Acute superior mesenteric venous thrombosis: transcatheter thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery in eight patients.

Cardiovasc Intervent Radiol DOI 10.1007/s00270-014-0896-z

CLINICAL INVESTIGATION

Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients Shuofei Yang • Baochen Liu • Weiwei Ding • Changsheng He • Xingjiang Wu • Jieshou Li

Received: 15 October 2013 / Accepted: 24 March 2014 Ó Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2014

Abstract Purpose To assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV?SMA) for acute superior mesenteric venous thrombosis (ASMVT). Methods This retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described. Results Technical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7

S. Yang B. Liu W. Ding C. He X. Wu (&) J. Li Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu, People’s Republic of China e-mail: [email protected]

(6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months. Conclusions Catheter-directed thrombolytic and aspiration therapy via SMV?SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome. Keywords Acute superior mesenteric vein thrombosis Acute mesenteric ischemia Transcatheter thrombolytic therapy Combined route of mesenteric artery and vein

S. Yang e-mail: [email protected]

Introduction

B. Liu e-mail: [email protected]

Acute superior mesenteric venous thrombosis (ASMVT) is a relatively rare but insidious and potentially lethal abdominal disease. It approximately accounts for 6–9 % of acute mesenteric ischemia, 0.002–0.06 % of inpatient admissions, 0.01 % of emergency surgical admissions, and 0.1 % of laparotomies for acute abdomen [14, 31]. During the past 10 years, increase of incidence worldwide may be due to the extensive use of high-resolution, contrast-enhanced CT

W. Ding e-mail: [email protected] C. He e-mail: [email protected] J. Li e-mail: [email protected]

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S. Yang et al.: Thrombolysis by Combined Approach for Mesenteric Venous Thrombosis

venography, which facilitates early diagnosis with a sensitivity of 90 % [3, 24]. In Sweden, incidence has increased from 2.0 per 100,000 patient-years between 1970 and 1982 to 2.7 per 100,000 patient-years between 2000 and 2006 [2]. As the overall mortality is still as high as 13–50 % with traditional anticoagulation and bowel resection, the management of ASMVT remains a great clinical challenge [1, 30]. In the literature, mortality has ranged from 29 to 38 % for surgical treatment and from 13 to 19 % for nonoperative management [7]. Systemic anticoagulation is of limited value, still associated with 25 % of extrahepatic portal vein hypertension and 18 % transmural bowel infarction, and elevated risk of bleeding [5, 39]. Recently, catheterdirected thrombolysis combined with local anticoagulation and endovascular thrombectomy has been proposed as a minimally invasive treatment option offering the ability to dissolve thrombus and improve SMV flow rapidly with inspiring outcome, by percutaneous transhepatic and transjugular intrahepatic routes directly or via superior mesenteric artery approach indirectly [11, 26, 38]. It is unknown whether transcatheter thrombolytic therapy by combined route of superior mesenteric vein and artery (SMV?SMA) could enhance the effectiveness and reduce the complication. The objective of this retrospective study was to evaluate the feasibility, effectiveness, and safety of catheter-directed thrombolytic therapy by SMV?SMA for ASMVT patients with severe symptoms or deteriorating clinical condition despite systemic anticoagulation.

Materials and Methods The study was approved by the Institutional Review Board of Jinling hospital. The potential risks and benefits of the procedure were explained, and informed consent was obtained from each patient and relatives. The data were gathered from review of medical records and information was coded and entered into a database. Patient Groups and Study Design In this retrospective study, eight patients of acute or subacute (symptoms less than 30 days) superior mesenteric venous thrombosis with severe symptoms or deteriorating clinical conditions despite systemic anticoagulation that were treated by transcatheter thrombolytic therapy via SMV?SMA between May 12, 2011 and July 30, 2012 were identified. The follow-up period was from the discharge to August 31, 2013. The mean interval from symptoms to hospitalization at our hospital was 9–20 (12.63 ± 3.62) days. The demographics of the study

