Cadman L Leggett

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (21)65 Total impact

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    ABSTRACT: Background & Aims Superficial (T1) esophageal adenocarcinoma (EAC) is commonly treated by endoscopic resection, yet little is known about factors that predict outcomes of this approach. We assessed clinical and histologic variables associated with overall survival times of patients with T1 EAC who received therapy. Methods In a retrospective analysis, we collected data from patients who underwent endoscopic mucosal resection (EMR) for T1 EAC (194 with T1a and 75 with T1b) at the Mayo Clinic, from 1995 through 2011. EMR specimens were systematically reviewed for depth of invasion, presence of lymphovascular invasion, grade of differentiation, and status of resection margins. Kaplan-Meier curves and proportional hazards regression models were used in statistical analyses. Results Demographic characteristics were similar between patients with T1a and T1b EAC. Overall survival at 5 years following EMR was 74.4% for patients with T1a (95% confidence interval [CI], 67.6%−81.8%) and 53.2% for patients with T1b EAC (95% CI 40.3%–70.1%). Of surviving patients with T1a EAC, 94.1% remained free of cancer (95% CI, 89.8%–98.5%), and 94.7% of surviving patients with T1b EAC remained free of cancer (95% CI, 85.2%−100%). A multivariable model associated older age (per 10-year increment), evidence of lymphovascular invasion, and deep margin involvement with reduced overall survival in patients with T1 EAC Conclusion Systematic assessment of EMR specimens can help predict mortality and potentially guide treatment options for patients with T1 EAC.
    Clinical Gastroenterology and Hepatology 08/2014; · 6.65 Impact Factor
  • The American Journal of Gastroenterology 02/2014; 109(2):298-9. · 9.21 Impact Factor
  • Article: Reply.
    Cadman L Leggett, Prasad G Iyer
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; · 5.64 Impact Factor
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    Annals of Gastroenterology 01/2014; 27(1):74.
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    Cadman L Leggett, Emmanuel C Gorospe
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    ABSTRACT: Confocal laser endomicroscopy is an advanced endoscopic imaging modality that can be used for the diagnosis of early mucosal dysplasia in various gastrointestinal conditions. It provides histology-like images at 1000-fold magnification. The technology offers potential advantages in the diagnosis of Barrett's esophagus and early esophageal cancer due to the low yield of the current practice of surveillance endoscopy with biopsies. Confocal laser endomicroscopy has the potential to eliminate the need for biopsy, establish diagnosis and facilitate application of endoscopic therapy during the time of actual endoscopy. There are several studies that have demonstrated reasonable diagnostic accuracy in patients undergoing surveillance for Barrett's esophagus from tertiary academic medical centers. However, the application of confocal laser endomicroscopy in routine clinical endoscopy is still in the process of refinement. Its role in the diagnosis and treatment of Barrett's-associated dysplasia will continue to evolve with improvement in technology, criteria for diagnosis and experience among endoscopists in interpreting confocal imaging.
    Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology. 01/2014; 27(3):193-199.
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    Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology. 01/2014; 27(4):409.
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    ABSTRACT: Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). Aims of this study were to assess the association between OSA and BE and determine if the association is independent of GERD and body mass index (BMI) METHODS: Patients who had undergone a diagnostic polysomnogram and an esophagogastroduodenoscopy were identified using Mayo Clinic (Rochester, Minnesota) databases from January 2000 through November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n=36), OSA but no BE (n=78), both (n=74), or neither (n=74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed using a multiple variable logistic model that incorporated age, sex, BMI, a clinical diagnosis of GERD, and smoking history. Subjects with OSA had an 80% increased risk for BE compared to subjects without OSA (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.2; P=.03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured using the Apnea Hypopnea Index (AHI), was associated with an increased risk of BE (OR, 1.2 per 10 units increase in AHI; 95% CI, 1.0-1.3; P=.03). In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2013; · 5.64 Impact Factor
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    ABSTRACT: To describe basic principles of tissue engineering with emphasis on the potential role of gastrointestinal endoscopy in regenerative medicine. Stricturing associated with endoscopic submucosal resection and circumferential endoscopic mucosal resection can be prevented through transplantation of autologous epidermal cell sheets or seeded decellularized biological scaffolds. Lower esophageal sphincter augmentation through injection of muscle-derived cells is a novel potential treatment for gastroesophageal reflux disease. Stem cell derived tissue has been used to repair injured colon in a mouse model of colitis. A bioengineered internal anal sphincter has been successfully implanted in mice and showed preserved functionality. The immediate foreseeable application of tissue engineering in gastrointestinal endoscopy is in the field of mucosal repair after acute injury. Tissue regeneration can be achieved through expansion of autologous somatic cells or by induction of multipotent or pluripotent stem cells. Advances in cellular scaffolding have made bioengineering of complex tissues a reality. Tissue engineering in endoscopy is also being pioneered by studies looking at enteral sphincter augmentation and regeneration. The availability of engineered tissue for endoscopic application will increase with advances in cell-culturing techniques.
