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Implications of Clostridium septicum in Vascular Surgery: A Case Report and Outcomes Literature Review
Case Report Implications of Clostridium septicum in Vascular Surgery: A Case Report and Outcomes Literature Review Yewande Alimi,1 Michael Sosin,1 Tracy M. Borsinger,2 John R. Garrett,3 J.R. Salameh,3 and C. Francisco Espinel,3 Washington, DC, and Arlington, Virginia
Clostridium septicum is a rare organism, accounting for approximately 1.3% of clostridial infections and is associated with synchronous colonic malignancy. This case report describes a patient successfully treated for a mycotic aortic aneurysm secondary to C. septicum bacteremia. Subsequent evaluation confirmed a colonic malignancy, prompting early intervention. A systematic literature review revealing a rate of gastrointestinal malignancy in this patient population is 71%, and hematologic malignancy is 3.9%, with the remaining cohort of patients having an unknown source. Infectious involvement of the aorta and associated vascular structures portends a poor prognosis with a 57% mortality rate. Our case and updated review demonstrates the implications of C. septicum vascular seeding and subsequent treatment outcomes.
Clostridium septicum is a very rare gram-positive spore-forming motile bacillus1 associated with colonic malignancy and has a propensity for aortic seeding. A heightened awareness of the increased risk of concomitant colonic malignancy and aortic involvement should prompt early diagnostic imaging. Although few cases have been reported in the literature, there is mounting evidence that early initiation of targeted antibiotic therapy and surgical intervention decreases morbidity and mortality. This case report describes the surgical and medical
Conflict of interest: The authors declare no conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 1 Department of Surgery, Medstar Georgetown University Hospital, Washington, DC. 2 Georgetown University School of Medicine, Washington, DC. 3
Virginia Hospital Center, Arlington, VA.
Correspondence to: C. Francisco Espinel, MD, Virginia Hospital Center 1625 N. George Mason Drive, Suite 334, Arlington, VA 22205, USA; E-mail: [email protected] Ann Vasc Surg 2017; -: 1–7 http://dx.doi.org/10.1016/j.avsg.2017.03.178 Ó 2017 Elsevier Inc. All rights reserved. Manuscript received: January 29, 2017; manuscript accepted: March 28, 2017; published online: - - -
management of a 66-year-old male with C. septicum bacteremia with a mycotic aneurysm and a synchronous colonic malignancy. In addition, a systematic literature review was completed to assess concurrent neoplasms associated with C. septicum vascular seeding to define the outcomes in this cohort of patients.
CASE REPORT A 66-year-old, otherwise healthy male, presented with a 48-hour duration of increasing, diffuse abdominal pain radiating to his back with associated subjective fever and chills. The patient had not sought medical care in over 15 years, but a visit to an urgent care clinic following the onset of symptoms was suspected to be muscular pain in origin. Days prior, he was treated with a muscle relaxant and opioid pain medication without resolution. On evaluation, the patient was febrile to 101.3 F, and a computed tomography scan revealed a mycotic aneurysm of the infrarenal aorta with evidence of necrotizing aortitis (Fig. 1). No bowel abnormalities or masses were observed. Blood cultures were obtained, and broad-spectrum intravenous antibiotic therapy (vancomycin and piperacillin/ tazobactam) was initiated. The patient remained hemodynamically stable and was immediately taken to the operating room. Surgical 1
2 Case Report
Fig. 1. A coronal (A) and transverse view (B) of the computed tomography scan showing a fusiform aneurysmal dilatation of the infrarenal abdominal aorta
intervention consisted of excision of the infrarenal abdominal aortic aneurysm with a right axillofemoral bypass using a Gore-Tex (Gore Medical Products, Flagstaff, AZ) graft, and a right-to-left femoral-femoral (end-to-side) bypass using the same prosthetic material. The patient recovered without complication, and intraoperative blood cultures revealed growth of C. septicum. The association of this rare organism with a concurrent colonic neoplasm prompted a colonoscopy during the same hospital stay. Colonoscopy revealed an ascending colon mass, which was biopsied with pathology demonstrating severe glandular dysplasia with atypical cytologic features, without definitive invasion. Following convalescence from the aforementioned surgery and discharge, the patient remained on intravenous ertapenem daily for 6 weeks, with ultimate resolution of bacteremia. Four weeks later, the patient returned to the operating room for a laparoscopic right hemicolectomy and recovered without complication. The lesion measured 7.5 4.5 4 cm with moderately differentiated invasive adenocarcinoma (pT3pN0pM0). Upon 20-month follow-up, the patient was without recurrence.
DISCUSSION C. septicum is not a typical organism of the gut flora, and the specific entity remains incredibly rare accounting for approximately 1% of all clostridium infections. Seder et al.2 have described the association of C. septicum infections and the development of aortitis, aneurysm, and aortic dissection. However, the C. septicumeassociated literature has expanded since that review. We performed a systematic literature review as outlined in Figure 2 to identify the published cases of C. septicum with vascular seeding. To date, including our patient, 51 cases of C. septicum aortitis have been documented (Table I), and 71% (n ¼ 36) are associated with a concurrent gastrointestinal malignancy or premalignant lesion. It is
Annals of Vascular Surgery
measuring 4.4 4.7 cm (arrow) in greatest dimension. Foci of gas along the intima of the aorta are depicted with arrowheads.
Fig. 2. Flowchart depicting the systematic selection process for inclusion and exclusion of articles in the review. The MEDLINE (via PubMed) and EMBASE databases were queried using controlled vocabulary terms where appropriate (Medical Subject Heading and Emtree terms) in combination with relevant keywords and phrases. The search strategy focused on Clostridium septicum, colonic neoplasms, malignancies, aortitis, and aneurysm in combination with the Boolean operators AND or OR for articles published up until May 15, 2016. A total of 145 articles were obtained from this search after duplications were removed. Of these articles, 93 articles were excluded on the basis of lack of including vascular pathology. A full-text review of 52 articles was completed.