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population, etiology, risk factors, morbidity, mortality, and follow-up survey were assessed. The study population consisted of five male patients and three female patients with an average age of 27–60 (42.88 ± 10.92) years. Presenting symptoms included abdominal pain (n = 8), distention (n = 5), ascites (n = 4), lumbodorsal pain (n = 3), peritonitis (n = 3), constipation (n = 1), fever (n = 1), diarrhea (n = 1), nausea (n = 1), emesis (n = 1), hematemesis (n = 1), and hematochezia (n = 1; Table 1). Anatomic and imaging information about the extent and location of thrombus at diagnosis and degree of thrombus lysis at completion of transcatheter thrombolysis and before discharge were described (Table 2). The medical record, including medical and surgical history, family history, and pertinent laboratory parameters, was reviewed. History of the patients included splenectomy (n = 1), bowel resection and anastomosis (n = 2), alcohol abuse (n = 3), cirrhosis (n = 2), hamartoma of kidney (n = 1), deep vein thrombosis (n = 1), and hysterectomy with bilateral salpingo-oophorectomy for myoma (n = 1; Table 1). Diagnosis and Evaluation Five patients were diagnosed at local hospital and the other three at our institute by CT venography of portal phase. After admission, all patients received transcatheter direct and indirect portography before thrombolysis treatment (Figs. 1, 2). Plasma values were detected for blood routine examination including white blood cell (WBC), red blood cell (RBC), platelet (PLT), and neutrophilic granulocyte counts, hemoglobin, C-reactive protein, serum lactate and procalcitonin levels, and hepatic and renal function, including amylase, lipase, aminotransferase, urea, creatinine, and phosphocreatine kinase levels. Coagulation was monitored by thrombin time, activated partial thromboplastin times, international normalized ratio, fibrinogen, antithrombin III level, and thromboelastogram every 24 h throughout hospitalization. All patients were screened for deficiency of protein C or S, Factor V Leiden syndrome, and prothrombin gene mutation (Table 1). Technical success was evaluated by transcatheter portography and CT venography at the conclusion of therapy, defined as restoration of flow in the main SMV with filling to SMV branches. Minor complications were identified as temporary and self-limiting symptoms without any clinical sequelae, such as pain or bleeding at the puncture site and transient limb numbness or swelling. Major complications were those that required further therapy, an unplanned increase in the level of care, prolonged hospitalization ([48 h), or resulted in permanent adverse sequelae and death, including catastrophic haemorrhage requiring transfusion, shock, sepsis, and secondary pulmonary

S. Yang et al.: Thrombolysis by Combined Approach for Mesenteric Venous Thrombosis Table 1 Patient demographics, presenting symptoms, etiologies, and disease courses No. of patients

Age (year)/ gender

Initial symptoms and signs

Etiologies and risk factors

Indication for intervention

Symptoms to admission at local hospital (day)

Symptoms to admission at our hospital (day)

Symptoms to intervention (day)

Length of hospital stay (day)

1

29/F

Constipation, distention, abdominal pain, ascites, dysphoria

Deficiency of protein S, postcesarean for 18 days, inferior vena cava filter implantation

Worsening pain, despite Anticoagulation

3

10

12

20

2

40/M

Abdominal pain, distention, lumbodorsal pain, ascites

Cirrhosis, hepatitis B, splenectomy

Continued pain, distension, no change on CT, despite Anticoagulation

4

10

13

10

3

60/M

Abdominal pain, lumbodorsal pain, nausea, emesis

Cirrhosis caused by schistosomiasis, hamartoma of kidney, bowel resection, and anastomosis 7 days ago

Continued pain, distension, despite anticoagulation

5

12

16

19

4

44/F

Abdominal pain, lumbodorsal pain, fever

Hysterectomy with bilateral salpingo-oophorectomy for myoma of uterus 15 days ago

Increasing severity of symptoms despite Anticoagulation

3

15

19

16

5

47/F

Abdominal pain, hematemesis, hematochezia

Antiphospholipid syndrome, bowel resection and anastomosis 5 days ago

Severity of symptoms despite Anticoagulation

2

9

10

19

6

27/M

Distention, abdominal pain, ascites, peritonitis

Deficiency of protein C, alcohol abuse, lower extremity deep vein thrombosis 8 years ago

Progression of pain despite Anticoagulation

5

14

14

22

7

45/M

Abdominal pain, distention, diarrhea, fever, ascites, peritonitis

Alcohol abuse, long-term fixed

Continued pain, despite anticoagulation, no change on CT

6

20

20

21

8

51/M

Abdominal pain, distention, peritonitis

Alcohol abuse, acute pancreatitis

Worsening pain and distension despite anticoagulation

4

11

14

27

embolism. Short-term outcome were measured by 30-day survival rate, improvement of abdominal pain, need for exploratory surgery, and ability to tolerate enteral nutrition or oral nutrition intake during hospitalization. Long-term outcome was assessed by survival rate and recurrence of SMV thrombosis in subsequent outpatient visits or hospitalization. Degree of thrombus lysis was divided into three levels: no lysis, partial lysis, or complete lysis. No lysis was defined as thrombus removal of less than 50 % or even worsening. Partial lysis meant 50–90 % clot removal. Complete lysis represented greater than 90 % clot removal. The degree of lysis in each case was determined with

imaging studies, primarily digital subtraction angiography (DSA) portography and CT venography by two interventionalist and radiologists independently (Table 2). Supportive Management On admission, five patients had worsening abdominal pain despite systemic anticoagulation by low molecular heparin at local hospital. The others patients were initially infused with fondaparinux sodium (Glaxo SmithKline, Greenford, UK) 5 mg/day and argatroban (TIPR Pharmaceutical Responsible Co., Ltd, Tianjing, China) 80 ml/day intravenously for anticoagulation at our hospital. To all patients,

