MANAGEMENT CONFERENCE

1. MANAGEMENT CONFERENCE A middle age woman with abdominal pain and ascitis

2. CC: a 54 yr old woman presented with Abd.pain and ascitis from 2 m. ago Pain charactristics: Epigastric / RUQ Refer to back Continious / Dull / Moderately severe No correlation with eating or position With nausea / No vomitting Worsened pain from 2 w.ago with reduced appitide.

3. Moderate abdominal distention • Suspicious W.L • No fever & Icter • Constipation in the last week • No diarrhea • PMH: 2 ocassion of first trimester abortion Pulmonary TB in remote past Lower extrimities edema & varrices Suspicious DVT in 2ys ago • DH / Habits / FH: Unremarkable

4. Physical Examination • Vital signs: NL • Conj: Mildly pale / No icter & LAP • JVP: NL / Scorofula scar on neck • NL S1,2 / Fine EI crackles in RT lower lobe • Abd: tenderness in epigastic & RUQ No collatrals & Organomegaly No detectable acsites by PE. • No edema in lower EXT.

5. Lab data • CBC : WBC 6400 /HB 12.8 / PLT 119000 • PT 15.3 / INR 1.8 / PTT 44 • ESR 33 / CRP 1+ • RFT NL / LFT & ALP & BIL & Amylase NL • Viral markers : Neg / SAAG: 2 (S 3.5,A 1.5) • SPEF: Alb 3 g% -, Gama.glu 1.3 g% + • PPD : NEG • CEA & CA19-9 : NEG • ANA :13 / Anti ds-DNA 42 • APLA & ACLA : Not elevated

6. DDx • Portal vein thrombosis • Cirrhosis • Intraabdominal or pelvic malignancy • TB Peritonitis • CVD

7. Ultrasonography • Liver : 100mm / Heterogenic echo • GB : NL / Contain sludge • PV : 11mm • Spleen : 112x42mm / NL echo • No ascites & LAP • Pancreas : NL • Small RT ovarian cyct

8. EGD • Fundal varrices • Snake skin appearance of body & fundal mucosa.

9. CXR

10. Abdominal & Pelvic CT scan

17. Doppler ultrasonography

18. Endosonography report

19. Laparoscopic findings

20. Causes of portal vein thrombosis • Abdominal sepsis • Cirrhosis • Collagen vascular diseases (eg, lupus) • Compression or invasion of the portal vein by tumor (eg, pancreatic cancer) • Endoscopic sclerotherapy • Factor V Leiden • Hepatocellular carcinoma • Inflammatory bowel disease • Myeloproliferative syndromes • Omphalitis • Oral contraceptives • Pancreatitis • Paroxysmal nocturnal hemoglobinuria • Pregnancy • Protein C deficiency • Prothrombin gene mutation • Retroperitoneal fibrosis • Transjugular intrahepatic portosystemic shunt • Trauma

21. In adults, approximately 25% of patients with portal vein thrombosis have underlying cirrhosis. • The annual incidence of portal vein thrombosis among patients with cirrhosis is less than 1 percent. • No apparent cause for portal vein thrombosis is evident in more than one-third of patients.Many of these patients probably have an underlying hypercoagulable state.

22.   Acute portal vein thrombosis is usually clinically silent, and is often diagnosed during radiologic examination for other reasons (such as acute pancreatitis). the thrombosis often resolves spontaneously within days to weeks. • Chronic portal vein thrombosis may either produce a chronic noncavernous thrombosed portal vein or cavernous transformation of the portal vein. • Cavernous transformation refers to the development of collateral blood vessels that bring blood in a hepatopedal manner from the region of obstruction.

23. Clinical manifestations • The most common clinical manifestation of chronic portal vein thrombosis is variceal hemorrhage, which occurs at least once in 50 to 70 percent of patients and at least twice in 30 percent . • More than 85 to 90 percent of patients with chronic portal vein thrombosis have esophageal varices, while 30 to 40 percent have concomitant gastric varices. •  Approximately 50 percent of patients with chronic portal vein thrombosis have splenomegaly, which may be massive; 10 percent of these patients have anemia, thrombocytopenia, and leukopenia.

24.   A small amount of ascites is present in about 10 percent of patients. patients typically do not have significant ascites unless they develop acute dilutional hypoalbuminemia during fluid resuscitation for a variceal bleed or have associated cirrhosis. •  Jaundice, which is present in approximately 5 percent of patients, is usually related to concomitant hepatobiliary disease. •   Infection of the thrombosed portal vein (pylephlebitis) should be considered in patients with fever and bacteremia or sepsis in addition to the clinical manifestations described above.