believed that the pH, electrolyte, and osmotic composition of the cecum provide an environment that is ideal for the growth of C. septicum.2 The postulated mechanism of infection involves colonic
Table I. Cases of Clostridium septicum with vascular involvement Year
Bridges et al.3
Age
Process
Location
Neoplasm
Surgery
1981 68
M
No
Aneurysm
Infrarenal
Unknown
ABF, omental patch
Semel et al.4
1984 60
F
No
Aneurysm
Ascending/arch
Kaufman et al.5
1988 62
M
Narula et al.6
1988 76
M
Unknown Dissection/ aneurysm No Aneurysm
Popliteal
Transverse colon adenocarcinoma Waldenstrom macroglobulinemia Colon adenocarcinoma
Momont and Overholt7 Asplund and Molinaro8
1989 85
F
No
1990 80
Brahan and Kahler9
Iliac and femoral
Alive, duration unknown Partial colectomy Died, 20 hours postoperatively None Died 6 hours after admission Ligation and excision of Alive, duration aneurysm, right unknown hemicolectomy None Died
Cecal adenocarcinoma
Iliac
Cecal carcinoma
1990 70
F
Yes
Aneurysm
Arch/descending
Ascending colon adenocarcinoma
Hurley and Howe10
1991 67
M
Yes
Aneurysm
Infrarenal
Rectal, colonic adenomas
Christensen and Bistrup11 de Gara and Mandel12 Messa et al.13
1993 74
F
Yes
Aneurysm
Juxtarenal
None
Aneurysm excision, extraanatomic femoral-femoral bypass, right hemicolectomy In situ graft, resection of PA to aneurysm fistula Right ABF, aneurysm resection, left ABF for infected graft None
1994 56
M
No
Aneurysm
Infrarenal
Crohn’s disease
Aneurysm repair
1995 77
M
Yes
Double aneurysm
Sigmoid adenocarcinoma
Upchurch et al.14
1995 67
M
Yes
Graft
Descending thoracic/ juxtarenal Abdominal
Murphy et al.15
1996 78
M
No
Aneurysm
In situ thoracic graft with omental flap and ABF ABF and removal of graft, right hemicolectomy, In situ graft and esophagectomy
Sailors et al.16 Monsen et al.17
1996 74 1997 81
F M
No No
Aneurysm Dissection
Montoya et al.18
1997 78
M
Unknown Aneurysm
Proximal descending thoracic Thoracoabdominal Ascending to infrarenal Descending thoracic
Benign sigmoid polyps
None Cecal adenocarcinoma
In situ graft In situ
Cecal adenocarcinoma
None
Died, 10 months postoperatively
Alive at 36 months
Alive at 9 months
Died Alive, unknown duration Alive at 4 months
Alive at 3 years
Alive at 6 months
Died, 3.5 months later Died 5 hours postoperatively Died, 16 hours after admission (Continued)
Case Report 3
Ascending/arch
M
Dissection/ aneurysm Unknown Aneurysm
Ascending colon adenocarcinoma
Outcome
2017
Diabetic
-, -
Sex
Volume
Author
Author
Year
Cohen et al.19 Johnson20 Morrison et al.21
Age
Diabetic
Process
1998 77
M
1999 78 2001 71
M M
Unknown Dissection/ abscess Yes Aneurysm No Aneurysm
Al Bahrani et al.22 2001 63
M
Unknown Aneurysm
Munshi et al.23 Zenati et al.24
2002 78 2002 87
M M
Liechti et al.25
2003 55
M
No Aneurysm Unknown Dissection/ aneurysm No Aneurysm
Takano et al.26
2003 69
M
Unknown Aneurysm
Davies et al.27
2003 63
M
No
Aneurysm
Infrarenal
Unknown
Rucker et al.28
2004 77
F
No
Aneurysm
Infrarenal
Cecal adenocarcinoma
Rucker et al.28
2004 91
F
No
Aortitis
Evans and Chey29
2004 91
F
Unknown Aortitis
SMA to iliac arteries Abdominal
Mohamed et al.30
2006 82
M
No
Juxtarenal
Asciutto et al.31
2007 71
M
Unknown Aortitis
Juxtarenal
Ascending adenocarcinoma Transverse colon adenocarcinoma Ascending adenocarcinoma Ascending colon adenocarcinoma
Laudito et al.32
2008 74
F
Yes
Arch/ascending
Seder et al.2
2008 75
M
Seder et al.2
2008 76
Gai et al.33
Aneurysm
Location
Neoplasm
Aortic root/ Cecal adenocarcinoma ascending Infrarenal Unknown Thoracoabdominal Ascending colon adenocarcinoma Infrarenal Ascending colon adenocarcinoma Infrarenal Cecal adenoma Innominate Cecal adenocarcinoma to renal arteries Infrarenal Transverse colon adenocarcinoma Infrarenal Ascending colon adenocarcinoma
Surgery
Outcome
Right hemicolectomy
Died, hospital day 33
None In situ
Died, hospital day 6 Alive at 36 months
Unspecified reconstruction None None
Alive, unknown duration Died, 1 month later Died, on hospital day 6
Exploration of aorta, transverse colectomy In situ with omental flap revised to a rectus abdominus flap, right hemicolectomy ABF
Died, 5 month later
ABF, right hemicolectomy Right colectomy Extended right hemicolectomy In situ graft, right hemicolectomy In situ graft and wide tissue debridement, right hemicolectomy ABF, hemicolectomy
No
Aortitis/ dissection Aneurysm
Infrarenal
F
No
Aneurysm
Juxtarenal
Adenocarcinoma descending colon Ascending adenocarcinoma Cecal adenocarcinoma
2009 76
F
Yes
Arch/descending
Colon adenocarcinoma
ABF, right hemicolectomy ABF, right hemicolectomy ABF, hemicolectomy
Yang and Reilly34
2009 22
M
Entire aorta
None
None
Dulaney et al.35
2010 74
M
Ascending aorta
Plasma cell myeloma, rectal adenocarcinoma
None
Aortitis/ dissection No Aortitis/ dissection Unknown Dissection/ abscess
Alive at 60 months
Died, 2 days postoperatively Died, 42 days postoperatively Unknown Died, 5 months later Alive at 15 months Alive, unknown duration Alive, unknown duration Died, 4 months later Died, 3 months later Alive, unknown duration Died, 8 hours after presentation Died, hospital day 7
Annals of Vascular Surgery
Sex
4 Case Report
Table I. Continued
Yes
Colwick et al.37
2011 82
M
Unknown Aneurysm
Granier et al.38
2011 83
M
Unknown Aortitis
Mao et al.39
2011 73
M
Unknown Aortitis
Annapureddy et al.40 Demidovich et al.41 Phillip and de Virgilio42 Khalid et al.43
2012 69
M
No
2012 69
F
2012 87
M
Aortitis with Infrarenal aneurysm Unknown Aneurysm Descending thoracic Yes Aortitis Juxtarenal
2012 77
M
Unknown Aneurysm
Infrarenal
Mbianda et al.44 Present case report
2012 73 2013 66
M M
Unknown Aortitis No Aneurysm
Arch Infrarenal
Cecal adenocarcinoma Ascending colon adenocarcinoma
Tokmaji et al.45
2013 71
M
Unknown Aneurysm
Abdominal
None
Al Hadi et al.46
2014 63
M
Unknown Aneurysm
Eplinius and Hadrich47
2014 32
M
No
Dissection
Hashimoto et al.48
2014 81
M
No
Aneurysm
Lintin et al.49
2014 78
F
Unknown Aneurysm
Arch/ descending Ascending/ descending thoracic Arch/ descending Thoracic aorta
Aortitis Juxtarenal, previous graft Descending thoracic Unknown
Right hemicolectomy
Died, 75 days after admission ABF with graft, omental Alive, unknown patch duration None Died, hospital day 3
Cecal adenocarcinoma
None
None
ABF with graft, none
Died, during hospitalization Alive at 6 months
Unspecified colonic mass Sigmoid adenocarcinoma Multifocal colonic adenocarcinoma
None
Died before surgery
None
Died, 5 weeks later Alive, unknown duration