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Location of thrombosis

IVC?SMV?PV

SMV

SMV

SMV?PV?SV

SMV?PV?SV

SMV?PV

SMV?PV

No. of patients

1

123

2

3

4

5

6

7

90–95 %

95–100 %

90–95 %

85–95 %

80–90 %

85–90 %

85–95 %

Extent of thrombosis (of diameter)

PT?SMA

TI?SMA

PT?SMA

PT?SMA

TI?SMA

TI?SMA

PT?SMA

Route of thrombolysis

Multiple sidehole infusion catheter







Catheter

Table 2 Transcatheter thrombolysis and clinical outcome

Success

Success

Success

Success

success

Success

Failure to TI/ success to PT and SMA

Technical operation

7

6

7

5

6

Urokinase (200,000 IU/ day), fondaparinux sodium (5 mg/day), argatroban (20 ml/ day), pavarin (120 mg/day)







6

5

Agent and dose of SMA thrombolysis

Length of SMA thrombolysis

14

15

10

13

12

7

12

Length of SMV thrombolysis

Urokinase (200,000 IU/ day), fondaparinux sodium (5 mg/ day), argatroban (20 ml/day)







Agent and dose of SMV thrombolysis

4,200,000

6,300,000

4,250,000

4,500,000

5,400,000

Partial (80–85 %)

Partial (75–80 %)

Partial (80–85 %)

Partial (85–90 %)

Partial (80–85 %)

Partial (80–85 %)

Partial (70–80 %)

5,400,000

3,100,000

Thrombus lysis after thrombolysis

Total UK dose (IU)

Partial (85–90 %)

Complete (90–95 %)

Aspiration thrombectomy




Aspiration thrombectomy and balloon venoplasty


Aspiration thrombectomy and balloon venoplasty



Partial (80–90 %)



Thrombus lysis before discharge

Endovascular mechanical manipulation


IVC inferior vena cave, SMV superior mesenteric vein, PV portal vein, SV splenic vein, PT percutaneous transhepatic route, TI transjugular intrahepatic route, SMA superior mesenteric arterial route

Partial (85–90 %) Aspiration thrombectomy Partial (75–80 %) 6,000,000 13 IVC?SMV?PV 8

95–100 %

PT?SMA


Success

7



Thrombus lysis before discharge Endovascular mechanical manipulation Thrombus lysis after thrombolysis Length of SMV thrombolysis Location of thrombosis No. of patients

Table 2 continued

Extent of thrombosis (of diameter)

Route of thrombolysis

Catheter

Technical operation

Length of SMA thrombolysis

Agent and dose of SMA thrombolysis

Agent and dose of SMV thrombolysis

Total UK dose (IU)


nasogastric suction was applied to diminish the bowel movements as well as intraluminal pressure. Broad-spectrum prophylactic antibiotics were administered. Fluid, electrolyte, and acid-base balance were adequately taken care of. Dextran was used to improve microcirculation in addition to volume expansion. Vasopressors and somatostatin were never used to avoid exacerbating intestinal circulatory compromise. Thrombolytic Procedure Indications and Contradictions At our institute, the catheter-directed thrombolysis was indicated for extensive ASMVT with severe symptoms and persistent or worsening abdominal pain despite systemic anticoagulation. For patients with moderate and localized peritonitis, although bowel infarction was suspected, catheter-directed thrombolysis was a preferential alternative rather than emergent laparotomy if patient’s general condition permitted. The contraindication contained the evidences of bowel infarction or perforation and previous stroke, primary or metastatic central nervous system malignancies, an active bleeding diathesis, and recent gastrointestinal bleeding. Direct transcatheter thrombolysis was not recommended on unfavorable anatomy of the portal vein, marked atrophy of the liver, or portal venous cavernous transformation (Table 3). SMA and SMV Catheterization The route, thrombolytic agent, catheter type, length of treatment, other interventional techniques, and complications were reviewed for each patient. Choice between direct transcatheter thrombolysis by percutaneous transhepatic or transjugular intrahepatic routes was determined by discussion of interventionalists, radiologists, and gastrointestinal surgeon according to patient’s CT image, vascular, and general conditions. A puncture of the right common femoral artery according to the Seldinger technique and implantation of the 5-Fr sheath (Cordis, Miami, FL) was performed. Selective catheterization of the SMA with 5-Fr multiple side-hole infusion catheter (AngioDynamics, Queensbury, NY) was done. Then the transjugular intrahepatic or percutaneous transhepatic approach was attempted. The portal system was studied with indirect portography obtained during the venous phase following iodinated contrast medium injections into the SMA and the splenic artery. The ultrasonography and fluoroscopic guidance were used for the portal vein puncture. Following infiltration of local anesthesia, a Rosch-Uchida Transjugular Liver Access set (Cook, Bloomington, IN) was used to gain access to the

