Digestive Endoscopy 2014; ••: ••–••
doi: 10.1111/den.12317
Case Report
Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection Tsukasa Ishida,1 Yoshinori Morita,1 Namiko Hoshi,1 Tetsuya Yoshizaki,1 Yoshiko Ohara,1 Fumiaki Kawara,1 Sinwa Tanaka,3 Yuki Yamamoto,2 Hiroo Matsuo,2 Kentaro Iwata,2 Takashi Toyonaga3 and Takeshi Azuma1 1
Division of Gastroenterology, 2Division of Infectious Diseases, Department of Internal Medicine, Graduate School of Medicine, and 3Department of Endoscopy, Kobe University, Kobe, Japan
An 85-year-old man underwent endoscopic submucosal dissection for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were given orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography revealed a nodular lesion in the lung. Sputum sample showed Gram-positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging revealed multiple focal lesions
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) can resect large superficial neoplasms en bloc. However, it is known that mucosal resection of more than threequarters of the circumference of the esophagus can cause esophageal stricture. Therefore, prophylactic countermeasures against this should be taken.1 One strategy is endoscopic balloon dilation (EBD); however, a high risk of perforation during EBD has previously been reported.2 Another option is the use of steroids, which can be given by intralesional injection or systemically. Intralesional steroid injection, sometimes with EBD, has been widely used; however, there are cases that are refractory to this treatment.3 To resolve these problems, systemic administration has been used, and favorable results have been reported without critical adverse events.4 Here, we present a case of disseminated
bs_bs_banner
Corresponding: Tsukasa Ishida, Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo 6500017, Japan. Email: [email protected] Received 31 March 2014; accepted 22 May 2014.
which indicated dissemination of nocardiosis. Trimethoprimsulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, the present case indicates the risk of life-threatening infection and the importance of close monitoring of this treatment. Key words: endoscopic submucosal dissection (ESD), esophageal stricture, Nocardia, nocardiosis, steroid
nocardiosis during the course of systemic steroid therapy against esophageal stricture after ESD.
CASE REPORT
A
N 85-YEAR-OLD MAN was admitted to Kobe University Hospital for endoscopic treatment to remove a large superficial neoplasm extending from the mid- to the lower thoracic esophagus. He underwent ESD that required removal of 95% of the circumference of the esophageal mucosa (Fig. 1). Pathological examination of the resected specimen showed moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosa, without lymphatic and vascular invasion. He did not have any complications during the procedure, but the development of esophageal stricture was predicted. He was negative for hepatitis virus infection, as confirmed by a serological test. There was no evidence of lung tuberculosis and nodular lesion by chest computed tomography (CT) scan. Therefore, systemic prednisolone was started to prevent the development of esophageal stricture. The regimen involved giving 30 mg daily oral prednisolone from the third day post-ESD that was gradually tapered until discontinuation at 8 weeks.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
T. Ishida et al.
Digestive Endoscopy 2014; ••: ••–••
A
B
C
D
A
B
Figure 1 Superficial esophageal carcinoma involves almost the whole circumference of the esophagus. (A) White light view. (B) Iodine stain view. (C) Artificial ulcer after removal of the lesion. (D) Specimen resected en bloc.
Figure 2 (A) Chest computed tomography (CT) scan before endoscopic submucosal dissection (ESD) demonstrates mild emphysema and a few nonspecific pneumonia lesions at the lower lung field. (B) Chest CT scan 6 weeks after ESD demonstrates a nodular lesion of approximately 25 mm in the right lower lung field.
He had no complications and prednisolone was tapered to 10 mg/day before he presented at the emergency department with a high fever of 38°C 6 weeks after the indication of steroids. Laboratory tests revealed increases in the white blood cell count (11 900/μL) and C-reactive protein (5.73 mg/dL). He underwent chest CT scan to check for any abnormal findings, particularly around the esophagus. This revealed a small nodular lesion in the right lower lung field (Fig. 2) that had not been found in the CT scan taken before ESD. A sputum sample was tested by Gram staining and Gram-positive, thin, branching filamentous bacteria were detected. From these findings, Nocardia infection was suspected (Fig. 3). Nocar-
diosis preferentially spreads to the brain, so contrastenhanced brain magnetic resonance imaging (MRI) was carried out. It revealed some small brain abscesses (Fig. 4). We further carried out 16S rRNA sequencing, and identified the case as Nocardia farcinica infection. Antibiotic susceptibility test showed that it was sensitive to trimethoprimsulfamethoxazole (TMP-SMX). The fever was immediately alleviated after giving TMP-SMX, and the complete disappearance of pulmonary consolidation and brain abscess was confirmed 6 months after treatment. The patient continued to take TMP-SMX for 1 year and there was no sign of recurrence of Nocardia infection. As for the esophageal stricture, it occurred 9 weeks after ESD. Subsequently, we carried out
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Disseminated nocardiosis after ESD 3
Figure 3 Sputum smear was recognized as Nocardia spp. Gram stain demonstrates Gram-positive, thin, branching, filamentous forms.