Ascending colon adenocarcinoma None
Resection of aneurysm with graft, right hemicolectomy Resection aortic arch ABF, femoral-femoral bypass, excision of aneurysm, right hemicolectomy ABF with femoralfemoral bypass None, right hemicolectomy None
Unknown
None
Died, hospital day 6
ICV colon adenocarcinoma, liver metastasis
Right-to-left common carotid crossover bypass, left common carotid to left subclavian bypass (double transposition), right hemicolectomy
Alive at 28 months
Died postoperatively Alive at 20 months
Alive at 2 months Died, hospital day 3 Died, 6 days after presentation
Case Report 5
ABF, axillobifemoral bypass; ICV, ileocecal valve; SMA, superior mesenteric artery.
Cecal tubulovillous adenoma None, bleeding duodenal ulcer None
2017
M
-, -
2010 82
Volume
Moseley et al.36
6 Case Report
adenocarcinomaeinduced mucosal disruption due to tumor-mediated ulceration allowing subsequent inoculation of the bloodstream. Nevertheless, other malignancies are also associated with C. septicum bacteremia. C. septicum bacteremia has also been associated with hematologic malignancy. Kornbluth et al.50 found that 40% of patients with C. septicum infection had an associated hematologic malignancy, but our review demonstrates that once vascular complications are present in the context of C. septicum bacteremia it is less likely to be associated with a hematologic malignancy (3.9%, 2 of 51 reported). The hematologic malignancies include Waldenstrom macroglobulinemia and plasma cell myeloma.5,35 Interestingly, our review showed that one of the two patients with reported hematologic malignancy had a concomitant colonic malignancy. This updated review of C. septicum vasculitis confers an overall mortality of 57% (29 of 51 reported). While 16 of the 16 patients who did not undergo vascular operative intervention died within 5 weeks, most patients died before planned surgical intervention or surgery was not recommended due to medical instability. Mean reported survival among this group was 11.1 days from presentation. Successful outcomes have been observed with several treatment strategies including: (1) establishing early targeted antibiotic therapy, (2) surgical resection of diseased vascular lesions, and (3) identification and treatment of the associated malignancy. The presence of concomitant malignancy may vary, but the need to eliminate the nidus of bacteremia is crucial. As such, the presence of C. septicum should prompt early diagnostic imaging in an effort to identify potential vascular involvement. In addition, C. septicum bacteremia, especially in the presence of vascular seeding, warrants early colonoscopy and hematologic work-up to identify a source of infection and potential synchronous neoplasm. Facilitating early surgical intervention is crucial to optimizing outcomes as confirmed by this review. The rarity of this disease limits high-quality studies, but this systematic review attempts to provide evidence to uncover ideal variable treatment strategies. The importance of this case report and review is to contribute further data and successful treatment strategies to what is classically considered a deadly disease. REFERENCES 1. Alpern RJ, Dowell V. Clostridium septicum infections and malignancy. JAMA 1969;209:385e8.
Annals of Vascular Surgery
2. Seder CW, Kramer M, Long G, et al. Clostridium septicum aortitis: Report of two cases and review of the literature. J Vasc Surg 2009;49:1304e9. 3. Bridges RA, McTamaney JP, Barnes RW. Recognition and management of ruptured infected aneurysm of the abdominal aorta. Vasc Endovascular Surg 1981;15:360e5. 4. Semel L, Aikman WO, Parker FB Jr, et al. Nontraumatic clostridial myonecrosis and mycotic aneurysm formation. NY State J Med 1984;84:195e6. 5. Kaufman JL, Fereshetian A, Chang B, et al. Septicemia presenting with endoaneurysmal gas: CT demonstration. AJR Am J Roentgenol 1988;151:287e8. 6. Narula A, Lake SP, Baker AR, et al. Mycotic aneurysm of the popliteal artery following right hemicolectomy. Postgrad Med J 1988;64:638e9. 7. Momont SL, Overholt EL. Aortitis due to metastatic gas gangrene. Wis Med J 1989;88:28e30. 8. Asplund MW, Molinaro A. Infected solitary iliac artery aneurysm. J Vasc Surg 1990;12:219e20. 9. Brahan RB, Kahler RC. Clostridium septicum as a cause of pericarditis and mycotic aneurysm. J Clin Microbiol 1990;28:2377e8. 10. Hurley L, Howe K. Mycotic aortic aneurysm infected by clostridium septicumea case history. Angiology 1991;42: 585e9. 11. Christensen J, Bistrup C. Emphysematous pyelonephritis caused by clostridium septicum and complicated by a mycotic aneurysm. Br J Radiol 1993;66:842e3. 12. de Gara CJ, Mandel LA. Invasive Clostridium septicum infection in association with colorectal carcinoma. Can J Surg 1994;37:371. 13. Messa C, Kulkarni M, Arous E. Double clostridial mycotic aneurysms of the aorta. Vascular 1995;3:687e92. 14. Upchurch GR, Clair DG, Whittemore AD, et al. Clostridium septicum bacteremia associated with aortic graft infection. J Vasc Surg 1995;22:493e5. 15. Murphy DP, Glazier DB, Krause TJ. Mycotic aneurysm of the thoracic aorta caused by clostridium septicum. Ann Thorac Surg 1996;62:1835e7. 16. Sailors DM, Eidt JF, Gagne PJ, et al. Primary clostridium septicum aortitis: A rare cause of necrotizing suprarenal aortic infection: A case report and review of the literature. J Vasc Surg 1996;23:714e8. 17. Monsen T, Palmgren H, Arnerl€ ov C. Aortic dissection due to Clostridium septicum infection. Eur J Vasc Endovasc Surg 1997;13:517e8. 18. Montoya FJ, Weinstein-Moreno LF, Johnson CC. Mycotic thoracic aneurysm due to Clostridium septicum and occult adenocarcinoma of the cecum. Clin Infect Dis 1997;24:1007. 19. Cohen CA, Almeder LM, Israni A, et al. Clostridium septicum endocarditis complicated by aortic-ring abscess and aortitis. Clin Infect Dis 1998;26:495e6. 20. Johnson FE. Infected aortic aneurysm. Am J Surg 1999;178: 268. 21. Morrison RC, Dimuzio PJ, Kahn M, et al. Clostridial mycotic aneurysm of the thoracoabdominal aorta: A case report. Vasc Endovascular Surg 2001;35:303e10. 22. Al Bahrani BJ, Thomas DJ, Moylan EJ. What’s causing that gas? Med J Aust 2001;174:652. 23. Munshi IA, Rhee SW, Pane T, et al. Clostridium septicum mycotic aortic aneurysm. Am J Surg 2002;184:54e5. 24. Zenati MA, Bonanomi G, Kostov D, et al. Images in cardiovascular medicine. Fulminant Clostridium septicum aortitis. Circulation 2002;105:1871.