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portal vein branch from transjugular approach. Once the catheter was placed inside a portal branch, the thrombus of the SMV could be traversed with the aid of a 5-Fr Cobra catheter (Cordis, Miami, FL) and a 0.035-inch hydrophilic guidewire (Terumo, Japan). After reaching distal branches of the SMV, the Cobra catheter was exchanged for an 6–8 mm diameter angioplasty balloon catheter (Bard, Tempe, AZ) to open a channel, and then the 10-Fr RoschUchida sheath was put into the portal vein. Percutaneous transhepatic access to the portal vein was achieved with a 14-gauge trocar needle (Cook). Transhepatic access was achieved aiming to the right portal vein via the right midaxillary line subcostally under ultrasonography guidance. With transhepatic access secured with a 6-Fr sheath (Cordis), direct mesenteric and portal venography was performed. Through the 10-Fr sheath, an angled 8-Fr guiding catheter (Cordis) was used to aspirate as much of the thrombus as possible from the SMV with a Luer-Lok 60-ml syringe. The aspiration procedure was performed from distal to proximal clots in 10–15 cycles. Then, a 5-Fr multiple side-hole infusion catheter was securely placed within the thrombosed SMV. Any stenosis after thrombolysis was treated with balloon venoplasty with PTA balloon dilation catheter (Bard). No stents were used. Agents Infusion Thrombolysis via SMA was started with a bolus injection of 100,000 IU of urokinase (Nanjing Nanda Pharmaceutical Co., Ltd, Nanjing, China) followed by continuous infusion 200,000–300,000 IU/day. Catheter-directed local anticoagulation with fondaparinux sodium 5 mg/day plus argatroban 80 ml/day and arteriospasm remission with pavarin (Northeast Pharmaceutical Group Shenyang No. 1 Pharmaceutical Co., Ltd, Shenyang, China) 120 mg/day were continuously administered into SMA as well. With infusion catheter established in SMV, a bolus of 100,000 IU urokinase was injected using a hand-pulse spray technique. Following the mechanical aspiration procedure, continuous thrombolytic and local anticoagulation therapy was started with urokinase 200,000–300,000 IU/day and fondaparinux sodium 5 mg/day plus argatroban 40 ml/day. Evaluation and Termination of Thrombolysis Ultrasonography assessment of PV and SMV patency was performed at 24, 48, 72 h, and 1 week following the procedure and before discharge. SMA arteriography was performed 24 h postcatheterization and before catheter removal to show recanalization of the portal vein trunk and tertiary venous arcades of jejunal and ileal branches. Direct portography was performed in each patient before catheter

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removal. Contrast-enhanced CT scan was applied at completion of thrombolytic therapy. Termination of treatment was based on clinical and radiographic findings. After treatment, the catheters were removed and the sheaths were removed within 24 h. The SMA catheter was removed in 7 days and SMV catheter could be retained to 15 days. After removal of a transhepatic catheter, the tract was embolized with NesterÒ Embolization Coil (Cook, Bloomington, IN). At the completion of transcatheter thrombolysis, intravenous administration of fondaparinux sodium 5 mg/day was reinitiated and followed by long-time anticoagulation with warfarin (Jiufu Pharmaceutical Co., Ltd., Shanghai, China) as soon as enteral nutrition or oral nutrition intake was fully tolerated, adjusted to maintain an International Normalized Ratio of 2–3. The duration of anticoagulation is approximately 6 months for patients with known reversible factors but lifelong for patients who are idiopathetic or with prothrombotic states. Study Endpoints Records of hospitalization and clinic visits were reviewed from the time of discharge until August 31, 2013. Endpoints of this study were defined as death, lost to follow-up, and most recent hospital or clinic visit. Follow-Up All patients had clinical and imaging follow-up at first month then every 2 months in first half year and every 3 months afterwards. During the follow-up, all patients were evaluated by clinical symptoms and signs, laboratory tests of blood routine examination, hepatic and renal function and coagulation, contrast-enhanced CT and ultrasonography of portal vein, and SMV. Six-month and 1-year mortality and recurrence rate were assessed.

