# Therapeutic Anticoagulant Does not Modify  Thromboses  Rate Vein after Venous Reconstruction  Following Pancreaticoduodenectomy

Authors: Mehdi Ouaïssi; Igor Sielezneff; Nicolas Pirro; Rémi Bon Mardion; Jean Batiste Chaix; Abdelrhame Merad; Stéphane Berdah; Vincent Moutardier; Silvia Cresti; Olivier Emungania; Loundou Anderson; Brunet Christian; Sastre Bernard
Journal: Gastroenterology Research and Practice
 (2008)

---

## Abstract

Recommendations for anticoagulation following major venous
reconstruction for pancreatic adenocarcinoma (PA) are not clearly
established. The aim of our study was to find out the relation
between postoperative anticoagulant treatment and thrombosis rate
after portal venous resection.Materials and methods. Between 1986
and  2006, twenty seven portal vein resections were performed
associated with pancreaticoduodenectomies (n=27) (PD).We defined
four types of venous resection: type I was performed 1 cm above
the confluent of the superior mesenteric vein (SMV) (n=12); type
II  lateral resection and venorrhaphy at the level of the
confluent SMV (n=12); type III (n=1) resulted from a primary
end-to-end anastomosis above confluent and PTFE graph was used for
reconstruction for type IV (n=2). Curative anticoagulant treatment
was always indicated after type IV (n=2) resection, and after
resection of type II when the length of venous resection was
longer than ≥2 cm. Results. Venous thrombosis rate reached: 0%,
41%, and 100% for type I, II, IV resections, respectively. Among
them four patients received curative anticoagulant treatment.
Conclusion. After a portal vein resection was achieved in the
course of a PD, curative postoperative anticoagulation does not
prevent efficiently the onset of thrombosis.


---

## Body

## 1. Introduction

Resection of pancreatic duct adenocarcinoma  has a high mortality rate
[1]. Surgery still  remains the only curative treatment, and tumoral invasion of  the portal vein is not a contraindication  of resection. Several techniques of
venous resection  and reconstruction have been  described, such as primary
lateral resection and venorrhaphy, primary  circumferential resection with end-to-end
anastomosis or graft interposition [2]. Recommendations for anticoagulation
following major venous reconstruction for malignancy are not clearly
established.The aim of our study was to find out a relation between postoperative
anticoagulant treatment and thrombosis portal rate after mesentericoportal
segmental venous resection.


## 2. Materials and Methods

From January 1996 to December 2006, 500 pancreatic  resections were
performed with curative intents in two surgical digestive departments. Twenty seven portal
vein resections were performed in the course of a pancreaticoduodenectomy (PD).
Clinicopathologic findings were analyzed to determine factors which are able to affect rates
of morbidity and thrombosis in relation with venous reconstruction and
anticoagulation treatment.


### 2.1. Operative Technique

Contrast-enhanced computed tomography has been the most useful imaging
exams to determine local respectability [3, 4]. When
adherence to the lateral or posterior wall of the portal vein was encountered,
surgeons preferred venous resection.


### 2.2. Pancreatic Resection

Dissection of retroperitoneal margin was carried out prior to the venous
resection. Aims of this technical choice were to avoid the need of venous
anastomosis prior to the removal of the specimen to limit duration of venous
occlusion and to allow as far as possible a preservation of the splenic vein.
This was done either by a large kocher manoeuvre or by isolation of the
superior mesenteric artery (SMA) both at its origin and the uncinate process. Kocher’s
manoeuvre oriented the SMA posterior to the portal vein and superior venous
mesenteric and allowed an easy access for completion of the retroperitoneal
dissection. Arterial branches coursing into the uncinate were sequentially
clamped, divided, and ligated. Complete liberation of the pancreas from the SMA
was done in the early course of the operation. The pancreatic head was then
rotated back to its normal orientation; venous resection was performed as the
final step of the resection.