25. MANAGEMENT • Patients in whom portal vein thrombosis is suspected should undergo radiologic testing to define the extent of the clot. Ultrasound with Doppler flow studies, CT scanning, and MRA are often helpful in this setting. Venous phase angiography remains the gold-standard in patients in whom the diagnosis is strongly suspected, but the above studies are unrevealing. • Most patients with portal vein thrombosis should undergo evaluation for a hypercoagulable state.

26.   Several anecdotal reports have documented successful lysis of acute portal vein thrombosis using SK or TPA administered locally by a catheter passed via a transjugular transhepatic or percutaneous transhepatic route. •   The treatment of chronic portal vein thrombosis depends upon the stage of the disease and the patient's comorbidities. Although there are no controlled data, it is reasonable to administer nonselective beta blockers to decrease the risk of variceal bleeding. • There is no role for anticoagulation in patients who have already developed cavernous transformation.

27. Chronic anticoagulation is a reasonable option in a very select subset of patients with recent onset of disease who: • Do not have underlying liver disease. • Have an acute or subacute symptomatic presentation. • Do not have evidence of a recanalization already underway. • Additional definitive salvage therapy should be considered for patients who experience repeated hemorrhage despite adequate endoscopic treatment, have isolated varices in the gastric fundus, or have ectopic varices. Surgery is the "gold-standard" for the treatment of such patients since it permanently corrects the varices and is usually well-tolerated because liver function typically remains well-preserved.

28. TIPS may be possible in patients without cavernous transformation. However, TIPS is not an attractive option because of the need to monitor for TIPS stenosis, the requirement for repeated angiography to maintain TIPS patency. • Anticoagulation in patients with chronic portal vein thrombosis should be decided upon on a case by case basis weighing the risk of bleeding versus thrombosis and the patient's ability to survive a bleed versus a thrombotic event. It may be desirable in those at high risk for recurrent thrombosis based upon clinical history of laboratory studies.

29. The etiologic distribution of thrombophilic factors in chronic PVTDepartment of Gastroenterology, Ankara, Turkey.J Clin Gastroenterol. 2007 May • GOALS: We aimed to prospectively investigate the full etiologic contributors to portal vein thrombosis. • STUDY: 59 patients were included in the study who had normal liver functions, normal liver histology and studied the thrombophilia factors of both acquired factors and congenital factors. • RESULTS: In all, 23.7% of the patients were found to have acquired thrombophilia factors like myeloproliferative disorders, whereas 22.1% of the patient population was found to harbor no identifiable cause of thrombophilia, which we termed as idiopathic. One or more causes of thrombophilia were identified in 46 patients. There were 27 patients with protein C deficiency, 18 patients with protein S deficiency. The antithrombin deficiency was found in 17 patients. The factor V Leiden mutation was found in 7 patients. There were 3 patients with prothrombin mutation.

30. Portal vein thrombosis; risk factors, clinical presentation and treatment.Department of Hepatology and Gastroenterology.Denmark.BMC Gastroenterol. 2007 Aug • METHODS: 67 patients were identified in the electronic records from 1992 to 2005. • RESULTS: One or more risk factors were present in 87%. Symptoms were abd.pain, splenomegaly, fever, ascites, haematemesis, and weight loss. Abd.pain and fever occurred more frequently in patients with acute PVT. Frequent complications were splenomegaly, oesophageal- and gastric varices with or without bleeding, portal hypertensive gastropathy and ascites. Varices and bleeding were more frequent in patients with chronic PVT. Patients who received anticoagulant therapy more frequently achieved partial/complete recanalization. Patients with varices who were treated endoscopically in combination with beta-blockade had regression of the varices. The overall mortality was 13% in one year, and was dependent on underlying causes. • CONCLUSION: We observed that partial/complete recanalization was more frequent in patients treated with anticoagulation therapy, and that regression of varices was more pronounced in patients who where treated with active endoscopy combined with pharmacological treatment.

