Jpn J Radiol (2014) 32:113–116 DOI 10.1007/s11604-013-0273-x
CASE REPORT
Simultaneous thrombosis of superior mesenteric artery and superior mesenteric vein following chemotherapy: MDCT findings Deniz Cebi Olgun • Selim Bakan • Cesur Samanci • Onur Tutar • Suleyman Demiryas • Bora Korkmazer Fatih Kantarci
•
Received: 5 November 2013 / Accepted: 14 December 2013 / Published online: 5 January 2014 Ó Japan Radiological Society 2013
Abstract A case of acute mesenteric ischemia due to thrombosis of superior mesenteric artery and vein in a 44-year-old woman following chemotherapy for invasive laryngeal carcinoma was diagnosed on a multi-detector CT scan. Although the link between malignancy and thromboembolism is widely recognized in patients with cancer, chemotherapy further elevates the risk of thrombosis. Acute mesenteric ischemia associated or not associated with chemotherapy rarely occurs in patients with cancer. Moreover, co-occurrence of superior mesenteric artery and superior mesenteric vein thrombosis is reported for the first time.
from 2.5 to 12.5 %, with the rate being contingent upon the type of chemotherapy and other risk factors [2]. In the following report, we present a case of acute mesenteric ischemia in a patient with primary laryngeal carcinoma. Simultaneous thrombosis of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) were diagnosed for the first time in the literature to the best knowledge of the researchers by using multi-detector computed tomography (MDCT).
Keywords Acute Mesenteric ischemia Chemotherapy Thrombosis Multi-detector CT
A 44-year-old woman with a history of laryngeal carcinoma presented with acute severe abdominal pain and abdominal distention. The patient had a 2-month history of hoarseness. Direct laryngoscopy showed a supraglottic vegetating mass with paralyzed right vocal cord, and punch biopsy revealed an invasive squamous cell carcinoma (T2N0M0). She had no daily activity restriction related to any reason. She had been receiving cisplatin 75 mg/day and 5-fluorouracil 750 mg/day for 7 days, and taxotare 75 g/day for 3 days. She had tachycardia (heart rate 108 beats/min) with 130/80 mmHg blood pressure on admission. No additional risk factors such as history of smoking or cardiovascular or prothrombotic disease of any kind were present. Additional sources of embolism were ruled out by echocardiogram, and electrocardiography results revealed normal sinus rhythm. Abdominal examination showed normal bowel sounds and general abdominal distention without rebound tenderness. Laboratory tests indicated C-reactive protein as 413.6 mg/l (normal \10 mg/l), and other laboratory tests were within normal ranges. A standing abdominal plain film showed multiple air and fluid filled dilated loops in the small bowel, which
Introduction Episodes of thrombosis in patients with malignancies are associated commonly, irrespective of concomitant chemotherapy, with increased morbidity and mortality rates. Although pathogenesis of the condition is not clearly understood, it is presumably considered as multifactorial [1]. Chemotherapy is associated with an increased risk of thrombosis. Thrombosis likelihood following chemotherapy ranges D. C. Olgun S. Bakan (&) C. Samanci O. Tutar B. Korkmazer F. Kantarci Department of Radiology, Istanbul University Cerrahpasa Medical Faculty, Kocamustafapasa, 34303 Istanbul, Turkey e-mail: [email protected] S. Demiryas Department of General Surgery, Istanbul University Cerrahpasa Medical Faculty, 34303 Istanbul, Turkey
Case report
123
114
Jpn J Radiol (2014) 32:113–116
Fig. 1 Contrast-enhanced axial (a) and coronal-curved multiplanar reformatted (b) CT images reveal thromboembolic occlusion of SMA (white arrows) and partial thrombosis (ring-like enhancement pattern) of SMV (black arrows). Another axial-reformatted CT image (c) shows slightly dilated jejunum with intramural bowel gas (pneumatosis intestinalis) (white arrow), bowel wall thickening, focal
lack of bowel wall enhancement (black arrow), and mesenteric edema (arrowhead). An unenhanced axial (d) CT shows lack of high density on bowel wall, which signifies absence of necrosis or hemorrhage. There was also no high or low density in the SMV or the SMA, suggesting absence of acute or chronic thrombosis