    Current opinion in gastroenterology 07/2013; · 4.33 Impact Factor
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    ABSTRACT: Barrett's esophagus (BE) is the only established precursor lesion in the development of esophageal adenocarcinoma (EAC) and it increases the risk of cancer by 11-fold. It is regarded as a complication of gastroesophageal reflux disease. There is an ever-increasing body of knowledge on the pathogenesis, diagnosis, treatment, and surveillance of BE and its associated dysplasia. In this review, we summarize the latest advances in BE research and clinical practice in the past 2 years. It is critical to understand the molecular underpinnings of this disorder to comprehend the clinical outcomes of the disease. For clinical gastroenterologists, there is also continuous growth of endoscopic approaches which is daunting, and further improvements in the detection and treatment of BE and early EAC are anticipated. In the future, we may see the increased role of biomarkers, both molecular and imaging, in both diagnostic and therapeutic strategies for BE.
    Current Gastroenterology Reports 05/2013; 15(5):322.
  • Cadman L Leggett, Emmanuel C Gorospe, Kenneth K Wang
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    ABSTRACT: Endoscopic therapy for Barrett's esophagus is feasible and likely to decrease the future risk of development of esophageal adenocarcinoma. The most commonly used therapy is radiofrequency ablation, which has been shown to produce reproducible superficial injury in the esophagus. Other thermal therapies include multipolar coagulation, argon plasma coagulation, and thermal laser therapy. The other end of the ablative spectrum includes cryotherapy, which involves freezing tissue to produce mucosal necrosis. Photodynamic therapy has been used to photochemically eliminate abnormal mucosa. Endoscopic therapy has been demonstrated to be effective in high-risk situations such as Barrett's esophagus with high-grade dysplasia.
    Gastroenterology clinics of North America 03/2013; 42(1):175-85. · 2.56 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Positron Emission Tomography with Computed Tomography (PET/CT) has been used to detect metastasis in the diagnosis of esophageal adenocarcinoma (EAC). However, the utility of PET/CT to assess primary tumor for endoscopic resectability and prognosis in early EAC remains unclear. We conducted a retrospective study to determine the association of PET/CT findings with histopathological tumor invasion depth and survival outcomes. METHODS: EAC patients who underwent PET/CT followed by endoscopic mucosal resection (EMR) were included. We retrieved pathology on EMR and survival outcomes from a prospectively-maintained database. Two radiologists independently reviewed the PET/CT using the following parameters: detection of malignancy, fluorodeoxyglucose (FDG) uptake intensity, FDG focality, FDG eccentricity, esophageal thickness, maximal standard uptake value (SUVmax), and SUVmax ratio (lesion/liver). RESULTS: There were 72 eligible patients: 42 (58.3%) had T1a lesions and 30 (41.7%) had ≥ T1b. Only SUVmax ratio was associated with tumor invasion depth (OR = 2.77, 95% CI: 1.26-7.73, p = 0.0075). Using a cutoff of 1.48, the sensitivity and specificity of SUVmax ratio for identification of T1a lesions were 43.3% and 80.9%, respectively. Adjusting the SUVmax ratio to 2.14, 16.7% (5/30) of ≥ T1b patients were identified without any false positive cases. Multivariate analysis showed SUVmax ratio, Charlson comorbidity index, and esophagectomy were independent predictors for survival. CONCLUSIONS: SUVmax ratio (lesion/liver) is more accurate in predicting endoscopic resectability and mortality for EAC than other PET/CT parameters and appears promising as a useful adjunct to the current diagnostic workup.
    Journal of Gastroenterology and Hepatology 02/2013; · 3.33 Impact Factor
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    ABSTRACT: To assess the association between Barrett esophagus (BE) and the metabolic syndrome in patients with and without reflux symptoms and to determine whether this association is reflux independent and metabolically driven. Case patients with BE and controls were residents of Olmsted County, Minnesota (1999-2006). Two control groups (one with and one without symptoms of gastroesophageal reflux) were identified from a cohort of patients who had responded to a validated gastrointestinal symptom questionnaire. Cases and controls were individually matched by age, sex, and duration of follow-up. Controls did not have a known diagnosis of BE. The association of the metabolic syndrome and its individual components with BE was assessed using univariate and multivariate conditional logistic regression separately for each control group. A total of 309 patients were included (103 BE cases, 103 controls with reflux symptoms, and 103 controls without reflux symptoms). A total of 64% of cases, 47% of controls with reflux symptoms, and 50% of controls without reflux symptoms had the metabolic syndrome. The metabolic syndrome was associated with a 2-fold increased risk of BE relative to those with (odds ratio, 2.00; 95% CI, 1.10-3.65; P=.02) and without (odds ratio, 1.90; 95% CI, 1.03-3.60; P=.04) reflux symptoms. This association was independent of smoking, alcohol consumption, and body mass index and remained robust with sensitivity analysis. The metabolic syndrome is associated with BE independent of reflux symptoms, which may reflect a reflux-independent pathway of BE pathogenesis.