Results Technical Success Technical success was achieved with substantial improvement in symptoms and clot resolution after thrombolytic therapy in all eight patients with no death. Five patients received SMV transcatheter thrombolysis by percutaneous transhepatic and three by transjugular intrahepatic route. Patient 1 had a failed transjugular intrahepatic puncture and was treated with a transhepatic approach. The eight patients were discharged 5–10 (7.6 ± 2.0) days after admission. Mean procedural time was 69–85 (76.5 ± 7.58) min. Local urokinase injection and manual aspiration


Fig. 1 Patient 3: 60-year-old man with splenomegaly, schistosomiasis cirrhosis had abdominal pain, lumbodorsal pain, nausea, emesis for 5 days. He had undergone bowel resection and anastomosis 1 week previously for ileus. A, B Selected coronal and axial image from admission contrast-enhanced CT show thrombus (white arrow) within the SMV with bowel edema and mesenteric thickening. C Prethrombolysis direct venography via transjugular intrahepatic approach to the portal vein shows extensive thrombosis of the SMV trunk and branches (black arrow). D, E Pretreatment digital subtraction SMA angiogram shows patent SMA and delayed venous phase demonstrates the portal vein faintly opacified with filling defect, no visualization of the SMV, and remarkable pooling of

contrast medium at the small intestine. F, G CT image at the same level as A, B obtained after thrombolytic therapy shows the wide patent SMV (white arrow) with hardly any residual wall thrombus. H Direct portal venography via the infusion catheter (black arrow), obtained 6 day after the catheter infusion of thrombolytics by SMA?SMV, shows patent PV and passable SMV with residual wall thrombus (white arrow). SMA catheter was removed and SMV catheter was kept for another 6 days. I, J Six days after SMA?SMV catheter-directed urokinase infusion, at the same phase as the SMA angiogram as in D, E shows improved visualization of the portal vein (arrows) as well as the primary, secondary, and tertiary branches of the SMV. Note the infusion catheter within the SMA

thrombectomy of the SMVT resulted in partial restoration of blood flow in the main SMV, which was documented on immediate direct SMV venography. Continuous thrombolytic therapy via indwelling catheter in the SMA was performed for 5–7 (6.13 ± 0.83) days. The SMV transcatheter thrombolysis lasted for 7–15 (12 ± 2.51) days. At completion of the SMV urokinase infusion, significantly improved filling of the SMV was seen in all eight patients, which was confirmed by repeated venography via the infusion catheter. Contrast-enhanced CT images obtained before discharge demonstrated that nearly complete lysis of SMV thrombosis in all patients, with improvement in edema of the intestine and mesentery in all patients (Table 2; Figs. 1, 2).

distention and further surgery was applied. The 30-day mortality was 0 %.

Clinical Improvement Sufficient clinical improvement, characterized by progressive decrease in abdominal pain and distention, was seen in all patients after 24–48 h of urokinase infusion. Four patients continued to improve clinically during the thrombolytic therapy via the indwelling infusion catheter in the SMA?SMV. Oral nutrition intake or enteral nutrition was started at 3–6 (4.13 ± 1.13) days after abdominal pain, nausea, distention, and diarrhea was completely resolved. The other four patients regained localized abdominal

Further Surgery and Complications In our series, 4 (50 %) patients required further surgery after thrombolytic therapy due to regain of unremitting abdominal distention. Two patients received laparoscopic exploration before laparotomy, exhibiting circumscribed mesenteric thickening and bowel blackening, contracture, and adhesion. Delayed localized bowel resection of 1–2 (1.63 ± 0.48) meters was applied in all patients. Primary anastomosis was implemented in one patient with jejunostomy plus ileostomy for the other three patients. Open abdomen technique was applied in two septic patients with high risk of postoperative abdominal compartment syndrome and SMVT recurrence (Fig. 3). Minor bleeding at both the arterial and venous puncture site were observed in two (25 %) patients, but the thrombolytic therapy was not interrupted (Table 4). Follow-Up The average length of time of follow-up was 12.13 (range 10–13) months. During the follow-up period, three patients with further surgery underwent stoma reversion after 4–6