was indicative of acute small bowel obstruction. Abdominopelvic MDCT examination with intravenous contrast agent was performed using a 16-detector-row-CT (Philips Brilliance 16, Philips Medical Systems, Cleveland, USA). CT parameters included 16 9 1.5 mm detector collimation, 120 kVp, 250 mAs, 0.938 pitch, and slice thickness 3 mm. For contrast-enhanced CT, 80 ml of iodinated contrast material was administered at a rate of 3.4 ml/s, and scanning started with delay times of 30 and 60 s. Abdominopelvic CT pointed to a thromboembolic occlusion of SMA and partial thrombosis (ring-like enhancement pattern) of SMV (Fig. 1a, b). In addition, MDCT scans also indicated a slightly dilated jejunum with intramural bowel gas (pneumatosis intestinalis), bowel wall thickening, focal lack of bowel wall enhancement, and mesenteric edema (Fig. 1c). An unenhanced axial CT shows lack of high density on bowel wall, which signifies absence of necrosis or hemorrhage. There was also no high or low density
in the SMV or the SMA, suggesting absence of acute or chronic thrombosis (Fig. 1d). Laparotomy was performed on the same day and showed necrosis and ischemia on the jejunum (170-cm segment). First, SMA embolectomy was performed using a Fogarty catheter. Then the necrotic segment (Fig. 2) was removed, and end-to-end intestinal anastomosis was done. Following the surgery, her symptoms were attenuated. On the 6th postoperative day, a contrast-enhanced CT revealed normal blood flow in SMA and SMV. After CT examination, she was discharged uneventfully. At a 3-month postoperative follow-up she had no abdominal complaints.
123
Discussion Venous thrombosis and arterial thrombosis in patients with cancer are considered to be multifactorial systemic diseases
Jpn J Radiol (2014) 32:113–116
Fig. 2 Surgical specimen obtained from segmental resection. Resected jejunum shows advanced necrosis
in which several factors such as patient characteristics (age, ethnic background, and obesity), cancer characteristics (primary site of tumor and metastatic disease), and type of cancer treatment (chemotherapy and surgical intervention) contribute to their clinical manifestations [3]. Factors linking thrombosis and thromboembolic events with malignancy and chemotherapy are not entirely clear. One of the proposed explanations is that circulating factors such as ‘‘procoagulant factor’’ are activated by the tumor. Another explanation relies on general factors, which involve immobility or indwelling catheter use. In addition, structural alterations in vascular endothelial cells related to increased tumor neovascularity, or apoptosis induced by chemotherapy in endothelial cells are suggested to play a role. In particular, apoptosis induced by chemotherapy may lead to a weakening of the endothelium which results in exposed basement membrane, and leads to an activation of the coagulation cascade. The same structural alterations can be observed in relation to chemotherapeutic agents, with paradoxical bleeding caused by a leakage of the weakened basement membrane [4]. Some possible causes of thromboembolism (polycythemia vera, pregnancy, abdominal inflammatory conditions, intra-abdominal surgery, abdominal trauma, congestive splenomegaly, cirrhosis, and congestive heart failure) have been described [5]. In our case, these causes were ruled out by her medical history and laboratory examination. However, some prothrombotic states (protein C or S deficiency, factor V Leiden deficiency) could not be ruled out. To the best knowledge of the researchers, if the patient had these states, any thromboembolic event should have been
115
diagnosed in her early adulthood. Nevertheless, in the present case, the mesenteric ischemia was diagnosed during the first episode of chemotherapy. Thus, we may conclude that the synchronous SMA and SMV thromboses are related to chemotherapy. Venous thrombosis is much more common than arterial thrombosis. Accordingly, a study with 1,874 cancer patients showed a rate of 12.3 % for venous thromboembolism while the rate was 1.5 % for arterial thrombosis, and co-occurrence of the two conditions was 0.6 %. In addition, there were only 13 (0.7 %) patients with intraabdominal venous thrombosis, one (0.05 %) patient with ischemic colitis due to occlusion of the celiac