EBD therapy once a week. However, when we carried out the second EBD at 15 mm, minimal esophageal perforation occurred. Fortunately, this perforation improved upon a few days of fasting. Then, the EBD was continued from a week later for a total of 13 times, which spanned 3 months. The stricture was improved to the extent that passage of an endoscope could easily occur.
DISCUSSION
R
ECENTLY, IT HAS been shown that the frequency of complications such as perforation during endoscopic therapy for superficial esophageal carcinoma is decreasing, presumably as a result of the improvement of devices and therapeutic techniques.5
A
However, complications during management of the postoperative state are another problem to overcome. Esophageal stricture is a major complication after resection of more than three-quarters of the circumference of an esophageal tumor.1 It can cause dysphagia and a decreased quality of life, and may increase the risk of aspiration pneumonia.6 Preventive EBD is one of the strategies to treat dysphasia caused by esophageal stricture;7 however, in cases of nearly complete circumferential mucosal removal, repetitive EBD is sometimes required every week for more than 2 to 3 months. This can lead to an increased risk of perforation by EBD. Systemic steroid therapy is reportedly effective to prevent postoperative esophageal stricture without serious complications;4 therefore, it is expected to be an alternative or a complementary therapy for EBD. However, one should always be aware that the immunosuppressive effect of steroids can expose the patient to a life-threatening infection. Nocardia is found in soil worldwide and is generally acquired via inhalation.8 Nocardia spp. are known as opportunistic pathogens with low virulence, so they usually only affect immune-compromised individuals. Following colonization of Nocardia spp. in the respiratory tract, T-lymphocyte-mediated cellular immunity is activated after phagocytosis of the organism by innate cells such as macrophages.8 In general, corticosteroid treatment inhibits the cytokine response and phagocytic killing of microbes by macrophages, and triggers dissemination of the pathogen from local to systemic organs.9 Previous reports indicated that most nocardiosis patients (61.2%) were undergoing systemic steroid treatment or chemotherapy.8 Nocardia spp. spread easily hematogenously to extrapulmonary organs, and 2–20% of nocardiosis cases involve cerebral abscesses. Disseminated nocardiosis shows a poor prognosis with a
B
Figure 4 Brain magnetic resonance imaging with gadolinium-DTPA. (A) T1weighted image showing multiple ringenhanced masses in the bilateral cerebral hemispheres. (B) T2-weighted image showing marked perifocal edema.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
4
T. Ishida et al.
mortality rate of 30–80%, and the major cause of death is cerebral infection.8 The patient in the present case had no remarkable medical history. He previously smoked 20 cigarettes every day for 50 years; however, he had quit smoking and had been smoke free for over 16 years. This indicates that, other than his age, there was no indication for an immunocompromised state or a predisposition to opportunistic infections before the steroid was given. However, in retrospect, there were mild emphysema and a few non-specific pneumonia lesions at the lower lung field by chest CT scan. Of note, the patient’s hobby was gardening, which may have exposed him to frequent contact with Nocardia spp. Therefore, it was possible that he had subclinical nocardia in the lung, which disseminated as a result of the steroid treatment. Our case suggests the necessity of prophylaxis therapy to prevent life-threatening infections in patients undergoing systemic steroid treatment for postoperative esophageal stricture. This is relevant because the present patient took a total of 1120 mg prednisolone, and it is known that patients taking more than a total amount of 700 mg prednisolone or undergoing a period of systemic steroid administration of 21 days have an increased risk of susceptibility to infection.9 TMP-SMX prophylaxis is effective against opportunistic pathogens such as Nocardia and Pneumocystis jirovecii.10 However, it has been shown that 10.4% of patients receiving TMP-SMX prophylaxis were infected by Nocardia.8 As there is no perfect medication to avoid opportunistic infection, sufficient effort should be made for early detection of any sign of infection in patients undergoing systemic steroid treatment, as previously mentioned. In the present case, esophageal stricture could not be prevented by 8-week oral steroid treatment. This suggests that longer-term steroid treatment may be needed for prevention. However, such therapy is associated with a high risk in the elderly, in those with uncontrolled diabetes, and in those with previous infections. Therefore, we consider it necessary to reduce the amount of oral steroid given and shorten the duration of systemic steroid therapy, for example, by using a combination with intraluminal steroid injection or new therapeutic strategies.