Volume
-, -
2017
25. Liechti M, Sch€ ob O, Kacl G, et al. Clostridium septicum aortitis in a patient with colon carcinoma. Eur J Clin Microbiol Infect Dis 2003;22:632e4. 26. Takano H, Taniguchi K, Kuki S, et al. Mycotic aneurysm of the infrarenal abdominal aorta infected by Clostridium septicum: A case report of surgical management and review of the literature. J Vasc Surg 2003;38:847e51. 27. Davies M, Byrne J, Harvey JS. Clostridial infection of the abdominal aorta. J Am Coll Surg 2003;197:331. 28. Rucker CM, Menias CO, Bhalla S, et al. Clostridium septicum infrarenal aortitis secondary to occult cecal adenocarcinoma. Am J Roentgenol 2004;183:1316e8. 29. Evans LT, Chey WD. Clostridial aortitis and colon cancer. Gastrointest Endosc 2004;60:803. 30. Mohamed HK, Elliott BM, Brothers TE, et al. Suprarenal Clostridium septicum aortitis with rupture and simultaneous colon cancer. Ann Vasc Surg 2006;20:825e9. 31. Asciutto G, Geier B, Marpe B, et al. A case of contained ruptured aortitis due to Clostridium septicum infection in a patient with a colon malignancy. Chir Ital 2007;59:743. 32. Laudito A, Gai V, Battista S, et al. Clostridium septicum arch aortitis. Circulation 2008;117:1609. 33. Gai V, Battista S, Bonino L. Electronic clinical challenges and images in GI. Clostridium septicum arch aortitis. Gastroenterology 2009;136:e4e5. 34. Yang Z, Reilly SD. Clostridium septicum aortitis causing aortic dissection in a 22-year-old man. Tex Heart Inst J 2009;36:334e6. 35. Dulaney E, Kida M, Evans M, et al. Aortic rupture due to clostridium septicum: A cause of cardiac tamponade. Lab Invest 2010;90:5Ae6A. 36. Moseley B, Mwirigi NW, Bowen J. Clostridium septicum aortitis and cecal adenocarcinoma. Case Rep Med 2010;2010:121728. 37. Colwick SE, Alkhoury F, Martin JT, et al. Abdominal aortic aneurysm repair complicated by infection with Clostridium septicum. Ann Vasc Surg 2011;25:839.e11e3. 38. Granier M, Granier A, Fraga J, et al. Emphysematous infectious aortitis: A dramatic evolution. Eur Heart J 2011;32:2085.
Case Report 7
39. Mao E, Clements A, Feller E. Clostridium septicum sepsis and colon carcinoma: Report of 4 cases. Case Rep Med 2011;2011:248453. 40. Annapureddy N, Agarwal SK, Kanakadandi V, et al. Clostridium septicum aortitis in a patient with extensive atheromatous disease of the aorta. J Infect Chemother 2012;18:948e50. 41. Demidovich J, Condoluci M, Fussa M, et al. A 69-year-old woman with persistent back pain. Clin Infect Dis 2012;55: 301e2. 42. Phillip SG, de Virgilio C. Clostridium septicum aortitis with associated sigmoid colon adenocarcinoma. Ann Vasc Surg 2012;26:280.e1e4. 43. Khalid M, Lazarus R, Bowler IC, et al. Clostridium septicum sepsis and its implications. BMJ Case Rep 2012;2012. http:// dx.doi.org/10.1136/bcr-2012-006167. 44. Mbianda CN, Yacub J, Phan P, et al. An incidental aortic ulcer in a patient diagnosed with colon cancer: Hickam’s dictum versus occam’s razor. J Gen Intern Med 2012;27: S389. 45. Tokmaji G, Gosev I, Kumamaru KK, et al. Mycotic aneurysm of the aortic arch presenting with left vocal cord palsy. Ann Thorac Surg 2013;96:302e5. 46. Al Hadi HI, Patel G, Rees MD. A rare case of clostridium septicum mycotic aortic arch aneurysm following open right hemicolectomy for colorectal cancer. BMJ Case Rep 2014;2014. http://dx.doi.org/10.1136/bcr-2014-204636. 47. Eplinius F, H€adrich C. Acute aortic dissection caused by Clostridium septicum aortitis. Forensic Sci Int 2014;244: e38e41. 48. Hashimoto T, Okamatsu Y, Hyakuna Y, et al. Perianeurysmal emphysema: Clostridium septicum-infected aortic aneurysm. Circulation 2014;129:1900e1. 49. Lintin L, Wheeler R, Whiston R, et al. Mycotic thoracic aortic arch aneurysm from haematogenous spread of Clostridium septicum due to metastatic colorectal cancer: A survival guide. J Surg Case Rep 2014;2014. http://dx.doi.org/ 10.1093/jscr/rju117. 50. Kornbluth AA, Danzig JB, Bernstein LH. Clostridium septicum infection and associated malignancy: Report of 2 cases and review of the literature. Medicine 1989;68:30e7.