### 2.3. Resection and Venous Reconstruction

Vascular control was always obtained proximally and distally taking care
to isolate the superior mesenteric vein (SMV), portal vein (PV), and splenic
vein (SV). Control of the gastric vein was sometimes required. We did not
perform SMA occlusion because the duration of the clamping period of the PV was
always less than 20 minutes. Type of resection is summarized in  Table1. A
wedge resection was performed in case of limited ingrowths; elsewhere segmental
resection was achieved when venous  ingrowths appeared to be more extensive.Table 1
Types of resection and anticoagulation treatment associated with complications (hemorrhagic, thrombosis) and mortality rates.
Preoperative treatmentType I (n=12)Type II (n=12)Type III (n=1)Type IV (n=2)Preventive anticoagulation10 (83%)8 (66%)1 (100%)0 (0%)Curative anticoagulation2 (17%)4 (34%)0 (0%)2 (100%)Median resection size (cm)1.5 (2–4)1 (1–4)34.5Thrombosis (%)0 (0%)5 (41%)0 (0%)2 (100%)Hemorrhage (%)0 (0%)3 (25%)0 (0%)1 (50%)Mortality rate (%)0 (0%)2 (16%)0 (0%)1 (50%)We defined four types of venous resection: (1) in type I, lateral
resection and venorrhaphy of portal were performed; these resections were
realized>1 cm above the SMV confluent (n=12); (2) in type II, lateral
resection and venorrhaphy of SMV and PV confluent were performed (n=12); (3) in
type III, a primary end-to-end anastomosis above the SMV and PV confluent was
performed (n=1); (4) in type IV, a circumferential resection (length >3 cm)
of the SMV and PV confluent was carried out and PTFE graph was used for
reconstruction (n=2). Reimplantation of SV was never achieved in case of type
IV resection.


### 2.4. Anticoagulant Treatment

Curative anticoagulant treatment was always indicated for type IV (n=2)
resections and in four cases (30%) of type II resections when the length of
venous resection was ≥2 cm. Curative anticoagulant was based on systemic anticoagulation therapy by heparin
systemic anticoagulation therapy by Heparin (500 unit/kg/day) was
indicated for 10 days in order to increase the activated partial thromboplastin
time to 1.5–2.0 times that of
control and then the treatment was discontinued at day 8. The oral
anticoagulation drug (with antivitamine K) was given after control CT scan at
day 8 to raise the mean international normalization ratio (INR). The rate of INR was between 2.5 and 3 and the
treatment was performed during three months. Other patients had preventive
anticoagulation by low molecular weight heparin.


### 2.5. Clinical and Radiological Follow Up

All patients benefited from angiographic CT scan on day 7. Diagnosis of
venous occlusion was settled on clinical findings (hepatic failure, fever), on
biological data showing biological hepatic tests disturbances, and on CT scan
findings. In the distant postoperative course, patients were followed
clinically and by CT scan at 3, 6, and 12 months.Post operative hospital stay and early outcome, were assessed. Surgical and/or medical complications were registered
and classified as either minor or major. Postoperative pancreatic fistula was
defined such as an international study group definition [5]. All pancreatic
fistulas were deemed to be a major surgical complication. Biliary fistula was
defined as biliary staining from drainage fluid. Pancreatic and/or biliary
fistulas were treated by octreotide and antibiotics administration, or surgery
if required. Postoperative gastric atony was defined by the need of inserting a
nasogastric tube over day 4 or as delayed oral food intake after postoperative
day 8. Mortality was defined as death occurring in the course of the hospitalization
or within 3 months after discharge.


### 2.6. Study End Point

Primary end points included postoperative survival, postoperative complications, and length of hospital stay.


### 2.7. Statistical Analysis

Statistical analyses were conducted using SPSS version 13.0.1 (SPSS Inc, Ill, USA). Association between qualitative variables was assessed with chi-square test (or Fisher exact test, as appropriate).  Means or median of continuous variables were analyzed by Student’st-test.
Results of parametric and nonparametric data were expressed as mean (±SD) and
median (±SD), respectively. All variables were dichotomized. Confidence
intervals were set at 95%. Actuarial survival was analyzed by Kaplan Meier
method and the survival difference was compared by log rang test. A value for P<.05 was considered to be statistically significant.


## 2.1. Operative Technique

Contrast-enhanced computed tomography has been the most useful imaging
exams to determine local respectability [3, 4]. When
adherence to the lateral or posterior wall of the portal vein was encountered,
surgeons preferred venous resection.


## 2.2. Pancreatic Resection

Dissection of retroperitoneal margin was carried out prior to the venous
resection. Aims of this technical choice were to avoid the need of venous
anastomosis prior to the removal of the specimen to limit duration of venous
occlusion and to allow as far as possible a preservation of the splenic vein.
This was done either by a large kocher manoeuvre or by isolation of the
superior mesenteric artery (SMA) both at its origin and the uncinate process. Kocher’s
manoeuvre oriented the SMA posterior to the portal vein and superior venous
mesenteric and allowed an easy access for completion of the retroperitoneal
dissection. Arterial branches coursing into the uncinate were sequentially
clamped, divided, and ligated. Complete liberation of the pancreas from the SMA
was done in the early course of the operation. The pancreatic head was then
rotated back to its normal orientation; venous resection was performed as the
final step of the resection.