artery, and two (0.1 %) patients with mesenteric artery occlusion with or without portal vein thrombosis [3]. Acute myocardial infarction, cerebrovascular events, and peripheral arterial thrombosis are stated to occur in relation to chemotherapy, hormonal treatment, and hematologic growth factors in malignancies. High incidence of thromboembolic events (8.4–17.6 %) has been reported frequently with cisplatin-based chemotherapy. However, arterial thrombosis is rarely seen following treatment with chemotherapy agent 5-fluorouracil [6]. Acute mesenteric ischemia may result from several conditions, including arterial and venous occlusion, strangulating obstruction, and hypoperfusion related to nonocclusive vascular disease. Thromboembolic occlusion of the superior mesenteric artery is strongly linked to arrhythmia, myocardial infarction, valve disease, atherosclerosis, and prolonged hypotension, whereas superior mesenteric vein thrombosis is associated with portal hypertension, venous hypercoagulopathy, and right-sided heart failure [7]. The diagnostic performance of CT for primary mesenteric ischemia has been reported as 64–96 % in sensitivity and 92–100 % in specificity. Alteration of attenuation of the bowel wall on unenhanced CT is not characteristic for arterial occlusion, whereas the bowel wall may appear low density with edema and high with hemorrhage in venous ischemia. However, diminished, absent or target-like enhancement of the bowel wall on contrast-enhanced CT may be seen on both arterial and venous occlusion. The thickness of the intestinal wall may appear thin or normal in arterial ischemia, but it may increase in venous ischemia. Mesenteric fat stranding is commonly seen in strangulating bowel obstruction and veno-occlusive bowel ischemia, whereas it isn’t common in arterial mesenteric ischemia until mesenteric infarction occurs [8]. There are currently very few reports in the literature on acute mesenteric ischemia associated with chemotherapy. Among them, a case of 57-year-old woman with T1N1M0 breast cancer who underwent cyclophosphamide, methotrexate, and 5-fluorouracil treatment was reported [9].
123
116
Another case depicts acute mesenteric ischemia in relation to vincristine, 5-fluorouracil, and cisplatin treatment, in a 46-year-old man with poorly differentiated nasopharyngeal squamous cell carcinoma [10]. To our best knowledge, there is no case of simultaneous thrombosis of SMA and SMV with or without malignancy that has been previously reported in the literature. Acute mesenteric ischemia is a rare, but severe complication of chemotherapy, which must be taken into consideration in carcinomas presenting with abdominal pain and distention. MDCT scans should be performed on these patients in order to enable early diagnosis.
Jpn J Radiol (2014) 32:113–116
3. 4.
5. 6.
7. 8.
Conflict of interest All authors declare that they have no conflict of interest.
References 1. Bick RL. Cancer-associated thrombosis. N Engl J Med. 2003;349:109–11. 2. Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al. Semuloparin for thromboprophylaxis in
123
9.
10.
patients receiving chemotherapy for cancer. N Engl J Med. 2012;366(7):601–9. Amer MH. Cancer-associated thrombosis: clinical presentation and survival. Cancer Manag Res. 2013;26(5):165–78. Elice F, Rodeghiero F, Falanga A, Rickles FR. Thrombosis associated with angiogenesis inhibitors. Best Pract Res Clin Haematol. 2009;22(1):115–28. Singal AK, Kamath PS, Tefferi A. Mesenteric venous thrombosis. Mayo Clin Proc. 2013;88(3):285–94. Heinrich N, Born M, Hoebert E, Verrel F, Simon A, Bode U, et al. Aortobifemoral embolism in an 18-year-old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma. Vasa. 2010;39:271–3. Hoton KM, Fishman EK. Multi-detector row CT of mesenteric ischemia: can it be done? Radiographics. 2001;21:1463–73. Wiesner W, Khurana B, Ji H, Ros PR. CT of acute bowel ischemia. Radiology. 2003;226:635–50. Sugden EM, Griffiths CL, Greywoode GI, Lewis SM. Acute abdomen during adjuvant chemotherapy: superior mesenteric artery thrombosis associated with CMF chemotherapy. Clin Oncol (R Coll Radiol). 2001;13(6):441–3. Allerton R. Acute mesenteric ischaemia associated with 5-FU, cisplatin and vincristine chemotherapy. Clin Oncol (R Coll Radiol). 1996;8(2):116–7.