Clostridium septicum is a rare organism, accounting for approximately 1.3% of clostridial infections and is associated with synchronous colonic malignancy. This case report describes a patient successfully treated for a mycotic aortic aneurysm secondary to C. septicum bacteremia. Subsequent evaluation confirmed a colonic malignancy, prompting early intervention. A systematic literature review revealing a rate of gastrointestinal malignancy in this patient population is 71%, and hematologic malignancy is 3.9%, with the remaining cohort of patients having an unknown source. Infectious involvement of the aorta and associated vascular structures portends a poor prognosis with a 57% mortality rate. Our case and updated review demonstrates the implications of C. septicum vascular seeding and subsequent treatment outcomes.
Clostridium septicum is a very rare gram-positive spore-forming motile bacillus1 associated with colonic malignancy and has a propensity for aortic seeding. A heightened awareness of the increased risk of concomitant colonic malignancy and aortic involvement should prompt early diagnostic imaging. Although few cases have been reported in the literature, there is mounting evidence that early initiation of targeted antibiotic therapy and surgical intervention decreases morbidity and mortality. This case report describes the surgical and medical
Conflict of interest: The authors declare no conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 1 Department of Surgery, Medstar Georgetown University Hospital, Washington, DC. 2 Georgetown University School of Medicine, Washington, DC. 3
Virginia Hospital Center, Arlington, VA.
Correspondence to: C. Francisco Espinel, MD, Virginia Hospital Center 1625 N. George Mason Drive, Suite 334, Arlington, VA 22205, USA; E-mail: [email protected] Ann Vasc Surg 2017; -: 1–7 http://dx.doi.org/10.1016/j.avsg.2017.03.178 Ó 2017 Elsevier Inc. All rights reserved. Manuscript received: January 29, 2017; manuscript accepted: March 28, 2017; published online: - - -
management of a 66-year-old male with C. septicum bacteremia with a mycotic aneurysm and a synchronous colonic malignancy. In addition, a systematic literature review was completed to assess concurrent neoplasms associated with C. septicum vascular seeding to define the outcomes in this cohort of patients.
CASE REPORT A 66-year-old, otherwise healthy male, presented with a 48-hour duration of increasing, diffuse abdominal pain radiating to his back with associated subjective fever and chills. The patient had not sought medical care in over 15 years, but a visit to an urgent care clinic following the onset of symptoms was suspected to be muscular pain in origin. Days prior, he was treated with a muscle relaxant and opioid pain medication without resolution. On evaluation, the patient was febrile to 101.3 F, and a computed tomography scan revealed a mycotic aneurysm of the infrarenal aorta with evidence of necrotizing aortitis (Fig. 1). No bowel abnormalities or masses were observed. Blood cultures were obtained, and broad-spectrum intravenous antibiotic therapy (vancomycin and piperacillin/ tazobactam) was initiated. The patient remained hemodynamically stable and was immediately taken to the operating room. Surgical 1
2 Case Report
Fig. 1. A coronal (A) and transverse view (B) of the computed tomography scan showing a fusiform aneurysmal dilatation of the infrarenal abdominal aorta
intervention consisted of excision of the infrarenal abdominal aortic aneurysm with a right axillofemoral bypass using a Gore-Tex (Gore Medical Products, Flagstaff, AZ) graft, and a right-to-left femoral-femoral (end-to-side) bypass using the same prosthetic material. The patient recovered without complication, and intraoperative blood cultures revealed growth of C. septicum. The association of this rare organism with a concurrent colonic neoplasm prompted a colonoscopy during the same hospital stay. Colonoscopy revealed an ascending colon mass, which was biopsied with pathology demonstrating severe glandular dysplasia with atypical cytologic features, without definitive invasion. Following convalescence from the aforementioned surgery and discharge, the patient remained on intravenous ertapenem daily for 6 weeks, with ultimate resolution of bacteremia. Four weeks later, the patient returned to the operating room for a laparoscopic right hemicolectomy and recovered without complication. The lesion measured 7.5 4.5 4 cm with moderately differentiated invasive adenocarcinoma (pT3pN0pM0). Upon 20-month follow-up, the patient was without recurrence.
DISCUSSION C. septicum is not a typical organism of the gut flora, and the specific entity remains incredibly rare accounting for approximately 1% of all clostridium infections. Seder et al.2 have described the association of C. septicum infections and the development of aortitis, aneurysm, and aortic dissection. However, the C. septicumeassociated literature has expanded since that review. We performed a systematic literature review as outlined in Figure 2 to identify the published cases of C. septicum with vascular seeding. To date, including our patient, 51 cases of C. septicum aortitis have been documented (Table I), and 71% (n ¼ 36) are associated with a concurrent gastrointestinal malignancy or premalignant lesion. It is
Annals of Vascular Surgery
measuring 4.4 4.7 cm (arrow) in greatest dimension. Foci of gas along the intima of the aorta are depicted with arrowheads.
Fig. 2. Flowchart depicting the systematic selection process for inclusion and exclusion of articles in the review. The MEDLINE (via PubMed) and EMBASE databases were queried using controlled vocabulary terms where appropriate (Medical Subject Heading and Emtree terms) in combination with relevant keywords and phrases. The search strategy focused on Clostridium septicum, colonic neoplasms, malignancies, aortitis, and aneurysm in combination with the Boolean operators AND or OR for articles published up until May 15, 2016. A total of 145 articles were obtained from this search after duplications were removed. Of these articles, 93 articles were excluded on the basis of lack of including vascular pathology. A full-text review of 52 articles was completed.