    Mayo Clinic Proceedings 02/2013; 88(2):157-65. · 5.79 Impact Factor
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    ABSTRACT: Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.
    Diseases of the Esophagus 01/2013; · 1.64 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is a potential treatment for pancreatic cancer. A second-generation photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide (HPPH) has a long wavelength absorption, high-tumor selectivity, and shorter duration of skin photosensitivity. We investigated the efficacy of PDT with HPPH and gemcitabine in inducing cell death in multiple pancreatic cancer cell lines. METHODS: We used three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BXPC-3) incubated with HPPH concentration of 0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, and 0.5 µg/ml for 6 hours, followed by photoradiation at a light dose of 60 J/cm(2) . Afterwards, each cell line was treated with gemcitabine at concentrations of 0, 1, 10, and 100 µM and incubated for another 96 hours. Cell death was detected with SYTOX green staining. We also assessed the difference in cytotoxicity in adding gemcitabine before and after PDT. RESULTS: HPPH-PDT can effectively induce cell death in all cell lines in a dose-dependent manner, with a 100% of cell death at the 0.5 µg/ml HPPH concentration. In contrast, monotherapy with gemcitabine alone (100 µM) only achieved <45% cell death. Combining gemcitabine to HPPH-PDT resulted in synergistic cytotoxic effect with 20-50% more cell death across all cell lines. There was no difference in cytotoxicity in adding gemcitabine before or after PDT. CONCLUSION: This is the first study on HPPH-PDT for pancreatic cancer. HPPH-PDT-induced cell death occurs in a dose-dependent manner. HPPH-PDT and gemcitabine have synergistic effects in inducing cell death in multiple pancreatic cancer cell lines. Lasers Surg. Med. © 2012 Wiley Periodicals, Inc.
    Lasers in Surgery and Medicine 09/2012; · 2.46 Impact Factor
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    ABSTRACT: There are currently 2 existing confocal laser endomicroscopy (CLE) platforms: probe-based CLE (pCLE) and endoscope-based CLE (eCLE) systems, each with its own criteria for identifying dysplasia in Barrett's esophagus (BE). The diagnostic performance of these 2 systems has not been directly compared. Preclinical, feasibility study. We compared the interrater agreement and diagnostic performance of the pCLE and eCLE systems. In addition, we evaluated a new BE endomicroscopy criteria based on fluorescent glucose intensity uptake. Thirteen patients with Barrett's esophagus and high-grade dysplasia or early cancer undergoing 16 EMR. CLE imaging was performed using two different probes with 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose, a fluorescent glucose analog with preferential uptake in dysplastic mucosa to supply contrast. Four quadrants were imaged per specimen with a total of 64 imaged mucosal sites presented to three gastroenterologists. Interobserver agreement and accuracy for dysplasia was assessed of images classified according to Miami criteria, stacked eCLE images classified using the Mainz criteria and a novel fluorescence intensity criteria. The interrater agreements were 0.17, 0.68, and 0.87 for the Miami, Mainz, and the fluorescence intensity criteria, respectively. Overall accuracy in detecting dysplasia was 37% (95% CI, 30.3-43.9), 44.3% (95% CI, 37.3-50.9), and 78.6% (95% CI, 72.2-83.3) for the Miami, Mainz, and the fluorescence intensity criteria, respectively. This imaging technique and proposed fluorescence intensity criteria using 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose in EMR tissue will require in vivo validation and cannot be directly used with the current eCLE and pCLE clinical applications. In this preclinical feasibility study, the use of an eCLE system with a topical fluorescent contrast in ex vivo EMR tissue demonstrated higher interrater agreement and accuracy.
