IU Indianapolis ScholarWorks :: Browsing by Author "DeWitt, John M."

Browsing by Author "DeWitt, John M."

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Assessment of Submucosal Distortion and Mass Effect Seen at Follow-up After Colorectal Endoscopic Mucosal Resection with ORISE
(Elsevier, 2022-05) Lahr, Rachel E.; DeWitt, John M.; Zhang, Dongwei; Rex, Douglas K.; Medicine, School of Medicine
Recovery from spinal cord injury (SCI) and other central nervous system (CNS) trauma is hampered by limits on axonal regeneration in the CNS. Regeneration is restricted by the lack of neuron-intrinsic regenerative capacity and by the repressive microenvironment confronting damaged axons. To address this challenge, we have developed a therapeutic strategy that co-targets kinases involved in both extrinsic and intrinsic regulatory pathways. Prior work identified a kinase inhibitor (RO48) with advantageous polypharmacology (co-inhibition of targets including ROCK2 and S6K1), which promoted CNS axon growth in vitro and corticospinal tract (CST) sprouting in a mouse pyramidotomy model. We now show that RO48 promotes neurite growth from sensory neurons and a variety of CNS neurons in vitro, and promotes CST sprouting and/or regeneration in multiple mouse models of spinal cord injury. Notably, these in vivo effects of RO48 were seen in several independent experimental series performed in distinct laboratories at different times. Finally, in a cervical dorsal hemisection model, RO48 not only promoted growth of CST axons beyond the lesion, but also improved behavioral recovery in the rotarod, gridwalk, and pellet retrieval tasks. Our results provide strong evidence for RO48 as an effective compound to promote axon growth and regeneration. Further, they point to strategies for increasing robustness of interventions in pre-clinical models.
Burkitt lymphoma presenting as multifocal doughnut-shaped masses in the stomach of a patient with AIDS
(Thieme, 2014) Sey, Michael Sai Lai; Czader, Magdalena; DeWitt, John M.
Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study
(Thieme, 2017-02) Yang, Dennis; Amin, Sunil; Gonzalez, Susana; Mullady, Daniel; Edmundowicz, Steven A.; DeWitt, John M.; Khashab, Mouen A.; Wang, Andrew Y.; Nagula, Satish; Buscaglia, Jonathan M.; Bucobo, Juan Carlos; Wagh, Mihir S.; Draganov, Peter V.; Stevens, Tyler; Vargo, John J.; Khara, Harshit S.; Diehl, David L.; Keswani, Rajesh N.; Komanduri, Srinadh; Yachimski, Patrick S.; Prabhu, Anoop; Kwon, Richard S.; Watson, Rabindra R.; Goodman, Adam J.; Benias, Petros; Carr-Locke, David L.; DiMaio, Christopher J.; Department of Medicine, IU School of Medicine
Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.
Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility
(Public Library of Science, 2014-03-20) Hocevar, Barbara A.; Kamendulis, Lisa M.; Pu, Xinzhu; Perkins, Susan M.; Wang, Zheng-Yu; Johnston, Erica L.; DeWitt, John M.; Li, Lang; Loehrer, Patrick J.; Klaunig, James E.; Chiorean, E. Gabriela; Medicine, School of Medicine
Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.