believed that the pH, electrolyte, and osmotic composition of the cecum provide an environment that is ideal for the growth of C. septicum.2 The postulated mechanism of infection involves colonic
Table I. Cases of Clostridium septicum with vascular involvement Year
Bridges et al.3
Age
Process
Location
Neoplasm
Surgery
1981 68
M
No
Aneurysm
Infrarenal
Unknown
ABF, omental patch
Semel et al.4
1984 60
F
No
Aneurysm
Ascending/arch
Kaufman et al.5
1988 62
M
Narula et al.6
1988 76
M
Unknown Dissection/ aneurysm No Aneurysm
Popliteal
Transverse colon adenocarcinoma Waldenstrom macroglobulinemia Colon adenocarcinoma
Momont and Overholt7 Asplund and Molinaro8
1989 85
F
No
1990 80
Brahan and Kahler9
Iliac and femoral
Alive, duration unknown Partial colectomy Died, 20 hours postoperatively None Died 6 hours after admission Ligation and excision of Alive, duration aneurysm, right unknown hemicolectomy None Died
Cecal adenocarcinoma
Iliac
Cecal carcinoma
1990 70
F
Yes
Aneurysm
Arch/descending
Ascending colon adenocarcinoma
Hurley and Howe10
1991 67
M
Yes
Aneurysm
Infrarenal
Rectal, colonic adenomas
Christensen and Bistrup11 de Gara and Mandel12 Messa et al.13
1993 74
F
Yes
Aneurysm
Juxtarenal
None
Aneurysm excision, extraanatomic femoral-femoral bypass, right hemicolectomy In situ graft, resection of PA to aneurysm fistula Right ABF, aneurysm resection, left ABF for infected graft None
1994 56
M
No
Aneurysm
Infrarenal
Crohn’s disease
Aneurysm repair
1995 77
M
Yes
Double aneurysm
Sigmoid adenocarcinoma
Upchurch et al.14
1995 67
M
Yes
Graft
Descending thoracic/ juxtarenal Abdominal
Murphy et al.15
1996 78
M
No
Aneurysm
In situ thoracic graft with omental flap and ABF ABF and removal of graft, right hemicolectomy, In situ graft and esophagectomy
Sailors et al.16 Monsen et al.17
1996 74 1997 81
F M
No No
Aneurysm Dissection
Montoya et al.18
1997 78
M
Unknown Aneurysm
Proximal descending thoracic Thoracoabdominal Ascending to infrarenal Descending thoracic
Benign sigmoid polyps
None Cecal adenocarcinoma
In situ graft In situ
Cecal adenocarcinoma
None
Died, 10 months postoperatively
Alive at 36 months
Alive at 9 months
Died Alive, unknown duration Alive at 4 months
Alive at 3 years
Alive at 6 months
Died, 3.5 months later Died 5 hours postoperatively Died, 16 hours after admission (Continued)
Case Report 3
Ascending/arch
M
Dissection/ aneurysm Unknown Aneurysm
Ascending colon adenocarcinoma
Outcome
2017
Diabetic
-, -
Sex
Volume
Author
Author
Year
Cohen et al.19 Johnson20 Morrison et al.21
Age
Diabetic
Process
1998 77
M
1999 78 2001 71
M M
Unknown Dissection/ abscess Yes Aneurysm No Aneurysm
Al Bahrani et al.22 2001 63
M
Unknown Aneurysm
Munshi et al.23 Zenati et al.24
2002 78 2002 87
M M
Liechti et al.25
2003 55
M
No Aneurysm Unknown Dissection/ aneurysm No Aneurysm
Takano et al.26
2003 69
M
Unknown Aneurysm
Davies et al.27
2003 63
M
No
Aneurysm
Infrarenal
Unknown
Rucker et al.28
2004 77
F
No
Aneurysm
Infrarenal
Cecal adenocarcinoma
Rucker et al.28
2004 91
F
No
Aortitis
Evans and Chey29
2004 91
F
Unknown Aortitis
SMA to iliac arteries Abdominal
Mohamed et al.30
2006 82
M
No
Juxtarenal
Asciutto et al.31
2007 71
M
Unknown Aortitis
Juxtarenal
Ascending adenocarcinoma Transverse colon adenocarcinoma Ascending adenocarcinoma Ascending colon adenocarcinoma
Laudito et al.32
2008 74
F
Yes
Arch/ascending
Seder et al.2
2008 75
M
Seder et al.2
2008 76
Gai et al.33
Aneurysm
Location
Neoplasm
Aortic root/ Cecal adenocarcinoma ascending Infrarenal Unknown Thoracoabdominal Ascending colon adenocarcinoma Infrarenal Ascending colon adenocarcinoma Infrarenal Cecal adenoma Innominate Cecal adenocarcinoma to renal arteries Infrarenal Transverse colon adenocarcinoma Infrarenal Ascending colon adenocarcinoma
Surgery
Outcome
Right hemicolectomy
Died, hospital day 33
None In situ
Died, hospital day 6 Alive at 36 months
Unspecified reconstruction None None
Alive, unknown duration Died, 1 month later Died, on hospital day 6
Exploration of aorta, transverse colectomy In situ with omental flap revised to a rectus abdominus flap, right hemicolectomy ABF
Died, 5 month later
ABF, right hemicolectomy Right colectomy Extended right hemicolectomy In situ graft, right hemicolectomy In situ graft and wide tissue debridement, right hemicolectomy ABF, hemicolectomy
No
Aortitis/ dissection Aneurysm
Infrarenal
F
No
Aneurysm
Juxtarenal
Adenocarcinoma descending colon Ascending adenocarcinoma Cecal adenocarcinoma
2009 76
F
Yes
Arch/descending
Colon adenocarcinoma
ABF, right hemicolectomy ABF, right hemicolectomy ABF, hemicolectomy
Yang and Reilly34
2009 22
M
Entire aorta
None
None
Dulaney et al.35
2010 74
M
Ascending aorta
Plasma cell myeloma, rectal adenocarcinoma
None
Aortitis/ dissection No Aortitis/ dissection Unknown Dissection/ abscess
Alive at 60 months
Died, 2 days postoperatively Died, 42 days postoperatively Unknown Died, 5 months later Alive at 15 months Alive, unknown duration Alive, unknown duration Died, 4 months later Died, 3 months later Alive, unknown duration Died, 8 hours after presentation Died, hospital day 7
Annals of Vascular Surgery
Sex
4 Case Report
Table I. Continued
Yes
Colwick et al.37
2011 82
M
Unknown Aneurysm
Granier et al.38
2011 83
M
Unknown Aortitis
Mao et al.39
2011 73
M
Unknown Aortitis
Annapureddy et al.40 Demidovich et al.41 Phillip and de Virgilio42 Khalid et al.43
2012 69
M
No
2012 69
F
2012 87
M
Aortitis with Infrarenal aneurysm Unknown Aneurysm Descending thoracic Yes Aortitis Juxtarenal
2012 77
M
Unknown Aneurysm
Infrarenal
Mbianda et al.44 Present case report
2012 73 2013 66
M M
Unknown Aortitis No Aneurysm
Arch Infrarenal
Cecal adenocarcinoma Ascending colon adenocarcinoma
Tokmaji et al.45
2013 71
M
Unknown Aneurysm
Abdominal
None
Al Hadi et al.46
2014 63
M
Unknown Aneurysm
Eplinius and Hadrich47
2014 32
M
No
Dissection
Hashimoto et al.48
2014 81
M
No
Aneurysm
Lintin et al.49
2014 78
F
Unknown Aneurysm
Arch/ descending Ascending/ descending thoracic Arch/ descending Thoracic aorta
Aortitis Juxtarenal, previous graft Descending thoracic Unknown
Right hemicolectomy
Died, 75 days after admission ABF with graft, omental Alive, unknown patch duration None Died, hospital day 3
Cecal adenocarcinoma
None
None
ABF with graft, none
Died, during hospitalization Alive at 6 months
Unspecified colonic mass Sigmoid adenocarcinoma Multifocal colonic adenocarcinoma
None
Died before surgery
None
Died, 5 weeks later Alive, unknown duration
Ascending colon adenocarcinoma None
Resection of aneurysm with graft, right hemicolectomy Resection aortic arch ABF, femoral-femoral bypass, excision of aneurysm, right hemicolectomy ABF with femoralfemoral bypass None, right hemicolectomy None
Unknown
None
Died, hospital day 6
ICV colon adenocarcinoma, liver metastasis
Right-to-left common carotid crossover bypass, left common carotid to left subclavian bypass (double transposition), right hemicolectomy
Alive at 28 months
Died postoperatively Alive at 20 months
Alive at 2 months Died, hospital day 3 Died, 6 days after presentation
Case Report 5
ABF, axillobifemoral bypass; ICV, ileocecal valve; SMA, superior mesenteric artery.