## 2.3. Resection and Venous Reconstruction

Vascular control was always obtained proximally and distally taking care
to isolate the superior mesenteric vein (SMV), portal vein (PV), and splenic
vein (SV). Control of the gastric vein was sometimes required. We did not
perform SMA occlusion because the duration of the clamping period of the PV was
always less than 20 minutes. Type of resection is summarized in  Table1. A
wedge resection was performed in case of limited ingrowths; elsewhere segmental
resection was achieved when venous  ingrowths appeared to be more extensive.Table 1
Types of resection and anticoagulation treatment associated with complications (hemorrhagic, thrombosis) and mortality rates.
Preoperative treatmentType I (n=12)Type II (n=12)Type III (n=1)Type IV (n=2)Preventive anticoagulation10 (83%)8 (66%)1 (100%)0 (0%)Curative anticoagulation2 (17%)4 (34%)0 (0%)2 (100%)Median resection size (cm)1.5 (2–4)1 (1–4)34.5Thrombosis (%)0 (0%)5 (41%)0 (0%)2 (100%)Hemorrhage (%)0 (0%)3 (25%)0 (0%)1 (50%)Mortality rate (%)0 (0%)2 (16%)0 (0%)1 (50%)We defined four types of venous resection: (1) in type I, lateral
resection and venorrhaphy of portal were performed; these resections were
realized>1 cm above the SMV confluent (n=12); (2) in type II, lateral
resection and venorrhaphy of SMV and PV confluent were performed (n=12); (3) in
type III, a primary end-to-end anastomosis above the SMV and PV confluent was
performed (n=1); (4) in type IV, a circumferential resection (length >3 cm)
of the SMV and PV confluent was carried out and PTFE graph was used for
reconstruction (n=2). Reimplantation of SV was never achieved in case of type
IV resection.


## 2.4. Anticoagulant Treatment

Curative anticoagulant treatment was always indicated for type IV (n=2)
resections and in four cases (30%) of type II resections when the length of
venous resection was ≥2 cm. Curative anticoagulant was based on systemic anticoagulation therapy by heparin
systemic anticoagulation therapy by Heparin (500 unit/kg/day) was
indicated for 10 days in order to increase the activated partial thromboplastin
time to 1.5–2.0 times that of
control and then the treatment was discontinued at day 8. The oral
anticoagulation drug (with antivitamine K) was given after control CT scan at
day 8 to raise the mean international normalization ratio (INR). The rate of INR was between 2.5 and 3 and the
treatment was performed during three months. Other patients had preventive
anticoagulation by low molecular weight heparin.


## 2.5. Clinical and Radiological Follow Up

All patients benefited from angiographic CT scan on day 7. Diagnosis of
venous occlusion was settled on clinical findings (hepatic failure, fever), on
biological data showing biological hepatic tests disturbances, and on CT scan
findings. In the distant postoperative course, patients were followed
clinically and by CT scan at 3, 6, and 12 months.Post operative hospital stay and early outcome, were assessed. Surgical and/or medical complications were registered
and classified as either minor or major. Postoperative pancreatic fistula was
defined such as an international study group definition [5]. All pancreatic
fistulas were deemed to be a major surgical complication. Biliary fistula was
defined as biliary staining from drainage fluid. Pancreatic and/or biliary
fistulas were treated by octreotide and antibiotics administration, or surgery
if required. Postoperative gastric atony was defined by the need of inserting a
nasogastric tube over day 4 or as delayed oral food intake after postoperative
day 8. Mortality was defined as death occurring in the course of the hospitalization
or within 3 months after discharge.


## 2.6. Study End Point

Primary end points included postoperative survival, postoperative complications, and length of hospital stay.


## 2.7. Statistical Analysis

Statistical analyses were conducted using SPSS version 13.0.1 (SPSS Inc, Ill, USA). Association between qualitative variables was assessed with chi-square test (or Fisher exact test, as appropriate).  Means or median of continuous variables were analyzed by Student’st-test.
Results of parametric and nonparametric data were expressed as mean (±SD) and
median (±SD), respectively. All variables were dichotomized. Confidence
intervals were set at 95%. Actuarial survival was analyzed by Kaplan Meier
method and the survival difference was compared by log rang test. A value for P<.05 was considered to be statistically significant.


