinal tract, and patients with gastrointestinal bleeding present with a range of symptoms. In the elderly, the nature, severity, and outcome of bleeding are influenced by the presence of medical comorbidities and the use of antiplatelet medication. This Review discusses trends in the epidemiology and outcome of gastrointestinal bleeding in elderly patients. Specific causes of upper and lower gastrointestinal bleeding are discussed, and recommendations for approaches to endoscopic diagnosis and therapy are given.Gastrointestinal bleeding affects a substantial number of elderly people and is a frequent indication for hospitalization. Bleeding can originate from either the upper or lower gastrointestinal tract, and patients with gastrointestinal bleeding present with a range of symptoms. In the elderly, the nature, severity, and outcome of bleeding are influenced by the presence of medical comorbidities and the use of antiplatelet medication. This Review discusses trends in the epidemiology and outcome of gastrointestinal bleeding in elderly patients. Specific causes of upper and lower gastrointestinal bleeding are discussed, and recommendations for approaches to endoscopic diagnosis and therapy are given.

Patient Predictors of Esophageal Stricture Development After Photodynamic Therapy

BACKGROUND & AIMS The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barretts esophagus, are associated with post-PDT stricturing. METHODS Data from all patients who had undergone PDT with porfimer sodium for Barretts esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed. RESULTS One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007). There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barretts esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P = .025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barretts esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. CONCLUSIONS An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barretts esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT.

Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy.

BACKGROUND Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution. OBJECTIVE The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis. DESIGN A feasibility study. SETTING Gastrointestinal Unit, Massachusetts General Hospital. PATIENTS Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal. RESULTS The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barretts esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture. LIMITATIONS Ex vivo, descriptive study. CONCLUSIONS Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited.

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding: Effect of Standardized Guidelines on Prescribing Practice

BACKGROUND Proton pump inhibitors (PPIs) are frequently prescribed for prophylaxis of nosocomial upper gastrointestinal tract bleeding. Some inpatients receiving PPIs may have no risk factors for nosocomial upper gastrointestinal tract bleeding, and PPIs may be continued unnecessarily at hospital discharge. We aimed to assess the effect of standardized guidelines on PPI prescribing practices. METHODS Guidelines for PPI use were implemented on the medical service at a tertiary center. We reviewed PPI use among inpatient admissions during the month before implementation of guidelines and then prospectively evaluated PPI use among admissions during the month after implementation of guidelines. RESULTS Among an overall cohort of 942 patients, 48% were prescribed PPIs while inpatients, and 41% were prescribed PPIs at hospital discharge. Univariate predictors of inpatient PPI use included age, length of hospital stay, history of gastroesophageal reflux disease or upper gastrointestinal tract bleeding, and outpatient PPI, aspirin, or glucocorticoid use. Among patients not on an outpatient regimen of PPIs at admission, implementation of guidelines resulted in lower rates of inpatient PPI use (27% before vs 16% after, P = .001) and PPI prescription at discharge (16% before vs 10% after, P = .03). CONCLUSION Introduction of standardized guidelines resulted in lower rates of PPI use among a subset of inpatients and reduced the rate of PPI prescriptions at discharge.

Treatment of Barrett's esophagus with high-grade dysplasia or cancer: predictors of surgical versus endoscopic therapy

BACKGROUND & AIMS Patients with Barretts esophagus and high-grade dysplasia or intramucosal carcinoma are at risk of progression to invasive carcinoma. Both esophagectomy and endoscopic ablation are treatment options. The aim of this study was to identify predictors of surgical versus endoscopic therapy at a tertiary center. METHODS An institutional database identified patients with Barretts esophagus between 2003 and 2007. Demographic data and International Classification of Diseases-9th revision codes for esophagectomy, endoscopic ablation, as well as selected medical comorbidities were retrieved. Individual endoscopy, surgical, and pathology reports were reviewed. RESULTS Among 2107 individuals with Barretts esophagus, 79 underwent esophagectomy and 80 underwent endoscopic ablation. The mean age was 63.1 +/- 10.6 years in the surgical group and 69.7 +/- 9.4 years in the ablation group (P < .0001). Among high-grade dysplasia/intramucosal carcinoma patients, 9 of 76 (12%) first seen by a gastroenterologist underwent esophagectomy, whereas 18 of 21 (86%) first seen by a surgeon underwent esophagectomy. In a logistic regression model, factors associated independently with esophagectomy were as follows: patient age of 60 or younger (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.65-14.9), cancer stage T1sm or greater (OR, 16.0; 95% CI, 5.60-45.6), and initial consultation performed by a surgeon (vs gastroenterologist) (OR, 35.1; 95% CI, 9.58-129). CONCLUSIONS Patient age and cancer stage predict treatment modality for Barretts esophagus with neoplasia. Treatment choice is influenced further by whether the initial evaluation is performed by a gastroenterologist or a surgeon.