Cecal tubulovillous adenoma None, bleeding duodenal ulcer None
2017
M
-, -
2010 82
Volume
Moseley et al.36
6 Case Report
adenocarcinomaeinduced mucosal disruption due to tumor-mediated ulceration allowing subsequent inoculation of the bloodstream. Nevertheless, other malignancies are also associated with C. septicum bacteremia. C. septicum bacteremia has also been associated with hematologic malignancy. Kornbluth et al.50 found that 40% of patients with C. septicum infection had an associated hematologic malignancy, but our review demonstrates that once vascular complications are present in the context of C. septicum bacteremia it is less likely to be associated with a hematologic malignancy (3.9%, 2 of 51 reported). The hematologic malignancies include Waldenstrom macroglobulinemia and plasma cell myeloma.5,35 Interestingly, our review showed that one of the two patients with reported hematologic malignancy had a concomitant colonic malignancy. This updated review of C. septicum vasculitis confers an overall mortality of 57% (29 of 51 reported). While 16 of the 16 patients who did not undergo vascular operative intervention died within 5 weeks, most patients died before planned surgical intervention or surgery was not recommended due to medical instability. Mean reported survival among this group was 11.1 days from presentation. Successful outcomes have been observed with several treatment strategies including: (1) establishing early targeted antibiotic therapy, (2) surgical resection of diseased vascular lesions, and (3) identification and treatment of the associated malignancy. The presence of concomitant malignancy may vary, but the need to eliminate the nidus of bacteremia is crucial. As such, the presence of C. septicum should prompt early diagnostic imaging in an effort to identify potential vascular involvement. In addition, C. septicum bacteremia, especially in the presence of vascular seeding, warrants early colonoscopy and hematologic work-up to identify a source of infection and potential synchronous neoplasm. Facilitating early surgical intervention is crucial to optimizing outcomes as confirmed by this review. The rarity of this disease limits high-quality studies, but this systematic review attempts to provide evidence to uncover ideal variable treatment strategies. The importance of this case report and review is to contribute further data and successful treatment strategies to what is classically considered a deadly disease. REFERENCES 1. Alpern RJ, Dowell V. Clostridium septicum infections and malignancy. JAMA 1969;209:385e8.
Annals of Vascular Surgery
2. Seder CW, Kramer M, Long G, et al. Clostridium septicum aortitis: Report of two cases and review of the literature. J Vasc Surg 2009;49:1304e9. 3. Bridges RA, McTamaney JP, Barnes RW. Recognition and management of ruptured infected aneurysm of the abdominal aorta. Vasc Endovascular Surg 1981;15:360e5. 4. Semel L, Aikman WO, Parker FB Jr, et al. Nontraumatic clostridial myonecrosis and mycotic aneurysm formation. NY State J Med 1984;84:195e6. 5. Kaufman JL, Fereshetian A, Chang B, et al. Septicemia presenting with endoaneurysmal gas: CT demonstration. AJR Am J Roentgenol 1988;151:287e8. 6. Narula A, Lake SP, Baker AR, et al. Mycotic aneurysm of the popliteal artery following right hemicolectomy. Postgrad Med J 1988;64:638e9. 7. Momont SL, Overholt EL. Aortitis due to metastatic gas gangrene. Wis Med J 1989;88:28e30. 8. Asplund MW, Molinaro A. Infected solitary iliac artery aneurysm. J Vasc Surg 1990;12:219e20. 9. Brahan RB, Kahler RC. Clostridium septicum as a cause of pericarditis and mycotic aneurysm. J Clin Microbiol 1990;28:2377e8. 10. Hurley L, Howe K. Mycotic aortic aneurysm infected by clostridium septicumea case history. Angiology 1991;42: 585e9. 11. Christensen J, Bistrup C. Emphysematous pyelonephritis caused by clostridium septicum and complicated by a mycotic aneurysm. Br J Radiol 1993;66:842e3. 12. de Gara CJ, Mandel LA. Invasive Clostridium septicum infection in association with colorectal carcinoma. Can J Surg 1994;37:371. 13. Messa C, Kulkarni M, Arous E. Double clostridial mycotic aneurysms of the aorta. Vascular 1995;3:687e92. 14. Upchurch GR, Clair DG, Whittemore AD, et al. Clostridium septicum bacteremia associated with aortic graft infection. J Vasc Surg 1995;22:493e5. 15. Murphy DP, Glazier DB, Krause TJ. Mycotic aneurysm of the thoracic aorta caused by clostridium septicum. Ann Thorac Surg 1996;62:1835e7. 16. Sailors DM, Eidt JF, Gagne PJ, et al. Primary clostridium septicum aortitis: A rare cause of necrotizing suprarenal aortic infection: A case report and review of the literature. J Vasc Surg 1996;23:714e8. 17. Monsen T, Palmgren H, Arnerl€ ov C. Aortic dissection due to Clostridium septicum infection. Eur J Vasc Endovasc Surg 1997;13:517e8. 18. Montoya FJ, Weinstein-Moreno LF, Johnson CC. Mycotic thoracic aneurysm due to Clostridium septicum and occult adenocarcinoma of the cecum. Clin Infect Dis 1997;24:1007. 19. Cohen CA, Almeder LM, Israni A, et al. Clostridium septicum endocarditis complicated by aortic-ring abscess and aortitis. Clin Infect Dis 1998;26:495e6. 20. Johnson FE. Infected aortic aneurysm. Am J Surg 1999;178: 268. 21. Morrison RC, Dimuzio PJ, Kahn M, et al. Clostridial mycotic aneurysm of the thoracoabdominal aorta: A case report. Vasc Endovascular Surg 2001;35:303e10. 22. Al Bahrani BJ, Thomas DJ, Moylan EJ. What’s causing that gas? Med J Aust 2001;174:652. 23. Munshi IA, Rhee SW, Pane T, et al. Clostridium septicum mycotic aortic aneurysm. Am J Surg 2002;184:54e5. 24. Zenati MA, Bonanomi G, Kostov D, et al. Images in cardiovascular medicine. Fulminant Clostridium septicum aortitis. Circulation 2002;105:1871.