## 3. Results

Between 1996 and 2006, 27 patients underwent
portal venous resection in the course of a pancreatic resection for tumor.
There were 15 males; mean age was66±9 (45–81) years old.
Most of the patients were operated on for malignant tumors, pancreatic duct
carcinoma (n=25), and cholangiocarcinoma (n=1), and in one case only for a
pseudotumoral chronic pancreatitis (n=1). Twenty seven PDs were performed.
Preoperative risks were evaluated using the American Society Association (ASA)
score. Most of the patients were ASA I or II (n=11, n=13), others were ASA
score III (n=3). Twelve patients had preoperative endoscopic bilary derivation.Thirteen (48%) patients underwent a pylorus
preserving PD, others (52%) underwent a standard PD. Mean time of the PD
resection was400±108 minutes. Venous lateral resection was carried out using
lateral venorrhaphy in 24 patients (89%); it was localized 1 cmabove or on SMV confluent (n=24), on
the confluent (n=12).  In one case, we used  autologous venous graph for a type II resection. For
resections III and IV, primary end-to-end anastomosis, in one case, and PTFE
graft were conducted
twice. All types of resections are summarized in Table 1. Overall mortality
was 11%. Overall morbidity was 13 (48%), including 7 (26%) cases of thrombosis,
4 (14%) cases of hemorrhagic complications, and one late pancreatic fistula
successfully treated by radiological drainage. There were 5 (18%) cases of
gastric atony. Sixteen (57%) patients required blood transfusion. The length of
the hospitalization stay was 19±9 days (Table 2).Table 2
Morbidity and mortality for all patients with venous resection.
GroupPostoperative stay (days)19±9Postoperative in intensive care unit stay (days)3±4Postoperative death3 (11%)Overall number of patients with complications13 (48%)Major surgical complications8 (30%)Thrombosis rate7 (26%)Hemorrhagic rate4 (15%)Reoperation4 (15%)Minor surgical complications5 (18.5%)Gastric atony5 (18.5%)Medical morbidity1 (4%)Embolism pulmonary1 (4%)Blood transfusion16 (57%)


### 3.1. Thrombosis Complication

The most common perioperative complication was
thrombosis which occurred in 7 patients (25%). It was diagnosed on clinical
findings: all patients had fever, ascite, and mental troubles, on biological
data: hepatic biological data increased 5 times the normal level in all the
cases. CT scan was performed in 5 cases of thrombosis showing a total portal
vein occlusion. Thrombosis occurred at mean day 4 and was associated to a
hemoperitoneum in two cases. Surgical treatment consisted in thrombectomy and
drainage of the hemoperitoneum. Despite this treatment, total portal vein
thrombosis persisted and curative anticoagulation was continued for these two patients.
One of them died after another surgical control with a new thrombectomy at day
18.Three patients were successfully treated by
curative anticoagulation. After
six months, CT scan showed a persisting thrombosis implying the persistence of
anticoagulation treatment. Two patients died of venous mesenteric
infarction despite a surgical control at days 1 and 10. Among 7 cases of thrombosis, three deaths
occurred after type II (n=2) or type IV (n=1) resection. Among them four
patients received curative anticoagulant treatment. At the end of follow up,
there was no more thrombosis or occluded anastomosis than the first cast.


### 3.2. Hemorrhage Complication

Four patients had hemorrhagic complications  requiring in all cases a surgical control. A portal vein
thrombosis was associated twice with a hemorrhagic complication. Three patients
received curative anticoagulant therapy. Surgical treatment of these hemorrhages needed
lavage, drainage, and thrombectomy in case of portal thrombosis.


### 3.3. Long-Term Outcome

Mean of follow-up was23±31 months. Once the
early postoperative course wasachieved,
no more cases of portal thrombosis occurred. There was no more thrombosis or
occluded anastomosis than the first cast. Median disease-free survival was 16
months.


## 3.1. Thrombosis Complication

The most common perioperative complication was
thrombosis which occurred in 7 patients (25%). It was diagnosed on clinical
findings: all patients had fever, ascite, and mental troubles, on biological
data: hepatic biological data increased 5 times the normal level in all the
cases. CT scan was performed in 5 cases of thrombosis showing a total portal
vein occlusion. Thrombosis occurred at mean day 4 and was associated to a
hemoperitoneum in two cases. Surgical treatment consisted in thrombectomy and
drainage of the hemoperitoneum. Despite this treatment, total portal vein
thrombosis persisted and curative anticoagulation was continued for these two patients.
One of them died after another surgical control with a new thrombectomy at day
18.Three patients were successfully treated by
curative anticoagulation. After
six months, CT scan showed a persisting thrombosis implying the persistence of
anticoagulation treatment. Two patients died of venous mesenteric
infarction despite a surgical control at days 1 and 10. Among 7 cases of thrombosis, three deaths
occurred after type II (n=2) or type IV (n=1) resection. Among them four
patients received curative anticoagulant treatment. At the end of follow up,
there was no more thrombosis or occluded anastomosis than the first cast.


