Letters to the Editor
2.
3.
4.
5.
6.
7.
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stent change intervals. Gastrointest Endosc 2010;72:558–63. Schilling D, Rink G, Arnold JC et al. Prospective, randomized, single-center trial comparing 3 different 10F plastic stents in malignant mid and distal bile duct strictures. Gastrointest Endosc 2003;58:54–8. Loew BJ, Howell DA, Sanders MK et al. Comparative performance of uncoated, selfexpanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial. Gastrointest Endosc 2009;70: 445–53. Kullman E, Frozanpor F, Soderlund C et al. Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. Gastrointest Endosc 2010;72:915–23. Telford JJ, Carr-Locke DL, Baron TH et al. A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. Gastrointest Endosc 2010;72:907–14. Menon K, Romagnuolo J, Barkun AN. Expandable metal biliary stenting in patients with recurrent premature polyethylene stent occlusion. Am J Gastroenterol 2001;96: 1435–40. Ito K, Fujita N, Noda Y et al. Is placement of two 10-Fr plastic stents (doublelayer) superior to single stent placement for the palliation of unresectable malignant biliary stricture? Gastrointest Endosc 2007;65:AB226. Park SB, Kim HW, Kang DH et al. Metallic or plastic stent for bile duct obstruction in ampullary cancer? Dig Dis Sci 2012;57: 786–90. Pola S, Muralimohan R, Cohen B et al. Longterm risk of cholangitis in patients with metal stents for malignant biliary obstruction. Dig Dis Sci 2012;57:2693–6.
1
Medical University of South Carolina, Charleston, South Carolina, USA. Correspondence: Christopher Lawrence, MD, Medical University of South Carolina, 7floor ART, Courtenay Drive, Charleston 29425, USA. E-mail: PANCBILIARY@ gmail.com
A Case of Rothia dentocariosa Bacteremia in a Patient Receiving Infliximab for Ulcerative Colitis Darwin F. Yeung, MD1, Ashkan Parsa, MD1, John C. Wong, MD2, Nazira Chatur, MD2, and Baljinder Salh, MD2 doi:10.1038/ajg.2013.366
© 2014 by the American College of Gastroenterology
To the Editor: Biologic agents that inhibit tumor necrosis factor (TNF)-alpha induce and maintain remission in autoimmune conditions, such as inflammatory bowel disease (IBD). However, their immunosuppressive effects can make patients susceptible to opportunistic infections (1). Rothia dentocariosa is a pleomorphic, aerobic and facultative anaerobic, gram-positive bacterium found predominantly in the normal flora of the human oral cavity. The potential for this commensal bacterium to cause clinically significant infection is becoming increasingly recognized. Aside from local periodontal infection, endocarditis is the most commonly reported systemic infection caused by R. dentocariosa, followed by septicemia, peritoneal dialysis-related peritonitis, and pneumonia (2). We describe a case of R. dentocariosa bacteremia in a patient with ulcerative colitis (UC) treated with the TNF-alpha antagonist, infliximab. A 42-year-old gentleman with UC was admitted to hospital in May 2013 after 2 months of increased bowel movements and abdominal pain. He was first diagnosed with UC in 1998. During the next 8 years, he had recurrent exacerbations in the setting of non-adherence to a combination of steroids, azathioprine, and 5-ASA and required frequent treatment with intravenous steroids and total parenteral nutrition. In 2006, he received four doses of infliximab. He nevertheless relapsed with extensive colitis involving three-quarters of his colon and underwent a total colectomy and ileostomy followed by an ileal pouchanal anastomosis in 2008. Over the next 4 years, he experienced only mild exacerbations until 2012 when he developed severe pouchitis extending into the small bowel. Budesonide and 6-mercaptopurine (MP) had minimal effect and were abandoned for a repeat trial of infliximab in January 2013, which induced remission. Unfortunately, in March 2013, he developed up to 10 bloody bowel movements per day including nocturnal episodes associated with abdominal pain, nausea, and vomiting. Worsening symptoms prompted admission to hospital 2 months later. By that time, he had received three doses of infliximab since re-initiation of therapy, with his last dose 2 weeks prior to admis-
sion. On admission, he was afebrile, hemodynamically stable, and his abdomen was mildly tender. He demonstrated good oral hygiene with no carious lesions. There were no signs of endocarditis. He had a peripherally inserted central catheter (PICC) for his infliximab infusions. Investigations revealed a normal white count at 9.5 but an elevated C-reactive protein at 124. Stool cultures, ova and parasites, and Clostridium difficile assay were negative. Blood cultures on admission grew R. dentocariosa in both the aerobic and anaerobic bottles sensitive to ceftriaxone, penicillin G, and vancomycin. Flexible sigmoidoscopy showed aphthous ulcers, mucosal edema, and erythema within the ileal pouch, especially proximally. In addition to intravenous steroids and 6-MP, he was treated empirically with ciprofloxacin and metronidazole on admission but switched to vancomycin on day 4 based on sensitivities. As