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Fig. 2 Patient 8: 51-year-old man with abdominal pain, distention, peritonitis for 4 days. A, B Selected coronal and axial image from admission contrast-enhanced CT show thrombus located in the SMV trunk and branches and the junction of portal and splenic vein (white arrow) with bowel edema, mesenteric thickening and pneumatosis cystoides intestinal loops (black arrow). C Prethrombolysis direct venography via percutaneous transhepatic approach to the portal vein shows extensive thrombosis of the SMV trunk and branches (black

arrow). D, E CT image at the same level as A, B obtained after thrombolytic therapy shows the patent SMV (white arrow) some residual wall thrombi. F Direct portal venography via the infusion catheter, obtained 7 days after the transcatheter thrombolysis via SMA?SMV, shows patent PV and SMV with local stenosis (black arrow) treated with balloon venoplasty by PTA balloon dilation catheter. SMA catheter was removed and SMV catheter was kept for another 6 days

(4.67 ± 1.15) months of enteral nutrition support at local hospital. All patients persisted asymptomatic and the 6-month and 1-year mortality were 0 % with no episodes of the SMV thrombosis recurrence. Warfarin was applied orally in all patients at least 6 (range 6–13) months after discharge. During the 1st, 4th, 6th, and 12th month of follow-up, ultrasonography and contrast-enhanced CT confirmed the patency of the SMV (Table 4). There was limited clinical information available regarding evidence for the development of portal hypertension during followup.

gene mutation [19, 32]. Local factors are associated with initial thrombus formation in the large veins whereas hypercoagulability leads to thrombosis beginning in the intramural venules, vasa recta, and venous arcades [14]. Differences in the initial location and propagation of thrombus are correlated with distinctness in bowel infarction rate. Underlying causes are identified in approximately 75 % of patients by laboratory evaluation for hypercoagulable parameters [19]; 56 % of them are in identifiable hypercoagulable state [29]. Other predisposing factors include myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, abdominal infection, portal hypertension, malignancies, and using anticonceptive [4, 10, 21]. In our series, all patients had etiological and risky factors, including splenectomy in one, cirrhosis in two, deficiency of serum protein S/C in two, antiphospholipid antibody syndrome in one, and other abdomen inflammatory causes in four patients. Transcatheter thrombolytic therapy for ASMVT results in rapid recanalization of the SMV, resolution of symptoms, and early resumption of enteral nutrition, with direct

Discussion The exact etiology and natural pathophysiological course of ASMVT remain unclear. Different pathophysiologic mechanisms have been postulated as local factors and systemic hypercoagulable states, such as deficiencies of antithrombin III, protein C or protein S, Leiden syndrome, antiphospholipid antibody syndrome, and prothrombin

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S. Yang et al.: Thrombolysis by Combined Approach for Mesenteric Venous Thrombosis Table 3 Indications and contradictions of intracatheter thrombolysis of ASMVT by the combined route Indications

Contraindications

1. Acute superior mesenteric venous thrombosis with symptoms of less than 3 weeks

1. Definite evidences of bowel infarction or perforation

2. Extensive superior mesenteric venous thrombosis of peripheral (thrombosis in the branches and venous arcades of superior mesenteric vein) or mixed (thrombosis both in the main trunk and branches of superior mesenteric vein) type

2. Unfavorable anatomy (such as complete thrombosed portal vein, or portal venous cavernous transformation, and marked atrophy of the liver)

3. Severe symptoms or persistent symptoms or worsening of abdominal pain despite anticoagulation

3. Coagulation disorders 4. Hepatic and renal failure, malignancies or other serious systemic illness at admission 5. Allergy to contrast medium, anticoagulant or thrombolytic agents 6. Massive intracranial or gastrointestinal hemorrhage in recent 3 months 7. Severe trauma in recent 4 weeks 8. Pregnancy 9. Uncontrolled hypertension (systolic pressure [ 180 mmHg, diastolic pressure [ 110 mmHg) 10. Age of patients less than 18 or older than 80 years

Fig. 3 Further surgery after transcatheter thrombolysis (continuation of Patient 8 in Fig. 2). A, B During delayed operation after transcatheter thrombolysis, circumscribed mesenteric thickening and bowel blackening, bleeding, contracture, and adhesion were observed

and localized bowel resection was applied. C Jejunostomy plus ileostomy with open abdomen was performed in septic patients with high risk of postoperative abdominal compartment syndrome and SMVT recurrence

access to additional endovascular mechanical therapies. Percutaneous transhepatic access is technically easier under guidance of ultrasound or X-ray and prone to remove larger thrombus within the trunk of the SMV [18, 40]. It allows multiple maneuver of mechanical devices compared with transjugular intrahepatic access [21, 34]. Since this route traverses the hepatic capsule and is followed by thrombolysis and anticoagulation, postinterventional embolization of the tract is required because of high risk of intraperitoneal or subcapsular hepatic hemorrhage [12, 26, 34]. For patients with ascites or coagulation disorder, transjugular intrahepatic approach is recommended [11,