Development of a Multidisciplinary Program to Expedite Care of Esophageal Emergencies
(Elsevier, 2017-09) Ceppa, DuyKhanh P.; Rosati, Carlo Maria; Chabtini, Lola; Stokes, Samantha M.; Cook, Holly C.; Rieger, Karen M.; Birdas, Thomas J.; Lappas, John C.; Kessler, William R.; DeWitt, John M.; Maglinte, Dean D.; Kesler, Kenneth A.; Surgery, School of Medicine
Background Level 1 programs have improved outcomes by expediting the multidisciplinary care of critically ill patients. We established a novel level 1 program for the management of esophageal emergencies. Methods After institutional review board approval, we performed a retrospective analysis of patients referred to our level 1 esophageal emergency program from April 2013 through November 2015. A historical comparison group of patients treated for the same diagnosis in the previous 2 years was used. Results Eighty patients were referred and transported an average distance of 56 miles (range, 1–163 miles). Median time from referral to arrival was 2.4 hours (range, 0.4-12.9 hours). Referrals included 6 (7%) patients with esophageal obstruction and 71 (89%) patients with suspected esophageal perforation. Of the patients with suspected esophageal perforation, causes included iatrogenic (n = 26), Boerhaave’s syndrome (n = 32), and other (n = 13). Forty-six percent (n = 33) of patients were referred because of pneumomediastinum, but perforation could not be subsequently demonstrated. Initial management of patients with documented esophageal perforation included operative treatment (n = 25), endoscopic intervention (n = 8), and supportive care (n = 5). Retrospective analysis demonstrated a statistically significant difference in mean Pittsburgh severity index score (PSS) between esophageal perforation treatment groups (p < 0.01). In patients with confirmed perforations, there were 3 (8%) mortalities within 30 days. More patients in the esophageal level 1 program were transferred to our institution in less than 24 hours after diagnosis than in the historical comparison group (p < 0.01). Conclusions Development of an esophageal emergency referral program has facilitated multidisciplinary care at a high-volume institution, and early outcomes appear favorable.
The Dilemma of the Dilated Main Pancreatic Duct in the Distal Pancreatic Remnant After Proximal Pancreatectomy for IPMN
(Springer, 2019-08) Simpson, Rachel E.; Ceppa, Eugene P.; Wu, Howard H.; Akisik, Fatih; House, Michael G.; Zyromski, Nicholas J.; Nakeeb, Attila; Al-Haddad, Mohammad A.; DeWitt, John M.; Sherman, Stuart; Schmidt, C. Max; Surgery, School of Medicine
Objective(s) A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. Methods Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991–2016). Main-duct dilation included those ≥ 5 mm or “dilated” on radiographic reports. Statistics compared groups using Student’s T/Mann-Whitney U tests for continuous variables or chi-square/Fisher’s exact test for categorical variables with P < 0.05 considered significant. Results High-grade/invasive IPMN or adenocarcinoma at proximal pancreatectomy predicted malignant outcomes (100.0% malignant outcomes; P < 0.001) in remnant surveillance. Low/moderate-grade lesions revealed benign outcomes at last surveillance regardless of duct diameter. Twenty of 21 patients undergoing distal remnant reoperation had a dilated main duct. Seven had main-duct IPMN on remnant pathology; these patients had greater mean maximum main-duct diameter prior to reoperation (9.5 vs 6.2 mm, P = 0.072), but this did not reach statistical significance. Several features showed high sensitivity/specificity for remnant main-duct IPMN. Conclusions Remnant main-duct dilation after proximal pancreatectomy for IPMN remains a diagnostic dilemma. Several parameters show a promise in accurately diagnosing main-duct IPMN in the remnant.
Effectiveness and safety of serial endoscopic ultrasound–guided celiac plexus block for chronic pancreatitis
(Thieme Open, 2015-02) Sey, Michael S. L.; Schmaltz, Leslie; Al-Haddad, Mohammad A.; DeWitt, John M.; Calley, Cynthia S. J.; Juan, Michelle; Lasisi, Femi; Sherman, Stuart; McHenry, Lee; Imperiale, Thomas F.; LeBlanc, Julia K.; Medicine, School of Medicine
Background and study aims: Endoscopic ultrasound – guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. , Patients and methods: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. , Results: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 – 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 – 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred., Conclusions: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.
Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America
(Elsevier, 2020) Ngamruengphong, Saowanee; Ferri, Lorenzo; Aihara, Hiroyuki; Draganov, Peter V.; Yang, Dennis J.; Perbtani, Yaseen B.; Jue, Terry L.; Munroe, Craig A.; Boparai, Eshandeep S.; Mehta, Neal A.; Bhatt, Amit; Kumta, Nikhil A.; Othman, Mohamed O.; Mercado, Michael; Javaid, Huma; Aadam, Abdul Aziz; Siegel, Amanda; James, Theodore W.; Grimm, Ian S.; DeWitt, John M.; Novikov, Aleksey; Schlachterman, Alexander; Kowalski, Thomas; Samarasena, Jason; Hashimoto, Rintaro; Chehade, Nabil El Hage; Lee, John; Chang, Kenneth; Su, Bailey; Ujiki, Michael B.; Mehta, Amit; Sharaiha, Reem Z.; Carr-Locke, David L.; Chen, Alex; Chen, Michael; Chen, Yen-I.; Khoshknab, MirMilad Pourmousavi; Wang, Rui; Kerdsirichairat, Tossapol; Tomizawa, Yutaka; von Renteln, Daniel; Kumbhari, Vivek; Khashab, Mouen A.; Bechara, Robert; Karasik, Michael; Patel, Neej J.; Fukami, Norio; Nishimura, Makoto; Hanada, Yuri; Wong Kee Song, Louis M.; Laszkowska, Monika; Wang, Andrew Y.; Hwang, Joo Ha; Friedland, Shai; Sethi, Amrita; Kalloo, Antony N.; Medicine, School of Medicine
Background & Aims Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. Methods We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. Results Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. Conclusions ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.
Endoscopic ultrasound characteristics of pancreatic lymphoepithelial cysts: A case series from a large referral center.
(Wolters Kluwer, 2016) Dalal, Kunal S.; DeWitt, John M.; Sherman, Stuart; Cramer, Harvey M.; Tirkes, Temel; Al-Haddad, Mohammad A.; Department of Pathology and Laboratory Medicine, IU School of Medicine
BACKGROUND AND OBJECTIVES: Lymphoepithelial cysts (LECs) of the pancreas are benign lesions that can mimic cystic neoplasms on imaging. Endoscopic ultrasound (EUS) features have not been well described. We aimed to describe the clinical and EUS characteristics of LECs and the present outcomes of management at a high-volume referral center. MATERIALS AND METHODS: We identified patients who underwent EUS and were found to have LECs based on fine-needle aspiration (FNA) cytology or surgical pathology from existing databases. EUS features, imaging characteristics, and pathology results were described. RESULTS: Sixteen patients were found to have 17 LECs. The mean size was 33 mm ± 15 mm. Locations within the pancreas included 10 lesions in the tail, 3 in the body, 1 in the uncinate process; the remaining 3 were exophytic. Six lesions were anechoic, 6 were hypoechoic, and 5 had mixed echogenicity. Nine lesions had mixed solid/cystic components, 7 were purely cystic, and 1 was solid. Cyst fluid was thick or viscous in six cases and thin in three. Eleven patients had diagnostic cytopathology. Six patients ultimately underwent surgery due to symptoms, nondiagnostic FNA, or other clinical concerns for malignancy. CONCLUSIONS: Pancreatic LECs have variable morphology and echogenicity on EUS, but the appearance of a cyst with variable solid and cystic components combined with the appearance of thick, turbid, and viscous aspirate should raise suspicion for an LEC. The majority of patients with LECs at our center avoided surgery for LECs on the basis of diagnostic EUS-FNA.
Endoscopic Ultrasound Guided Treatment of Peristomal Varices
(Elsevier, 2023) Sarkis, Yara; Masuoka, Howard; Ghabril, Marwan; Gutta, Aditya; Al-Haddad, Mohammad A.; DeWitt, John M.; Medicine, School of Medicine
Background and aims The use of endoscopic ultrasound (EUS) for peristomal varices (PV) is limited to case reports. Methods Patients who underwent EUS-guided treatment of PV with cyanoacrylate (CYA) and/or coils between 04/2013 and 12/2019 were identified. All had failed previous therapies or had comorbidities precluding other options. Endoscopic technique, adverse events (AEs), rebleeding and repeat interventions were assessed. Results 20 patients (12 male, median: 62 years (IQR, 54.8-69.5) underwent initial EUS PV injection of CYA for secondary (n=19) or primary prophylaxis (n=1). Within 30 days, AEs occurred in 11 (55%) and 8 were mild. During a median 2.5 months (IQR, 2-8.5) follow-up, confirmed (n=6) or suspected (n=2) PV bleeding recurred; five of 8 recurrences were retreated with CYA and/or coils without AEs. After retreatment, PV bleeding recurred in two a median 6 months (IQR, 6-30) later. Conclusion EUS appears to be a safe and promising technique for treatment of PV.

Browsing by Author "DeWitt, John M."

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