31. PVT: etiology, diagnostic strategy, therapy and management.Klinik für Strahlenheilkunde, Berlin, Germany.Vasa. 2005 May • Myeloproliferative disorder, liver cirrhosis with portal hypertension, deficiency of anticoagulant proteins, gene mutation and hepatocellular carcinoma are the most frequent causes of portal vein thrombosis (PVT). • Fresh thrombus can be undetected in sonography due to the low echogenity but can be recognized in color Doppler sonography.Contrast-enhanced 3D MRA allows a comparable accuracy in the detection of PVT as digital subtraction angiography. • Therapeutical options of PVT consist of mechanical recanalization of the portal vein, local fibrinolysis with or without placement of TIPS, combination of mechanical recanalization and local fibrinolysis, systemic thrombolytic therapy, anticoagulation alone and surgical thrombectomy. • Once PVT is found in sonography, Doppler sonography may be performed in order to distinguish benign from malignant thrombus. If further information is needed, MR angiography or contrast enhanced CT is the next step. If these tests are unsatisfactory, digital subtraction angiography should be performed. • Today, in symptomatic noncavernomatous PVT, recanalization with local methods is recommended. Additional implantation of TIPS should be performed when the patient is cirrhotic. In recent PVT in non-cirrhotic patients anticoagulation alone is recommended. It is expected that in old PVT anticoagulation can prevent further extension of the thrombus.

32. PVT: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies.Department of Vascular Surgery, Uppsala University Hospital, Sweden. World J Gastroenterol. 2006 Apr • METHODS: Between 1970 and 1982, 23,796 autopsies, representing 84% of all in-hospital deaths in the Malmö city population, were performed, using a standardised protocol including examination of the portal vein. • RESULTS: The population prevalence of PVT was 1.0%. Of the 254 patients with PVT 28% had cirrhosis, 23% primary and 44% secondary hepatobiliary malignancy, 10% major abdominal infectious or inflammatory disease and 3% had a myeloproliferative disorder. Patients with both cirrhosis and hepatic carcinoma had the highest PVT risk, OR 17.1 (95% CI 11.1-26.4). In 14% no cause was found; only a minority of them had developed portal-hypertension-related complications. • CONCLUSION: The markedly excess risk in cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients for whom prospective studies of directed intervention might be considered.

33. Acute portal vein thrombosis and massive necrosis of the liver. An unusual complication after stenting for chronic pancreatitis.Department of Surgical, Gastroenterology .Medical College Hospital, India.JOP. 2006 Nov • A 32-year-old man presented with severe upper abdominal pain radiating to the back, associated with vomiting and abdominal distension. The patient was diagnosed as having had chronic calcific pancreatitis recently and had undergone ERCP with pancreatic duct stenting. Two days after the procedure, the patient developed severe abdominal pain, vomiting and abdominal distention. Investigation revealed massive liver necrosis and portal vein thrombosis. This patient had a life-threatening complication following pancreatic duct stenting for chronic pancreatitis and was managed medically. • CONCLUSION: Therapeutic pancreatic endoscopy procedures should be restricted to high volume centers. In a good surgical candidate, it is better to avoid stenting.

34. Laparoscopy-associated portal vein thrombosis: description of an evolving clinical syndrome.Department of Surgery, Augusta Victoria Hospital, UK.J Laparoendosc Adv Surg Tech A. 2006 Feb • Several cases of portal vein thrombosis following laparoscopic procedures have been reported over the past few years. we summarize and analyze the features of the 4 reported cases to date as well as a fifth case encountered at our institution. The probable causes of this complication include changes in coagulation status, splanchnic hemodynamics, and portal venous blood flow, all of which may be related to carbon dioxide absorption and increased intra-abdominal pressure.

35. Superior mesenteric and portal vein thrombosis caused by congenital antithrombin III deficiency: report of a case.Department of Surgery, Oita Prefectural Hospital, Oita, Japan.Surg Today. 2007 • A 50-year-old man presented with a 24-h history of gradually worsening abdominal pain. Enhanced CT showed segmental dilation of the small intestine, wall thickening, and ascites, as well as thrombosis of the superior mesenteric vein (SMV) and portal vein. Thus, an emergency laparotomy was performed, which revealed segmental intestinal infarction caused by the thrombosis in the SMV and portal vein. We resected the necrosed intestine and performed anastomosis. The patient was given intravenous heparin and nafamostat mesilate as anticoagulation therapy. The abdominal pain again recurred 4 days after this operation, necessitating a second laparotomy. Segmental congestion of the intestine was found and another resection was done, after which he recovered rapidly. Blood chemistry subsequently revealed an antithrombin III deficiency, which was confirmed to be inherent, after screening his family. Thus, laboratory testing for these proteins may help define the cause of mesenteric venous thrombosis.