39]. Without traversing the hepatic capsule, it is safer in patients with thrombolysis and anticoagulation than percutaneous transhepatic access [33]. Additional therapies, such as venoplasty and stent placement for elastic recoil or stenosis, are possible by this route [37]. However, the technical difficulty and potential hepatic function injury are main drawbacks and intra-abdominal bleeding is still a potential serious complication of this approach [6, 39]. Indirect thrombolytic therapy via SMA is technically simpler and beneficial to infuse thrombolytic agents into small mesenteric venous branches, which enable dissolution of thrombi within capillaries and venules [28, 38].

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S. Yang et al.: Thrombolysis by Combined Approach for Mesenteric Venous Thrombosis Table 4 Complications and follow-up No. of patients

Clinical outcome

Complications

Further surgery

Length of follow-up (mo)

Follow-up results

1

Clinical improvement

Sepsis

Bowel resection of 1.5 m with jejunostomy and ileostomy

10

No recurrence

2

Elimination of symptoms

None

None

12

No recurrence

3


Bleeding and flare at puncture site, fever

None

13

No recurrence

4


None

None

12

No recurrence

5


Flare at puncture site, fever

None

13

No recurrence

6


None

Laparoscopic exploration, bowel resection of 1.0 m and primary anastomosis

13

No recurrence

7


None

Bowel resection of 2.0 m with jejunostomy and ileostomy, open abdomen, intraoperative venous thrombectomy

12

No recurrence

8


Sepsis

Laparoscopic exploration, bowel resection of 2.0 m with intraoperative venous thrombectomy, jejunostomy and ileostomy, open abdomen

12

No recurrence

Moreover, pavarin infusion into SMA to relieve the mesenteric arteriospasm secondary to venous engorgement, which is an important cause to irreversible bowel infarction, may reverse extensive intestinal ischemia [31]. However, this approach may result in lytic agents diverting through patent branches and collaterals and possible prolongation of the total infusion time which may increase the risk of bleeding [17, 20]. To the best of our knowledge, this is the first study to highlight the effectiveness and safety of catheter-directed thrombolysis treatment to ASMVT via SMV?SMA with favourable outcome. The combined route was even mentioned in the studies by Hollingshead et al. [17] and Hechelhammer et al. [15]. Since most ASMVT in clinic is both in SMV trunk and branch venules caused by thrombophilic condition plus abdominal local inflammatory factors, thrombolysis via SMV?SMA is significantly efficient in cleaning up all the thrombus and reestablishment of antegrade flow, even incomplete, to allow additional time for thrombolytics and anticoagulation therapy [4, 9, 22]. In our study, there were few bleeding complications, which we attribute to relatively low doses of thrombolytic agent and enhanced coagulation monitoring by thromboelastogram. Due to the remarkably low body weight, different individual constitution and physical condition of Chinese people, the routine dosage of urokinase for Chinese patient is 200,000–800,000 IU/day according to the Chinese guideline of thrombolysis treatment and our experience, significantly lower than European or American people. In our series, the SMA catheter was removed in a

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week due to the potential risk of catheter-related infections and thrombosis or embolization in the SMA branches or femoral artery near the arteriotomy site during prolonged catheterization [35]. Generally, systemic anticoagulation with supportive care comprises the initial treatment in patients without evidence of bowel infarction or perforation. Emergent laparotomy is imperative with evidences of transmural bowel infarction and peritonitis despite surgical difficulty and high risk of rethrombosis in demand of ‘‘second-look laparotomy’’ within 24–48 h [5, 7, 13, 23]. At present, early detection and medical treatment obviating surgical intervention became feasible. In this study, transcatheter thrombolysis instead of emergent laparotomy was implemented to two patients with moderate local peritonitis that anticoagulation was ineffective. Bowel ischemia was assessed directly by laparoscopic examination after initiation of thrombolytic therapy. With symptoms removal, delayed localized bowel resection was operated for these two patients with primary anastomosis for one. This treatment modality succeeds in avoiding risk of short-bowel syndrome due to extensive bowel resection and unnecessary laparotomy, which could cause extra and repeated strikes to ASMVT patients of critical illness. Further studies are warranted to confirm whether interventional therapy with delayed surgery benefits all patients of mild localized peritonitis under permission of general condition. Techniques of mechanical thrombectomy, including mechanical thrombectomy, stent implantation, angioplasty,