repeat blood cultures on day 3 were negative and an echocardiogram showed no evidence of endocarditis, he was stepped down to amoxicillin-clavulanate the following day and his PICC was replaced with a Port-aCath. Once his bowel movements returned to baseline, the patient was discharged with oral steroids, 6-MP, and a 2-week course of amoxicillin-clavulanate. To our knowledge, this is the first reported case of R. dentocariosa bacteremia in an immunosuppressed patient receiving infliximab for UC. R. dentocariosa infections have been described in other immunosuppressed patients with acute myelocytic leukemia (3), chronic lymphocytic leukemia (4), and post-renal transplant lymphoproliferative disorder (5). Septic arthritis caused by R. dentocariosa has also been reported in a patient with rheumatoid arthritis treated with the TNF-alpha inhibitor, etanercept (6). Unlike infliximab, however, etanercept is a soluble TNF receptor with efficacy against rheumatoid arthritis but not IBD (7). Our case illustrates the potential of TNF-alpha inhibitors, including infliximab, to predispose patients toward clinically significant R. dentocariosa infection. CONFLICT OF INTEREST
The authors declare no conflict of interest.
The American Journal of GASTROENTEROLOGY
297
298
Letters to the Editor
REFERENCES 1. Lichtenstein G, Feagan B, Cohen R et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol 2012;107:1409–22. 2. Salamon SA, Prag J. Three cases of Rothia dentocariosa bacteraemia: frequency in Denmark and a review. Scand J Infect Dis 2002;34:153–7. 3. Schiff MJ, Kaplan MH. Rothia dentocariosa pneumonia in an immunocompromised patient. Lung 1987;165:279–82. 4. Pers C, Kristiansen JE, Jønsson V et al. Rothia dentocariosa septicaemia in a patient with chronic lymphocytic leukaemia and toxic granulocytopenia. Dan Med Bull 1987;34:322–3. 5. Wiesmayr S, Stelzmueller I, Berger N et al. Rothia dentocariosa sepsis in a pediatric renal transplant recipient having post-transplant lymphoproliferative disorders. Pediatr Transplant 2006;10:377–9. 6. Favero M, Raffeiner B, Cecchin D et al. Septic arthritis caused by Rothia dentocariosa in a patient with rheumatoid arthritis receiving etanercept therapy. J Rheumatol 2009;36:2846–7. 7. Rutgeerts P, Sandborn WJ, Feagan BG et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462–76. 1
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 2 Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Correspondence: Baljinder Salh, MD, Division of Gastroenterology, Department of Medicine, Gordon & Leslie Diamond Health Care Ctr., 5th Floor, 2775 Laurel Street, Vancouver, British Columbia, Canada V5Z 1M9. E-mail: [email protected]
ing in the background of high-grade dysplasia at the gastroesophageal junction. He was treated with a combination of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) and achieved complete eradication of intestinal metaplasia. Surveillance biopsies obtained a year following his last RFA treatment showed moderately differentiated IMC identified under squamous epithelium (SE) at a site close in location to his previous cancer. This was not seen on a high-resolution white light endoscopy and was only detected on mapping biopsies. A subsequent EMR was performed over an area of normal-appearing mucosa corresponding to the prior biopsy site. Histopathology demonstrated moderate to poorly differentiated IMC invading into the lamina propria and muscularis mucosa with negative mucosal and submucosal margins for cancer (Figure 1). Endoscopic ultrasound did not show evidence of esophageal wall thickening or regional lymphadenopathy. Imaging with confocal laser endomicroscopy (CLE) and volumetric laser endomicroscopy (VLE) was performed on the EMR specimen immediately following resection to ensure visualization of identical areas. Surface imaging with CLE using the fluorescent glucose analog 2-NBDG showed
a homogenous layer of SE (1). Cross-sectional imaging with VLE demonstrated BE with features suggestive of IMC, including increased signal intensity (black arrow) with numerous atypical-appearing glands and dilated ducts (white arrows) underneath a layer of SE (Figure 2). Subsquamous BE is found in ~0.9% of surveillance biopsies following RFA (2). Most of the time, subsquamous BE is nondysplastic but cancer has clearly been found in multiple series and presents a challenging diagnosis (3). VLE is a second-generation optical coherence tomography device that can generate in-vivo three-dimensional views of the human esophagus (4). Advantages of VLE over CLE are the capacity to perform wide-field imaging and the ability to visualize deeper into the mucosa (Supplementary Figures S1–S3 online). After ablative therapy for BE, it is essential to perform careful mapping biopsies of the mucosa to detect these small areas of residual cancer. This is the first case reported where VLE could clearly detect subsquamous Barrett’s adenocarcinoma, which was not seen by routine white light endoscopy or CLE. The use of in-vivo VLE has the potential to enhance the diagnosis of subsquamous BE and associated neoplasia.