36. Nonmalignant portal vein thrombosis in adults.Service d'Hépatologie, Hôpital Beaujon, France.Nat Clin Pract Gastroenterol Hepatol. 2006 Sep • Local risk factors for PVT, such as an abdominal inflammatory focus, can be identified in 30% of patients with acute PVT; 70% of patients with acute and chronic PVT have a general risk factor for PVT, most commonly myeloproliferative disease. Early initiation of anticoagulation therapy for acute PVT is associated with complete and partial success in 50% and 40% of patients, respectively. A minimum of 6 months' anticoagulation therapy is recommended for the treatment of acute PVT. For patients with either form of PVT, permanent anticoagulation therapy should be considered if they have a permanent risk factor. In patients with large varices, beta-adrenergic blockade or endoscopic therapy seems to prevent bleeding as a result of portal hypertension, even in patients on anticoagulation therapy. Overall, the long-term outcome for patients with PVT is good.

37. Thrombolytic treatment of portal thrombosis.Department of General & Liver Surgery .Warsaw, Poland.Hepatogastroenterology. 2003 Nov • METHODS: the authors present a retrospective review of 33 cases of rapidly developing portal thrombosis. 16 female patients were regularly using oral contraceptives, in 8--portal thrombosis coexisted with the Budd-Chiari syndrome, in another 8--with polycythemia or myeloproliferative disorders and in 1 was observed during acute liver failure following paracetamol ingestion. • RESULTS: Conservative treatment was unsuccessful in the first 5 cases: all of them died from esophageal variceal bleeding and liver failure. The next 28 patients received fibrinolytic treatment with streptokinase (3 cases) or rTPA. Rapid improvement of general condition, with Doppler sonography signs of the portal vein recanalization was noted in 10 patients, in all of whom the history of the disease did not exceed 14 days. In 13 patients with the longer history, partial portal vein occlusion persisted, but restored hepatopetal flow was sufficient to assure normal liver function. In the remaining 5 patients, with the history of the disease lasting longer than 30-40 days, the treatment failed and no clinical or Doppler sonography evidence of restoring of the portal flow were demonstrated. 4 patients died: 2 from portal rethrombosis, 1 from liver failure and 1 from cerebral stroke. • CONCLUSIONS: Thrombolytic treatment of acute portal thrombosis, if administered promptly, appears to be the only way to improve, or even restore, the portal system patency.

38. Current outcome of PVT in adults: risk and benefit of anticoagulant therapy.Service d'hépatologie et INSERM.Paris, France.Gastroenterology. 2002 Jun • BACKGROUND & AIMS: We assessed current outcome and predictors of bleeding and thrombotic events in a cohort of 136 adults with nonmalignant, noncirrhotic portal vein thrombosis, of whom 84 received anticoagulant therapy. • RESULTS: Median follow-up was 46 months. The incidence rate of gastrointestinal bleeding was 12.5 (95% confidence interval [CI], 10-15) per 100 patient-years. Large varices were an independent predictor for bleeding. Anticoagulant therapy did not increase the risk or the severity of bleeding. The incidence rate of thrombotic events was 5.5 (95% CI, 3.8-7.2) per 100 patient-years. Underlying prothrombotic state and absence of anticoagulant therapy were independent predictors for thrombosis. In patients with underlying prothrombotic state, the incidence rates of splanchnic venous infarction were 0.82 and 5.2 per 100 patient-years in periods with and without anticoagulant therapy, respectively (P = 0.01). Two nonanticoagulated patients died of bleeding and thrombosis, respectively. CONCLUSIONS: In patients with portal vein thrombosis, the risk of thrombosis is currently as clinically significant as the risk of bleeding. The benefit-risk ratio favors anticoagulant therapy.

39. TIPS placement in patients with cirrhosis and concomitant PVT Department of Radiology, The University of Chicago, USA.Cardiovasc Intervent Radiol. 2006 Sep • METHODS: This study reviewed 15 cases of TIPS creation in 15 cirrhotic patients with portal vein thrombosis at our institution over an 8-year period. There were 2 women and 13 men with a mean age of 53 years. Indications were refractory ascites, variceal hemorrhage, and refractory pleural effusion. • RESULTS: The technical success rate was 75% (3/4) in patients with chronic portal vein thrombosis associated with cavernomatous transformation and 91% (10/11) in patients with acute thrombosis or partial thrombosis, giving an overall success rate of 87%. Complications included postprocedural encephalopathy and localized hematoma at the access site. In patients with successful shunt placement, the total follow-up time was 223 months. The 30-day mortality rate was 13%. Two patients underwent liver transplantation at 35 days and 7 months, respectively, after TIPS insertion. One patient had an occluded shunt at 4 months with an unsuccessful revision. The remaining patients had functioning shunts at follow-up. • CONCLUSION: TIPS creation in thrombosed portal vein is possible and might be a treatment option in certain patients.