transjugular intrahepatic portosystemic shunt creation, and suction thrombectomy, have evolved as an important part of thrombolysis, which were able to augment the ability to rapid thrombus remove and recanalization with shortened thrombolytic therapy [25, 27, 34]. However, complicated endovascular manipulations add risk of acute trauma to vessel wall promoting thrombus reformation and bleeding [36]. Aspiration thrombectomy is applied to clear the thrombus burden in our series due to its minor injury and little intrahepatic portal thromboembolization. It has been recognized that these methods could be more effective when there is a structural reason for acute thrombus [8, 16, 36]. Continued study is warranted for more comprehensive evaluation. There are several limitations of this study, including the retrospective cohort design of small sample size without control group, randomization and lack of long-term followup, and the uniformity of evaluation and treatment. An inherent selection bias is inevitable, because only those patients in whom anticoagulation has failed or who exhibited severity of symptoms dictating more aggressive management would have been treated with catheter-directed thrombolysis. Therefore, no statistically significant results could be drawn regarding route, agent, or dose of thrombolytic therapy and underlying risk factors. No treatment protocols at our institution or international guidelines or consensus for ASMVT exist currently. Nevertheless, by reason of low incidence as well as constant evolution of therapeutic techniques, it is hard to conduct a large-scale, randomized, controlled trial. We will continue the follow-up to assess the long-term outcome of this method, and a prospective clinical investigation of larger sample size has been prepared at our institute.

Conclusions Transcatheter thrombus aspiration and local thrombolytic therapy by combined route of superior mesenteric vein and artery in addition to anticoagulation is feasible and appears to be an effective and safe treatment for symptomatic ASMVT. It can be applied for patients in whom conservative management with anticoagulation alone fails and whose clinical condition warrants intervention treatment. This method is beneficial in avoiding patient death, resolving thrombus, improving symptoms rapidly, and avoiding bowel resection for patients without peritonitis and reversing extensive intestinal ischemia, localizing infarcted bowel segment, and preventing short-bowel syndrome for patients with mild localized peritonitis and suspected bowel gangrene. Further evaluation of these techniques and outcomes should continue to be pursued.

Conflict of interest Shuofei Yang, Baochen Liu, Weiwei Ding, Changsheng He, Xingjiang Wu, and Jieshou Li have no conflict of interest.

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Initial transcatheter thrombolysis for acute superior mesenteric venous thrombosis.

Mechanical thrombectomy-assisted thrombolysis for acute symptomatic portal and superior mesenteric venous thrombosis.

Simultaneous thrombosis of superior mesenteric artery and superior mesenteric vein following chemotherapy: MDCT findings.

Combination of Surgical Thrombectomy and Direct Thrombolysis in Acute Abdomen with Portal and Superior Mesenteric Vein Thrombosis.

Percutaneous Mechanical Thrombectomy Treatment of Acute Superior Mesenteric Artery Embolism.

Acute mesenteric ischemia caused by isolated superior mesenteric artery dissection.

Traumatic superior mesenteric artery--portal vein fistula.

Massive superior mesenteric venous aneurysm with portal venous thrombosis.

Suppurative duodenitis and superior mesenteric vein thrombosis after toothpick ingestion.

Superior mesenteric artery syndrome.

[CT diagnosis in idiopathic thrombosis of the superior mesenteric vein].

Aspiration therapy for acute superior mesenteric artery embolism with an angled guiding sheath and guiding catheter.

Superior mesenteric artery syndrome.

Acute superior mesenteric artery occlusion complicated by basilar artery occlusion.

Superior Mesenteric Vein Thrombosis Associated with Hormonal Contraceptive Use.

Superior mesenteric artery thrombosis after abrupt discontinuation of rivaroxaban.

Infected Superior Mesenteric Artery Aneurysm.

Familial superior mesenteric artery syndrome.

Superior mesenteric artery thrombosis associated with antiphospholipid syndrome.

Hybrid technique to treat superior mesenteric artery occlusion in patients with acute mesenteric ischemia.

Postpancreatoduodenectomy Hemorrhage Treated by Combined Transcatheter Arterial Embolization and Superior Mesenteric Artery to Iliac Artery Bypass: Report of a Case.

Acute abdomen resulting from concurrent thrombosis of celiac trunk and superior mesenteric artery.

Mesenteric castleman disease mimicking superior mesenteric artery aneurysm.

Isolated superior mesenteric artery dissection in China.