CONCLUSION
T
HE PRESENT CASE involved a life-threatening complication of esophageal ESD. It is important to be
Digestive Endoscopy 2014; ••: ••–••
careful of infections, including disseminated nocardiosis, during systemic steroid treatment for the prevention of esophageal stricture.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Mizuta H, Nishimori I, Kuratani Y et al. Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer. Dis. Esophagus 2009; 22: 626– 31. 2 Takahashi H, Arimura Y, Okahara S et al. Risk of perforation during dilation for esophageal strictures after endoscopic resection in patients with early squamous cell carcinoma. Endoscopy 2011; 43: 184–9. 3 Hanaoka N, Ishihara R, Takeuchi Y. Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: A controlled prospective study. Endoscopy 2012; 44: 1007–11. 4 Yamaguchi N, Isomoto H, Nakayama T et al. Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Gastrointest. Endosc. 2011; 73: 1115–21. 5 Shimizu Y, Takahashi M, Yoshida T et al. Endoscopic resection (endoscopic mucosal resection/endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: Current status of various techniques. Dig. Endosc. 2013; 25 (Suppl 1): 13–9. 6 Fujishiro M. Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms. World J. Gastroenterol. 2008; 21: 4289–95. 7 Ezoe Y, Muto M, Horimatsu T et al. Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection. J. Clin. Gastroenterol. 2011; 45: 222–7. 8 Budzik JM, Hosseini M, Mackinnon AC Jr et al. Disseminated Nocardia farcinica: Literature review and fatal outcome in an immunocompetent patient. Surg. Infect. 2012; 13: 163–70. 9 Klein NC, Go CH, Cunha BA. Infections associated with steroid use. Infect. Dis. Clin. North Am. 2001; 15: 423–32. 10 Cockerill FR, Edson RS. Trimethoprim-sulfamethoxazole. Mayo Clin. Proc. 1991; 66: 1260–9.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
doi: 10.1111/den.12317
Case Report
Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection Tsukasa Ishida,1 Yoshinori Morita,1 Namiko Hoshi,1 Tetsuya Yoshizaki,1 Yoshiko Ohara,1 Fumiaki Kawara,1 Sinwa Tanaka,3 Yuki Yamamoto,2 Hiroo Matsuo,2 Kentaro Iwata,2 Takashi Toyonaga3 and Takeshi Azuma1 1
Division of Gastroenterology, 2Division of Infectious Diseases, Department of Internal Medicine, Graduate School of Medicine, and 3Department of Endoscopy, Kobe University, Kobe, Japan
An 85-year-old man underwent endoscopic submucosal dissection for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were given orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography revealed a nodular lesion in the lung. Sputum sample showed Gram-positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging revealed multiple focal lesions
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) can resect large superficial neoplasms en bloc. However, it is known that mucosal resection of more than threequarters of the circumference of the esophagus can cause esophageal stricture. Therefore, prophylactic countermeasures against this should be taken.1 One strategy is endoscopic balloon dilation (EBD); however, a high risk of perforation during EBD has previously been reported.2 Another option is the use of steroids, which can be given by intralesional injection or systemically. Intralesional steroid injection, sometimes with EBD, has been widely used; however, there are cases that are refractory to this treatment.3 To resolve these problems, systemic administration has been used, and favorable results have been reported without critical adverse events.4 Here, we present a case of disseminated
bs_bs_banner
Corresponding: Tsukasa Ishida, Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo 6500017, Japan. Email: [email protected] Received 31 March 2014; accepted 22 May 2014.
which indicated dissemination of nocardiosis. Trimethoprimsulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, the present case indicates the risk of life-threatening infection and the importance of close monitoring of this treatment. Key words: endoscopic submucosal dissection (ESD), esophageal stricture, Nocardia, nocardiosis, steroid
nocardiosis during the course of systemic steroid therapy against esophageal stricture after ESD.