## 3.2. Hemorrhage Complication

Four patients had hemorrhagic complications  requiring in all cases a surgical control. A portal vein
thrombosis was associated twice with a hemorrhagic complication. Three patients
received curative anticoagulant therapy. Surgical treatment of these hemorrhages needed
lavage, drainage, and thrombectomy in case of portal thrombosis.


## 3.3. Long-Term Outcome

Mean of follow-up was23±31 months. Once the
early postoperative course wasachieved,
no more cases of portal thrombosis occurred. There was no more thrombosis or
occluded anastomosis than the first cast. Median disease-free survival was 16
months.


## 4. Discussion

Although PD offers the only chance of cure for patients with
adenocarcinoma of the pancreas, questions have arisen regarding the indication,
safety, and outcomes of patients undergoing extended resections for locally
advanced disease [6]. While a previous study demonstrated an overall survival
benefit after pancreatic resection without an increase of morbidity and
mortality rates [7–9], high
mortality rate was
reported for patients with portal vein thrombosis [10–13]. Few studies  have focused on
different types of surgical venous resections and different modes of
reconstruction of the portal vein [6–14].Few
studies presented a radiological classification in order to predict the
involvement of PV or SMV. Moreover, Nakao’s report showed that macroscopic
findings (classified into types A, B, C, or D according to preoperative
findings on the portal phase of superior mesenteric angiography) were
correlated with the histological invasion grades [15–17]. However, this
classification was based on angiography or CT scan. In contrast, the necessity
of curative anticoagulant therapy was evaluated by this preoperative
classification. Moreover, our classification of resection and reconstruction
permitted us to define the impact of resection of confluent and the
modification of blood flow.In this series, PD with venous resection was most commonly performed for
pancreatic carcinoma. Most patients (89%) underwent a lateral venous resection
with reconstruction by lateral venorrhaphy. Venous thrombosis rate reached 0%,
38%, and 100% for type I, II, and IV resections, respectively. One lateral venorrhaphy
needed a patch of saphenous vein. Thrombosis occurred early after surgery, with
an acute setting; no case of thrombosis appeared secondarily, at distance from
the surgical removal of the tumor (after 6 months of follow-up). This result
was in agreement with Leach’s study which reported a thrombosis rate of 25%
[10].Moreover, in case of type II resection, patients with a portal resection
length over 2 cm, or with PTFE reconstruction, received anticoagulation with
intravenous heparin. In Leach's study, thrombosis rate raised to 25% despite
the onset of a lasting treatment by low dose of aspirin [10].This systematic onset of anticoagulation did not protect against venous thrombosis. These poor results were in accordance with
Smoot's study which showed no difference in the rate of portal thrombosis
between patients undergoing anticoagulant therapy and those without such
treatment (P=.65) [6]. These results were confirmed in Carrere's study
which demonstrated that only two cases of thrombosis occurred in patients under
curative heparinotherapy [14]. Hemorrhagic complication  increased
after PD and anticoagulation. In Carrere's study, hemorrhage complications
occurred after resection followed by postoperative curative anticoagulation. It
required the immediate interruption of the anticoagulant therapy [14]. In our
study, hemorrhage complications required 4 reinterventions. In fact, thrombosis
appeared to be more affected by the type of reconstruction rather than by the
anticoagulant treatment.Lateral resection with lateral venorrhaphy on the confluent (SMV) must
be avoided and replaced by a circumferential resection with end-to-end
anastomosis which appears to be the best technique. According to Nakao and
Fortner, the defect of the portal venous system is repaired by pushing the base
of the small bowel mesentery upwards and achieving an end-to-end anastomosis of
the superior mesenteric vein to the portal vein [18, 19].If the defect overreaches 7 cm or when mobilization of the base bowel is
insufficient or not achievable, Smoot's technique using left renal vein should
be preferred [20]. This technique allows staying in the same operative field;
moreover, caliber and thickness of the venous renal wall are similar to those
of the portal vein. According to Mitsuta’s study, reimplantation of the SV must
take into account the direction of its flow [21].In conclusion, after portal vein resection achieved in the course of a
PD, a lateral resection and reconstruction with venorrhaphy should be chosen
only when located 1 cm above the splenomesenteric confluent. When resection of
confluent is required, circumferential resection with end-to-end anastomosis
should be achieved. If this type of reconstruction appears to be impossible,
the use of a PTFE graft must be avoided and the left renal vein can be a
warranty used to carry out the venous reconstruction. Whatever might be the
technical choice of venous reconstruction, curative postoperative
anticoagulation does not prevent efficiently the onset of thrombosis.



---

*Source: 896320-2008-11-23.xml*