CASE REPORT
Simultaneous thrombosis of superior mesenteric artery and superior mesenteric vein following chemotherapy: MDCT findings Deniz Cebi Olgun • Selim Bakan • Cesur Samanci • Onur Tutar • Suleyman Demiryas • Bora Korkmazer Fatih Kantarci
•
Received: 5 November 2013 / Accepted: 14 December 2013 / Published online: 5 January 2014 Ó Japan Radiological Society 2013
Abstract A case of acute mesenteric ischemia due to thrombosis of superior mesenteric artery and vein in a 44-year-old woman following chemotherapy for invasive laryngeal carcinoma was diagnosed on a multi-detector CT scan. Although the link between malignancy and thromboembolism is widely recognized in patients with cancer, chemotherapy further elevates the risk of thrombosis. Acute mesenteric ischemia associated or not associated with chemotherapy rarely occurs in patients with cancer. Moreover, co-occurrence of superior mesenteric artery and superior mesenteric vein thrombosis is reported for the first time.
from 2.5 to 12.5 %, with the rate being contingent upon the type of chemotherapy and other risk factors [2]. In the following report, we present a case of acute mesenteric ischemia in a patient with primary laryngeal carcinoma. Simultaneous thrombosis of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) were diagnosed for the first time in the literature to the best knowledge of the researchers by using multi-detector computed tomography (MDCT).
Keywords Acute Mesenteric ischemia Chemotherapy Thrombosis Multi-detector CT
A 44-year-old woman with a history of laryngeal carcinoma presented with acute severe abdominal pain and abdominal distention. The patient had a 2-month history of hoarseness. Direct laryngoscopy showed a supraglottic vegetating mass with paralyzed right vocal cord, and punch biopsy revealed an invasive squamous cell carcinoma (T2N0M0). She had no daily activity restriction related to any reason. She had been receiving cisplatin 75 mg/day and 5-fluorouracil 750 mg/day for 7 days, and taxotare 75 g/day for 3 days. She had tachycardia (heart rate 108 beats/min) with 130/80 mmHg blood pressure on admission. No additional risk factors such as history of smoking or cardiovascular or prothrombotic disease of any kind were present. Additional sources of embolism were ruled out by echocardiogram, and electrocardiography results revealed normal sinus rhythm. Abdominal examination showed normal bowel sounds and general abdominal distention without rebound tenderness. Laboratory tests indicated C-reactive protein as 413.6 mg/l (normal \10 mg/l), and other laboratory tests were within normal ranges. A standing abdominal plain film showed multiple air and fluid filled dilated loops in the small bowel, which
Introduction Episodes of thrombosis in patients with malignancies are associated commonly, irrespective of concomitant chemotherapy, with increased morbidity and mortality rates. Although pathogenesis of the condition is not clearly understood, it is presumably considered as multifactorial [1]. Chemotherapy is associated with an increased risk of thrombosis. Thrombosis likelihood following chemotherapy ranges D. C. Olgun S. Bakan (&) C. Samanci O. Tutar B. Korkmazer F. Kantarci Department of Radiology, Istanbul University Cerrahpasa Medical Faculty, Kocamustafapasa, 34303 Istanbul, Turkey e-mail: [email protected] S. Demiryas Department of General Surgery, Istanbul University Cerrahpasa Medical Faculty, 34303 Istanbul, Turkey
Case report
123
114
Jpn J Radiol (2014) 32:113–116
Fig. 1 Contrast-enhanced axial (a) and coronal-curved multiplanar reformatted (b) CT images reveal thromboembolic occlusion of SMA (white arrows) and partial thrombosis (ring-like enhancement pattern) of SMV (black arrows). Another axial-reformatted CT image (c) shows slightly dilated jejunum with intramural bowel gas (pneumatosis intestinalis) (white arrow), bowel wall thickening, focal
lack of bowel wall enhancement (black arrow), and mesenteric edema (arrowhead). An unenhanced axial (d) CT shows lack of high density on bowel wall, which signifies absence of necrosis or hemorrhage. There was also no high or low density in the SMV or the SMA, suggesting absence of acute or chronic thrombosis