Volume
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2017
25. Liechti M, Sch€ ob O, Kacl G, et al. Clostridium septicum aortitis in a patient with colon carcinoma. Eur J Clin Microbiol Infect Dis 2003;22:632e4. 26. Takano H, Taniguchi K, Kuki S, et al. Mycotic aneurysm of the infrarenal abdominal aorta infected by Clostridium septicum: A case report of surgical management and review of the literature. J Vasc Surg 2003;38:847e51. 27. Davies M, Byrne J, Harvey JS. Clostridial infection of the abdominal aorta. J Am Coll Surg 2003;197:331. 28. Rucker CM, Menias CO, Bhalla S, et al. Clostridium septicum infrarenal aortitis secondary to occult cecal adenocarcinoma. Am J Roentgenol 2004;183:1316e8. 29. Evans LT, Chey WD. Clostridial aortitis and colon cancer. Gastrointest Endosc 2004;60:803. 30. Mohamed HK, Elliott BM, Brothers TE, et al. Suprarenal Clostridium septicum aortitis with rupture and simultaneous colon cancer. Ann Vasc Surg 2006;20:825e9. 31. Asciutto G, Geier B, Marpe B, et al. A case of contained ruptured aortitis due to Clostridium septicum infection in a patient with a colon malignancy. Chir Ital 2007;59:743. 32. Laudito A, Gai V, Battista S, et al. Clostridium septicum arch aortitis. Circulation 2008;117:1609. 33. Gai V, Battista S, Bonino L. Electronic clinical challenges and images in GI. Clostridium septicum arch aortitis. Gastroenterology 2009;136:e4e5. 34. Yang Z, Reilly SD. Clostridium septicum aortitis causing aortic dissection in a 22-year-old man. Tex Heart Inst J 2009;36:334e6. 35. Dulaney E, Kida M, Evans M, et al. Aortic rupture due to clostridium septicum: A cause of cardiac tamponade. Lab Invest 2010;90:5Ae6A. 36. Moseley B, Mwirigi NW, Bowen J. Clostridium septicum aortitis and cecal adenocarcinoma. Case Rep Med 2010;2010:121728. 37. Colwick SE, Alkhoury F, Martin JT, et al. Abdominal aortic aneurysm repair complicated by infection with Clostridium septicum. Ann Vasc Surg 2011;25:839.e11e3. 38. Granier M, Granier A, Fraga J, et al. Emphysematous infectious aortitis: A dramatic evolution. Eur Heart J 2011;32:2085.
Case Report 7
39. Mao E, Clements A, Feller E. Clostridium septicum sepsis and colon carcinoma: Report of 4 cases. Case Rep Med 2011;2011:248453. 40. Annapureddy N, Agarwal SK, Kanakadandi V, et al. Clostridium septicum aortitis in a patient with extensive atheromatous disease of the aorta. J Infect Chemother 2012;18:948e50. 41. Demidovich J, Condoluci M, Fussa M, et al. A 69-year-old woman with persistent back pain. Clin Infect Dis 2012;55: 301e2. 42. Phillip SG, de Virgilio C. Clostridium septicum aortitis with associated sigmoid colon adenocarcinoma. Ann Vasc Surg 2012;26:280.e1e4. 43. Khalid M, Lazarus R, Bowler IC, et al. Clostridium septicum sepsis and its implications. BMJ Case Rep 2012;2012. http:// dx.doi.org/10.1136/bcr-2012-006167. 44. Mbianda CN, Yacub J, Phan P, et al. An incidental aortic ulcer in a patient diagnosed with colon cancer: Hickam’s dictum versus occam’s razor. J Gen Intern Med 2012;27: S389. 45. Tokmaji G, Gosev I, Kumamaru KK, et al. Mycotic aneurysm of the aortic arch presenting with left vocal cord palsy. Ann Thorac Surg 2013;96:302e5. 46. Al Hadi HI, Patel G, Rees MD. A rare case of clostridium septicum mycotic aortic arch aneurysm following open right hemicolectomy for colorectal cancer. BMJ Case Rep 2014;2014. http://dx.doi.org/10.1136/bcr-2014-204636. 47. Eplinius F, H€adrich C. Acute aortic dissection caused by Clostridium septicum aortitis. Forensic Sci Int 2014;244: e38e41. 48. Hashimoto T, Okamatsu Y, Hyakuna Y, et al. Perianeurysmal emphysema: Clostridium septicum-infected aortic aneurysm. Circulation 2014;129:1900e1. 49. Lintin L, Wheeler R, Whiston R, et al. Mycotic thoracic aortic arch aneurysm from haematogenous spread of Clostridium septicum due to metastatic colorectal cancer: A survival guide. J Surg Case Rep 2014;2014. http://dx.doi.org/ 10.1093/jscr/rju117. 50. Kornbluth AA, Danzig JB, Bernstein LH. Clostridium septicum infection and associated malignancy: Report of 2 cases and review of the literature. Medicine 1989;68:30e7.