Efficacy of Long-acting Somatostatin Analogs in Recurrent Variceal Bleeding in a Patient with Pre-hepatic Portal Vein Thrombosis

Delotvornost leka dugotrajnog dejstva analognog somatostatina kod bolesnice sa ponovljenim varikoznim krvarenjem i trombozom prehepatične portne vene Abstract Introduction. Bleeding from esophageal varices is a serious medical problem because of the risk of recurrent bleeding and high mortality rate (17–54%). Gastroesophageal varices develop in 50% of cirrhotic patients with portal hypertension, but can also develop in other pre-or post-hepatic causes of portal hypertension. Case report. We reported a 48-year-old female patient with portal hy-pertension caused by mesenterial vein thrombosis due to congenital thrombophilia. The patient was hospitalized several times because of recurrent gastroesophageal bleeding. Thrombosis of portal , lienal and mesenteric veins was diagnosed using multislice computed tomography (MSCT) angiography. Sclerotherapy and/or variceal ligation could not be used due to variceal size and distribution. Beta blockers were ineffective. Balloon tamponade and octreotide were used in each massive bleeding episode. Carvedilol therapy was introduced but rebleeding occured. Surgical treatment was considered a high risk procedure due to massive thrombosis of mesenterial veins, patient`s general condition and high risk of postoperative thrombotic events. Thus, long-acting


Introduction
The most important cause of portal hypertension is liver cirrhosis, nevertheless portal vein thrombosis can also occur as a consequence of procoagulant mutations.Factor II G20210A is a mutation found in 4 out of 10 patients with idiopathic portal vein thrombosis (PVT) 1 .

Fig. 1 -Macroscopic appearance of gastric varices and hypertensive gastropathy>
Variceal hemorrhage is the most serious complication of portal hypertension and accounting for 17-57% of all deaths in cirrhotic patients 2,3 .The prognosis associated with variceal bleeding is overall much better in patients without significant liver impairment, ie those with non-cirrhotic portal vein thrombosis.The main therapeutic goals in patients with gastroesophageal varrices is prevention of initial bleeding episode, control of acute varriceal bleeding and prevention of recurrent variceal bleeding.Endoscopic sclerotherapy, endoscopic variceal ligation and pharmacological treatment today have the overall success rate of 90%.
We presented a patient with recurrent variceal bleeding due to mesenterial vein thrombosis caused by congenital thrombophilia in whom long-acting somatostatin analogue was successfully used in control of repeated variceal bleeding for 3 months allowing patient stabilization and careful elective surgery planning.

Case report
A 48-year-old female was admitted with massive hematemesis and melena to the Clinic.Emergency esophagogastroduodenoscopy (EGD) revealed bleeding and esophageal and gastric varices (Figure 1.).Bleeding was controlled using blood volume restitution, vasoactive drugs and balloon tamponade.The personal history of the patient revealed 8 spontaneous miscarriages, one complicated with ileus.At the age of 28 variceal bleeding occurred, was treated with beta blockers and for 20 years no rebleeding occured.At the age of 44, routine ultrasound examination revealed enlarged spleen and PVT and congenital thrombophilia (mutation of protrombin gene G20210A) was diagnosed.
Thrombosis of portal, lienal and mesenteric veins was diagnosed using MSCT angiography.After repeated EGD it was concluded that sclerotherapy and/or variceal ligation would not be adequate solution due to variceal size and distribution.Beta blockers were introduced, but recurrent variceal bleeding occurred leading to multiple hospital admissions and blood transfusions.Balloon tamponade was used in massive bleeding episodes as a temporary therapy until definitive treatment.Octreotid was used for five days, but every time the therapy was discontinued, rebleeding occurred.oral and parenteral treatment with beta blockers and the patient became dependent on continuous infusion of somatostatin analogs.At the same time acute deep venous thrombosis of the left leg developed and low-dose anticoagulant was introduced (nadroparin 2,500 ij sc/day).Carvedilol therapy was introduced according to Baveno V consensus but rebleeding occured.At that point surgical treatment was considered to be high risk procedure due to massive thrombosis of mesenterial veins, patient`s general condition and high risk of postoperative thrombotic events.Thus, long-acting somatostatin analogue -Sandostatin ® LAR was initiated at a dose of 30mg i.m./month.The patient responded to therapy well and variceal bleeding did not occur for the following 3 months.
After 3 months another episode of gastric variceal hemorrhage occurred and surgical treatment was reconsidered.Total gastrectomy was performed in order to prevent repeated bleeding from large gastric varices and the patient recovered successfully (Figures 2 and 3).

Discussion
In non-cirrhotic portal hypertension endoscopic therapy is effective for control of acute variceal bleeding, while for secondary prophylaxis preliminary evidence suggests beta blockers to be as effective as endoscopic ligation.Decompressive surgery or interventional radiological procedures are considered in patients with failure of endoscopic therapy 3 .
The Baveno V criteria do not provide consensus on the indications for anticoagulant treatment of extra hepatic portal vein thrombosis 3 , but in our patient it was initiated for acute deep venous thrombosis of the left leg.
Somatostatin analogue octreotide is used for decades in treatment of acute variceal haemorrhage, with the well-known mechanisms of lowering portal pressure.It increases efficacy of endoscopic therapy and decreases rebleeding risk [4][5][6][7] .
In the presented patient after all the other therapeutic options failed we introduced Sandostatin ® LAR as an attempt of rescue therapy.Namely, data published by Spahr et al. 8 suggested that prolonged administration of a long-acting formulation of octreotide improves significantly portal hypertension in carefully selected cirrhosis patients.Sustained decrease in splanchnic hyperemia was proposed as underlying pharmacological mechanism of octreotid 8 .

Conclusion
Long-lasting somatostatin analogue was used for the first time in treatment of gastroesophageal variceal hemorrhage in the patient with prehepatic portal hypertension.It was effective as temporary therapeutic option allowing the improvement of the patient's general condition and adequate planning of elective surgical procedure.Futher reports are needed in order to compare efficacy in treatment of patients with variceal bleeding, where poor outcome is expected.

Fig. 2 -Fig. 3 -
Fig. 2 -Perigastric devascularization -A) Surgical instrument inserted between greater curvature of the stomach, and the epiploic arcade along greater curvature; B) Great curvature of the stomach detached from the epiploic arcade.