Volumetric Laser Endomicroscopy Detects Subsquamous Barrett’s Adenocarcinoma Cadman L. Leggett, MD1, Emmanuel Gorospe, MD1, Victoria L. Owens, MD2, Marlys Anderson, BS1, Lori Lutzke, CCRP1 and Kenneth K. Wang, MD1
1 mm
Figure 1. Endoscopic mucosal resection showing subsquamous moderate to poorly differentiated adenocarcinoma invading into the lamina propria and muscularis mucosa.
SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg
doi: 10.1038/ajg.2013.422
SE IMC
To the Editor: A 74-year-old patient with Barrett’s esophagus (BE) (C5M5) enrolled in a surveillance program was found to have intramucosal adenocarcinoma (IMC) arisThe American Journal of GASTROENTEROLOGY
1 mm
Figure 2. Volumetric laser endomicroscopy of endoscopic mucosal resection with features suggestive of intramucosal adenocarcinoma (IMC), including increased signal intensity (black arrow) with atypical appearing glands and dilated ducts (white arrows) underneath a layer of squamous epithelium (SE).
VOLUME 109 | FEBRUARY 2014 www.amjgastro.com
2.
3.
4.
5.
6.
7.
8.
9.
stent change intervals. Gastrointest Endosc 2010;72:558–63. Schilling D, Rink G, Arnold JC et al. Prospective, randomized, single-center trial comparing 3 different 10F plastic stents in malignant mid and distal bile duct strictures. Gastrointest Endosc 2003;58:54–8. Loew BJ, Howell DA, Sanders MK et al. Comparative performance of uncoated, selfexpanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial. Gastrointest Endosc 2009;70: 445–53. Kullman E, Frozanpor F, Soderlund C et al. Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. Gastrointest Endosc 2010;72:915–23. Telford JJ, Carr-Locke DL, Baron TH et al. A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. Gastrointest Endosc 2010;72:907–14. Menon K, Romagnuolo J, Barkun AN. Expandable metal biliary stenting in patients with recurrent premature polyethylene stent occlusion. Am J Gastroenterol 2001;96: 1435–40. Ito K, Fujita N, Noda Y et al. Is placement of two 10-Fr plastic stents (doublelayer) superior to single stent placement for the palliation of unresectable malignant biliary stricture? Gastrointest Endosc 2007;65:AB226. Park SB, Kim HW, Kang DH et al. Metallic or plastic stent for bile duct obstruction in ampullary cancer? Dig Dis Sci 2012;57: 786–90. Pola S, Muralimohan R, Cohen B et al. Longterm risk of cholangitis in patients with metal stents for malignant biliary obstruction. Dig Dis Sci 2012;57:2693–6.