was indicative of acute small bowel obstruction. Abdominopelvic MDCT examination with intravenous contrast agent was performed using a 16-detector-row-CT (Philips Brilliance 16, Philips Medical Systems, Cleveland, USA). CT parameters included 16 9 1.5 mm detector collimation, 120 kVp, 250 mAs, 0.938 pitch, and slice thickness 3 mm. For contrast-enhanced CT, 80 ml of iodinated contrast material was administered at a rate of 3.4 ml/s, and scanning started with delay times of 30 and 60 s. Abdominopelvic CT pointed to a thromboembolic occlusion of SMA and partial thrombosis (ring-like enhancement pattern) of SMV (Fig. 1a, b). In addition, MDCT scans also indicated a slightly dilated jejunum with intramural bowel gas (pneumatosis intestinalis), bowel wall thickening, focal lack of bowel wall enhancement, and mesenteric edema (Fig. 1c). An unenhanced axial CT shows lack of high density on bowel wall, which signifies absence of necrosis or hemorrhage. There was also no high or low density
in the SMV or the SMA, suggesting absence of acute or chronic thrombosis (Fig. 1d). Laparotomy was performed on the same day and showed necrosis and ischemia on the jejunum (170-cm segment). First, SMA embolectomy was performed using a Fogarty catheter. Then the necrotic segment (Fig. 2) was removed, and end-to-end intestinal anastomosis was done. Following the surgery, her symptoms were attenuated. On the 6th postoperative day, a contrast-enhanced CT revealed normal blood flow in SMA and SMV. After CT examination, she was discharged uneventfully. At a 3-month postoperative follow-up she had no abdominal complaints.
123
Discussion Venous thrombosis and arterial thrombosis in patients with cancer are considered to be multifactorial systemic diseases
Jpn J Radiol (2014) 32:113–116
Fig. 2 Surgical specimen obtained from segmental resection. Resected jejunum shows advanced necrosis
in which several factors such as patient characteristics (age, ethnic background, and obesity), cancer characteristics (primary site of tumor and metastatic disease), and type of cancer treatment (chemotherapy and surgical intervention) contribute to their clinical manifestations [3]. Factors linking thrombosis and thromboembolic events with malignancy and chemotherapy are not entirely clear. One of the proposed explanations is that circulating factors such as ‘‘procoagulant factor’’ are activated by the tumor. Another explanation relies on general factors, which involve immobility or indwelling catheter use. In addition, structural alterations in vascular endothelial cells related to increased tumor neovascularity, or apoptosis induced by chemotherapy in endothelial cells are suggested to play a role. In particular, apoptosis induced by chemotherapy may lead to a weakening of the endothelium which results in exposed basement membrane, and leads to an activation of the coagulation cascade. The same structural alterations can be observed in relation to chemotherapeutic agents, with paradoxical bleeding caused by a leakage of the weakened basement membrane [4]. Some possible causes of thromboembolism (polycythemia vera, pregnancy, abdominal inflammatory conditions, intra-abdominal surgery, abdominal trauma, congestive splenomegaly, cirrhosis, and congestive heart failure) have been described [5]. In our case, these causes were ruled out by her medical history and laboratory examination. However, some prothrombotic states (protein C or S deficiency, factor V Leiden deficiency) could not be ruled out. To the best knowledge of the researchers, if the patient had these states, any thromboembolic event should have been
115
diagnosed in her early adulthood. Nevertheless, in the present case, the mesenteric ischemia was diagnosed during the first episode of chemotherapy. Thus, we may conclude that the synchronous SMA and SMV thromboses are related to chemotherapy. Venous thrombosis is much more common than arterial thrombosis. Accordingly, a study with 1,874 cancer patients showed a rate of 12.3 % for venous thromboembolism while the rate was 1.5 % for arterial thrombosis, and co-occurrence of the two conditions was 0.6 %. In addition, there were only 13 (0.7 %) patients with intraabdominal venous thrombosis, one (0.05 %) patient with ischemic colitis due to occlusion of the celiac artery, and two (0.1 %) patients with mesenteric artery occlusion with or without portal vein thrombosis [3]. Acute myocardial infarction, cerebrovascular events, and peripheral arterial thrombosis are stated to occur in relation to chemotherapy, hormonal treatment, and hematologic growth factors in malignancies. High incidence of thromboembolic events (8.4–17.6 %) has been reported frequently with cisplatin-based chemotherapy. However, arterial thrombosis is rarely seen following treatment with chemotherapy agent 5-fluorouracil [6]. Acute mesenteric ischemia may result from several conditions, including arterial and venous occlusion, strangulating obstruction, and hypoperfusion related to nonocclusive vascular disease. Thromboembolic occlusion of the superior mesenteric artery is strongly linked to arrhythmia, myocardial infarction, valve disease, atherosclerosis, and prolonged hypotension, whereas superior mesenteric vein thrombosis is associated with portal hypertension, venous hypercoagulopathy, and right-sided heart failure [7]. The diagnostic performance of CT for primary mesenteric ischemia has been reported as 64–96 % in sensitivity and 92–100 % in specificity. Alteration of attenuation of the bowel wall on unenhanced CT is not characteristic for arterial occlusion, whereas the bowel wall may appear low density with edema and high with hemorrhage in venous ischemia. However, diminished, absent or target-like enhancement of the bowel wall on contrast-enhanced CT may be seen on both arterial and venous occlusion. The thickness of the intestinal wall may appear thin or normal in arterial ischemia, but it may increase in venous ischemia. Mesenteric fat stranding is commonly seen in strangulating bowel obstruction and veno-occlusive bowel ischemia, whereas it isn’t common in arterial mesenteric ischemia until mesenteric infarction occurs [8]. There are currently very few reports in the literature on acute mesenteric ischemia associated with chemotherapy. Among them, a case of 57-year-old woman with T1N1M0 breast cancer who underwent cyclophosphamide, methotrexate, and 5-fluorouracil treatment was reported [9].
123
116
Another case depicts acute mesenteric ischemia in relation to vincristine, 5-fluorouracil, and cisplatin treatment, in a 46-year-old man with poorly differentiated nasopharyngeal squamous cell carcinoma [10]. To our best knowledge, there is no case of simultaneous thrombosis of SMA and SMV with or without malignancy that has been previously reported in the literature. Acute mesenteric ischemia is a rare, but severe complication of chemotherapy, which must be taken into consideration in carcinomas presenting with abdominal pain and distention. MDCT scans should be performed on these patients in order to enable early diagnosis.
Jpn J Radiol (2014) 32:113–116
3. 4.
5. 6.
7. 8.
Conflict of interest All authors declare that they have no conflict of interest.
References 1. Bick RL. Cancer-associated thrombosis. N Engl J Med. 2003;349:109–11. 2. Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al. Semuloparin for thromboprophylaxis in
123
9.
10.
patients receiving chemotherapy for cancer. N Engl J Med. 2012;366(7):601–9. Amer MH. Cancer-associated thrombosis: clinical presentation and survival. Cancer Manag Res. 2013;26(5):165–78. Elice F, Rodeghiero F, Falanga A, Rickles FR. Thrombosis associated with angiogenesis inhibitors. Best Pract Res Clin Haematol. 2009;22(1):115–28. Singal AK, Kamath PS, Tefferi A. Mesenteric venous thrombosis. Mayo Clin Proc. 2013;88(3):285–94. Heinrich N, Born M, Hoebert E, Verrel F, Simon A, Bode U, et al. Aortobifemoral embolism in an 18-year-old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma. Vasa. 2010;39:271–3. Hoton KM, Fishman EK. Multi-detector row CT of mesenteric ischemia: can it be done? Radiographics. 2001;21:1463–73. Wiesner W, Khurana B, Ji H, Ros PR. CT of acute bowel ischemia. Radiology. 2003;226:635–50. Sugden EM, Griffiths CL, Greywoode GI, Lewis SM. Acute abdomen during adjuvant chemotherapy: superior mesenteric artery thrombosis associated with CMF chemotherapy. Clin Oncol (R Coll Radiol). 2001;13(6):441–3. Allerton R. Acute mesenteric ischaemia associated with 5-FU, cisplatin and vincristine chemotherapy. Clin Oncol (R Coll Radiol). 1996;8(2):116–7.