    Gastrointestinal endoscopy 09/2012; 76(5):933-8. · 6.71 Impact Factor
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    ABSTRACT: Photodynamic therapy (PDT) with placement of a biliary stent may improve bile duct patency in patients with cholangiocarcinoma (CCA). We aimed to determine the effectiveness of biliary stenting with PDT compared to biliary stenting alone in the palliative treatment of CCA. Several databases were searched from inception to December 2011 for prospective studies comparing biliary stenting with PDT vs. biliary stenting only for CCA. Outcomes of interest included patient survival, quality of life (using Karnofsky score), and serum bilirubin levels. The relative risk (RR) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes were estimated using DerSimonian and Laird random-effects model. Inconsistency was quantified using I(2) statistics. The extent of publication bias was ascertained by visual inspection of funnel plots and Egger's test. There were six studies that met inclusion criteria. A total of 170 participants received PDT and 157 had biliary stenting only. Compared with biliary stenting, PDT was associated with a statistically significant increase in the length of survival (WMD 265 days; 95%CI: 154-376; p=0.01; I(2)=65%), improvement in Karnofsky scores (WMD 7.74; 95%CI: 3.73-11.76; p=0.01; I(2)=14%), and a trend for decline in serum bilirubin (WMD -2.92mg/dL; 95%CI: -7.54 to 1.71; p=0.22; I(2)=94%). The pooled event rate for biliary sepsis was 15% and was similar between PDT and control groups. Palliative treatment of CCA with PDT is associated with increased survival benefit, improved biliary drainage, and quality of life. However, the quality of this evidence is low.
    Photodiagnosis and photodynamic therapy 09/2012; 9(3):189-95.
  • Cadman L Leggett, Ganapathy A Prasad
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    ABSTRACT: Endoscopic eradication therapy is considered a well tolerated and effective alternative to esophagectomy for a select patient population with high-grade Barrett's esophagus and intramucosal adenocarcinoma. This review highlights the available eradication techniques (resection and ablation) with emphasis on factors that influence the choice of therapy. Long-term follow-up of patients treated with endoscopic eradication therapies demonstrates high rates of complete remission of dysplasia and intestinal metaplasia with overall survival comparable to patients treated surgically. Cohort studies also report that recurrence following successful ablation occurs in a significant proportion of patients, making careful surveillance an indispensable component following successful endoscopic therapy. Endoscopic eradication therapy is also effective for the treatment of recurrent dysplasia and intestinal metaplasia. Ablative therapies may lead to buried metaplasia in a small proportion of patients. The long-term clinical implications of buried metaplasia are unclear. Patients undergoing endoscopic eradication therapy should be enrolled in a comprehensive surveillance and staging program that offers both resection and ablative techniques. Complete remission of dysplasia and intestinal metaplasia can be achieved in the vast majority of patients undergoing endoscopic therapy. Surveillance should continue after treatment with close monitoring for recurrent dysplasia.
    Current opinion in gastroenterology 03/2012; 28(4):354-61. · 4.33 Impact Factor
  • Annals of Gastroenterology 01/2012; 25(2):166.
  • Emmanuel Cruz Gorospe, Cadman L Leggett
    Case Reports 01/2012; 2012.
  • Emmanuel C Gorospe, Cadman L Leggett, Gang Sun
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    ABSTRACT: A 59-year-old male presented with a 1-month history of intermittent diarrhea, abdominal pain, and hematochezia. He had a right hemicolectomy for cecal cancer 5 years ago. His radiologic and endoscopic surveillance have been negative. He had no other medical comorbidities. On presentation, he was hemodynamically stable. Laboratory studies were only significant for anemia (hemoglobin 10.2 g/dL) without evidence of thrombocytopenia or bleeding disorders. Stool studies were negative for infectious agents. A contrast-enhanced computed tomography of his abdomen showed bowel wall thickening from the rectum to the descending colon (Fig. 1). Colonoscopy demonstrated erythema and friable mucosa in the same segments. Colon biopsies revealed mucosal edema and prominent capillaries, consistent with a congestive process. A mesenteric angiogram demonstrated an arteriovenous malformation (AVM) arising from the superior rectal artery, a branch of the inferior mesenteric artery (Fig. 2). Following unsuccessful attempts at AVM embolization, the patient underwent a total proctocolectomy with end ileostomy. His recovery was uneventful with no recurrence of hematochezia. Inferior mesenteric AVMs are extremely rare with only 15 published cases in the English literature [1,2]. In a patient with prior abdominal surgery, AVM should be considered as a cause of ischemic colitis in the absence of other etiologies. AVMs can be classified as congenital or iatrogenic, secondary to abdominal trauma or colonic resection, as illustrated in our case [3]. Increased blood flow through an AVM can result in venous hypertension and decreased arterial flow, resulting in ischemia. In this case, the diagnosis of AVM was confirmed by mesenteric angiography. More recently, multidetector computed tomographic angiography has emerged as a safe, non-invasive, alternative vascular imaging for patients with mesenteric ischemia and AVM [2]. If treatment with embolization fails, colectomy may be necessary [1].
    Annals of Gastroenterology 01/2012; 25(2):165.

Publication Stats

65 Citations
65.00 Total Impact Points

Institutions

  • 2012–2014
    • Mayo Clinic - Rochester
      • Department of Gastroenterology and Hepatology
      Rochester, Minnesota, United States
    • Mayo Foundation for Medical Education and Research
      • Division of Gastroenterology and Hepatology
      Scottsdale, AZ, United States
  • 2012–2013
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China