CASE REPORT
A
N 85-YEAR-OLD MAN was admitted to Kobe University Hospital for endoscopic treatment to remove a large superficial neoplasm extending from the mid- to the lower thoracic esophagus. He underwent ESD that required removal of 95% of the circumference of the esophageal mucosa (Fig. 1). Pathological examination of the resected specimen showed moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosa, without lymphatic and vascular invasion. He did not have any complications during the procedure, but the development of esophageal stricture was predicted. He was negative for hepatitis virus infection, as confirmed by a serological test. There was no evidence of lung tuberculosis and nodular lesion by chest computed tomography (CT) scan. Therefore, systemic prednisolone was started to prevent the development of esophageal stricture. The regimen involved giving 30 mg daily oral prednisolone from the third day post-ESD that was gradually tapered until discontinuation at 8 weeks.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
T. Ishida et al.
Digestive Endoscopy 2014; ••: ••–••
A
B
C
D
A
B
Figure 1 Superficial esophageal carcinoma involves almost the whole circumference of the esophagus. (A) White light view. (B) Iodine stain view. (C) Artificial ulcer after removal of the lesion. (D) Specimen resected en bloc.
Figure 2 (A) Chest computed tomography (CT) scan before endoscopic submucosal dissection (ESD) demonstrates mild emphysema and a few nonspecific pneumonia lesions at the lower lung field. (B) Chest CT scan 6 weeks after ESD demonstrates a nodular lesion of approximately 25 mm in the right lower lung field.
He had no complications and prednisolone was tapered to 10 mg/day before he presented at the emergency department with a high fever of 38°C 6 weeks after the indication of steroids. Laboratory tests revealed increases in the white blood cell count (11 900/μL) and C-reactive protein (5.73 mg/dL). He underwent chest CT scan to check for any abnormal findings, particularly around the esophagus. This revealed a small nodular lesion in the right lower lung field (Fig. 2) that had not been found in the CT scan taken before ESD. A sputum sample was tested by Gram staining and Gram-positive, thin, branching filamentous bacteria were detected. From these findings, Nocardia infection was suspected (Fig. 3). Nocar-
diosis preferentially spreads to the brain, so contrastenhanced brain magnetic resonance imaging (MRI) was carried out. It revealed some small brain abscesses (Fig. 4). We further carried out 16S rRNA sequencing, and identified the case as Nocardia farcinica infection. Antibiotic susceptibility test showed that it was sensitive to trimethoprimsulfamethoxazole (TMP-SMX). The fever was immediately alleviated after giving TMP-SMX, and the complete disappearance of pulmonary consolidation and brain abscess was confirmed 6 months after treatment. The patient continued to take TMP-SMX for 1 year and there was no sign of recurrence of Nocardia infection. As for the esophageal stricture, it occurred 9 weeks after ESD. Subsequently, we carried out
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Disseminated nocardiosis after ESD 3
Figure 3 Sputum smear was recognized as Nocardia spp. Gram stain demonstrates Gram-positive, thin, branching, filamentous forms.
EBD therapy once a week. However, when we carried out the second EBD at 15 mm, minimal esophageal perforation occurred. Fortunately, this perforation improved upon a few days of fasting. Then, the EBD was continued from a week later for a total of 13 times, which spanned 3 months. The stricture was improved to the extent that passage of an endoscope could easily occur.
DISCUSSION
R
ECENTLY, IT HAS been shown that the frequency of complications such as perforation during endoscopic therapy for superficial esophageal carcinoma is decreasing, presumably as a result of the improvement of devices and therapeutic techniques.5
A
However, complications during management of the postoperative state are another problem to overcome. Esophageal stricture is a major complication after resection of more than three-quarters of the circumference of an esophageal tumor.1 It can cause dysphagia and a decreased quality of life, and may increase the risk of aspiration pneumonia.6 Preventive EBD is one of the strategies to treat dysphasia caused by esophageal stricture;7 however, in cases of nearly complete circumferential mucosal removal, repetitive EBD is sometimes required every week for more than 2 to 3 months. This can lead to an increased risk of perforation by EBD. Systemic steroid therapy is reportedly effective to prevent postoperative esophageal stricture without serious complications;4 therefore, it is expected to be an alternative or a complementary therapy for EBD. However, one should always be aware that the immunosuppressive effect of steroids can expose the patient to a life-threatening infection. Nocardia is found in soil worldwide and is generally acquired via inhalation.8 Nocardia spp. are known as opportunistic pathogens with low virulence, so they usually only affect immune-compromised individuals. Following colonization of Nocardia spp. in the respiratory tract, T-lymphocyte-mediated cellular immunity is activated after phagocytosis of the organism by innate cells such as macrophages.8 In general, corticosteroid treatment inhibits the cytokine response and phagocytic killing of microbes by macrophages, and triggers dissemination of the pathogen from local to systemic organs.9 Previous reports indicated that most nocardiosis patients (61.2%) were undergoing systemic steroid treatment or chemotherapy.8 Nocardia spp. spread easily hematogenously to extrapulmonary organs, and 2–20% of nocardiosis cases involve cerebral abscesses. Disseminated nocardiosis shows a poor prognosis with a
B
Figure 4 Brain magnetic resonance imaging with gadolinium-DTPA. (A) T1weighted image showing multiple ringenhanced masses in the bilateral cerebral hemispheres. (B) T2-weighted image showing marked perifocal edema.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