1
Medical University of South Carolina, Charleston, South Carolina, USA. Correspondence: Christopher Lawrence, MD, Medical University of South Carolina, 7floor ART, Courtenay Drive, Charleston 29425, USA. E-mail: PANCBILIARY@ gmail.com
A Case of Rothia dentocariosa Bacteremia in a Patient Receiving Infliximab for Ulcerative Colitis Darwin F. Yeung, MD1, Ashkan Parsa, MD1, John C. Wong, MD2, Nazira Chatur, MD2, and Baljinder Salh, MD2 doi:10.1038/ajg.2013.366
© 2014 by the American College of Gastroenterology
To the Editor: Biologic agents that inhibit tumor necrosis factor (TNF)-alpha induce and maintain remission in autoimmune conditions, such as inflammatory bowel disease (IBD). However, their immunosuppressive effects can make patients susceptible to opportunistic infections (1). Rothia dentocariosa is a pleomorphic, aerobic and facultative anaerobic, gram-positive bacterium found predominantly in the normal flora of the human oral cavity. The potential for this commensal bacterium to cause clinically significant infection is becoming increasingly recognized. Aside from local periodontal infection, endocarditis is the most commonly reported systemic infection caused by R. dentocariosa, followed by septicemia, peritoneal dialysis-related peritonitis, and pneumonia (2). We describe a case of R. dentocariosa bacteremia in a patient with ulcerative colitis (UC) treated with the TNF-alpha antagonist, infliximab. A 42-year-old gentleman with UC was admitted to hospital in May 2013 after 2 months of increased bowel movements and abdominal pain. He was first diagnosed with UC in 1998. During the next 8 years, he had recurrent exacerbations in the setting of non-adherence to a combination of steroids, azathioprine, and 5-ASA and required frequent treatment with intravenous steroids and total parenteral nutrition. In 2006, he received four doses of infliximab. He nevertheless relapsed with extensive colitis involving three-quarters of his colon and underwent a total colectomy and ileostomy followed by an ileal pouchanal anastomosis in 2008. Over the next 4 years, he experienced only mild exacerbations until 2012 when he developed severe pouchitis extending into the small bowel. Budesonide and 6-mercaptopurine (MP) had minimal effect and were abandoned for a repeat trial of infliximab in January 2013, which induced remission. Unfortunately, in March 2013, he developed up to 10 bloody bowel movements per day including nocturnal episodes associated with abdominal pain, nausea, and vomiting. Worsening symptoms prompted admission to hospital 2 months later. By that time, he had received three doses of infliximab since re-initiation of therapy, with his last dose 2 weeks prior to admis-
sion. On admission, he was afebrile, hemodynamically stable, and his abdomen was mildly tender. He demonstrated good oral hygiene with no carious lesions. There were no signs of endocarditis. He had a peripherally inserted central catheter (PICC) for his infliximab infusions. Investigations revealed a normal white count at 9.5 but an elevated C-reactive protein at 124. Stool cultures, ova and parasites, and Clostridium difficile assay were negative. Blood cultures on admission grew R. dentocariosa in both the aerobic and anaerobic bottles sensitive to ceftriaxone, penicillin G, and vancomycin. Flexible sigmoidoscopy showed aphthous ulcers, mucosal edema, and erythema within the ileal pouch, especially proximally. In addition to intravenous steroids and 6-MP, he was treated empirically with ciprofloxacin and metronidazole on admission but switched to vancomycin on day 4 based on sensitivities. As repeat blood cultures on day 3 were negative and an echocardiogram showed no evidence of endocarditis, he was stepped down to amoxicillin-clavulanate the following day and his PICC was replaced with a Port-aCath. Once his bowel movements returned to baseline, the patient was discharged with oral steroids, 6-MP, and a 2-week course of amoxicillin-clavulanate. To our knowledge, this is the first reported case of R. dentocariosa bacteremia in an immunosuppressed patient receiving infliximab for UC. R. dentocariosa infections have been described in other immunosuppressed patients with acute myelocytic leukemia (3), chronic lymphocytic leukemia (4), and post-renal transplant lymphoproliferative disorder (5). Septic arthritis caused by R. dentocariosa has also been reported in a patient with rheumatoid arthritis treated with the TNF-alpha inhibitor, etanercept (6). Unlike infliximab, however, etanercept is a soluble TNF receptor with efficacy against rheumatoid arthritis but not IBD (7). Our case illustrates the potential of TNF-alpha inhibitors, including infliximab, to predispose patients toward clinically significant R. dentocariosa infection. CONFLICT OF INTEREST
The authors declare no conflict of interest.