4
T. Ishida et al.
mortality rate of 30–80%, and the major cause of death is cerebral infection.8 The patient in the present case had no remarkable medical history. He previously smoked 20 cigarettes every day for 50 years; however, he had quit smoking and had been smoke free for over 16 years. This indicates that, other than his age, there was no indication for an immunocompromised state or a predisposition to opportunistic infections before the steroid was given. However, in retrospect, there were mild emphysema and a few non-specific pneumonia lesions at the lower lung field by chest CT scan. Of note, the patient’s hobby was gardening, which may have exposed him to frequent contact with Nocardia spp. Therefore, it was possible that he had subclinical nocardia in the lung, which disseminated as a result of the steroid treatment. Our case suggests the necessity of prophylaxis therapy to prevent life-threatening infections in patients undergoing systemic steroid treatment for postoperative esophageal stricture. This is relevant because the present patient took a total of 1120 mg prednisolone, and it is known that patients taking more than a total amount of 700 mg prednisolone or undergoing a period of systemic steroid administration of 21 days have an increased risk of susceptibility to infection.9 TMP-SMX prophylaxis is effective against opportunistic pathogens such as Nocardia and Pneumocystis jirovecii.10 However, it has been shown that 10.4% of patients receiving TMP-SMX prophylaxis were infected by Nocardia.8 As there is no perfect medication to avoid opportunistic infection, sufficient effort should be made for early detection of any sign of infection in patients undergoing systemic steroid treatment, as previously mentioned. In the present case, esophageal stricture could not be prevented by 8-week oral steroid treatment. This suggests that longer-term steroid treatment may be needed for prevention. However, such therapy is associated with a high risk in the elderly, in those with uncontrolled diabetes, and in those with previous infections. Therefore, we consider it necessary to reduce the amount of oral steroid given and shorten the duration of systemic steroid therapy, for example, by using a combination with intraluminal steroid injection or new therapeutic strategies.
CONCLUSION
T
HE PRESENT CASE involved a life-threatening complication of esophageal ESD. It is important to be
Digestive Endoscopy 2014; ••: ••–••
careful of infections, including disseminated nocardiosis, during systemic steroid treatment for the prevention of esophageal stricture.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Mizuta H, Nishimori I, Kuratani Y et al. Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer. Dis. Esophagus 2009; 22: 626– 31. 2 Takahashi H, Arimura Y, Okahara S et al. Risk of perforation during dilation for esophageal strictures after endoscopic resection in patients with early squamous cell carcinoma. Endoscopy 2011; 43: 184–9. 3 Hanaoka N, Ishihara R, Takeuchi Y. Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: A controlled prospective study. Endoscopy 2012; 44: 1007–11. 4 Yamaguchi N, Isomoto H, Nakayama T et al. Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Gastrointest. Endosc. 2011; 73: 1115–21. 5 Shimizu Y, Takahashi M, Yoshida T et al. Endoscopic resection (endoscopic mucosal resection/endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: Current status of various techniques. Dig. Endosc. 2013; 25 (Suppl 1): 13–9. 6 Fujishiro M. Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms. World J. Gastroenterol. 2008; 21: 4289–95. 7 Ezoe Y, Muto M, Horimatsu T et al. Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection. J. Clin. Gastroenterol. 2011; 45: 222–7. 8 Budzik JM, Hosseini M, Mackinnon AC Jr et al. Disseminated Nocardia farcinica: Literature review and fatal outcome in an immunocompetent patient. Surg. Infect. 2012; 13: 163–70. 9 Klein NC, Go CH, Cunha BA. Infections associated with steroid use. Infect. Dis. Clin. North Am. 2001; 15: 423–32. 10 Cockerill FR, Edson RS. Trimethoprim-sulfamethoxazole. Mayo Clin. Proc. 1991; 66: 1260–9.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