The American Journal of GASTROENTEROLOGY
297
298
Letters to the Editor
REFERENCES 1. Lichtenstein G, Feagan B, Cohen R et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol 2012;107:1409–22. 2. Salamon SA, Prag J. Three cases of Rothia dentocariosa bacteraemia: frequency in Denmark and a review. Scand J Infect Dis 2002;34:153–7. 3. Schiff MJ, Kaplan MH. Rothia dentocariosa pneumonia in an immunocompromised patient. Lung 1987;165:279–82. 4. Pers C, Kristiansen JE, Jønsson V et al. Rothia dentocariosa septicaemia in a patient with chronic lymphocytic leukaemia and toxic granulocytopenia. Dan Med Bull 1987;34:322–3. 5. Wiesmayr S, Stelzmueller I, Berger N et al. Rothia dentocariosa sepsis in a pediatric renal transplant recipient having post-transplant lymphoproliferative disorders. Pediatr Transplant 2006;10:377–9. 6. Favero M, Raffeiner B, Cecchin D et al. Septic arthritis caused by Rothia dentocariosa in a patient with rheumatoid arthritis receiving etanercept therapy. J Rheumatol 2009;36:2846–7. 7. Rutgeerts P, Sandborn WJ, Feagan BG et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462–76. 1
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 2 Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Correspondence: Baljinder Salh, MD, Division of Gastroenterology, Department of Medicine, Gordon & Leslie Diamond Health Care Ctr., 5th Floor, 2775 Laurel Street, Vancouver, British Columbia, Canada V5Z 1M9. E-mail: [email protected]
ing in the background of high-grade dysplasia at the gastroesophageal junction. He was treated with a combination of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) and achieved complete eradication of intestinal metaplasia. Surveillance biopsies obtained a year following his last RFA treatment showed moderately differentiated IMC identified under squamous epithelium (SE) at a site close in location to his previous cancer. This was not seen on a high-resolution white light endoscopy and was only detected on mapping biopsies. A subsequent EMR was performed over an area of normal-appearing mucosa corresponding to the prior biopsy site. Histopathology demonstrated moderate to poorly differentiated IMC invading into the lamina propria and muscularis mucosa with negative mucosal and submucosal margins for cancer (Figure 1). Endoscopic ultrasound did not show evidence of esophageal wall thickening or regional lymphadenopathy. Imaging with confocal laser endomicroscopy (CLE) and volumetric laser endomicroscopy (VLE) was performed on the EMR specimen immediately following resection to ensure visualization of identical areas. Surface imaging with CLE using the fluorescent glucose analog 2-NBDG showed
a homogenous layer of SE (1). Cross-sectional imaging with VLE demonstrated BE with features suggestive of IMC, including increased signal intensity (black arrow) with numerous atypical-appearing glands and dilated ducts (white arrows) underneath a layer of SE (Figure 2). Subsquamous BE is found in ~0.9% of surveillance biopsies following RFA (2). Most of the time, subsquamous BE is nondysplastic but cancer has clearly been found in multiple series and presents a challenging diagnosis (3). VLE is a second-generation optical coherence tomography device that can generate in-vivo three-dimensional views of the human esophagus (4). Advantages of VLE over CLE are the capacity to perform wide-field imaging and the ability to visualize deeper into the mucosa (Supplementary Figures S1–S3 online). After ablative therapy for BE, it is essential to perform careful mapping biopsies of the mucosa to detect these small areas of residual cancer. This is the first case reported where VLE could clearly detect subsquamous Barrett’s adenocarcinoma, which was not seen by routine white light endoscopy or CLE. The use of in-vivo VLE has the potential to enhance the diagnosis of subsquamous BE and associated neoplasia.
Volumetric Laser Endomicroscopy Detects Subsquamous Barrett’s Adenocarcinoma Cadman L. Leggett, MD1, Emmanuel Gorospe, MD1, Victoria L. Owens, MD2, Marlys Anderson, BS1, Lori Lutzke, CCRP1 and Kenneth K. Wang, MD1
1 mm
Figure 1. Endoscopic mucosal resection showing subsquamous moderate to poorly differentiated adenocarcinoma invading into the lamina propria and muscularis mucosa.
SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg
doi: 10.1038/ajg.2013.422
SE IMC
To the Editor: A 74-year-old patient with Barrett’s esophagus (BE) (C5M5) enrolled in a surveillance program was found to have intramucosal adenocarcinoma (IMC) arisThe American Journal of GASTROENTEROLOGY
1 mm
Figure 2. Volumetric laser endomicroscopy of endoscopic mucosal resection with features suggestive of intramucosal adenocarcinoma (IMC), including increased signal intensity (black arrow) with atypical appearing glands and dilated ducts (white arrows) underneath a layer of squamous epithelium (SE).
VOLUME 109 | FEBRUARY 2014 www.amjgastro.com
