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DISEASES DISORDERS OF THE LIVER

Primary Liver Cancer . Liver malignancy may arise from hepatocytesBiliary epithelial cells. Primary Liver Cancer. uncommon in the USA, but its incidence is increasing.In Asia and Africa > primary liver cancer is extremely commonover age 50, but a few are found in children, mainly under 2 yea

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DISEASES DISORDERS OF THE LIVER

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    1. DISEASES & DISORDERS OF THE LIVER Angel M. Rodriguez PGY-2 Mercy Catholic Medical Center

    2. Primary Liver Cancer Liver malignancy may arise from hepatocytes Biliary epithelial cells

    3. Primary Liver Cancer uncommon in the USA, but its incidence is increasing. In Asia and Africa > primary liver cancer is extremely common over age 50, but a few are found in children, mainly under 2 years of age.

    4. Risk Factors - HCC Chronic HBV and HCV Cirrhosis chronic underlying liver disease.

    5. Risk Factors - cholangioCA infrequently associated with cirrhosis. Primary sclerosing cholangitis Widespread infection with liver flukes (Clonorchis sinensis

    6. Primary Liver Cancer A large proportion of patients will have intra- or extra-hepatic metastases at presentation. infiltration of the portal venous system with subsequent dissemination of tumor cells. Vascular invasion is more common with larger tumors (> 5 cm). Most common mets include the hilar and celiac lymph nodes and the lungs; metastases to bone and brain are less common and peritoneal disease (ie, carcinomatosis)

    7. Primary Liver Cancer Cholangiocarcinoma ~ 15% Well-differentiated adenocarcinomas that spread invasively in the liver substance. Often grow to a large size Angiosarcoma, a rare fatal tumor, has been seen in workers exposed to vinyl chloride.

    8. DX percutaneous core biopsy or aspiration biopsy. Fine-needle aspiration A negative result therefore does not rule out malignant disease In patients with cirrhosis, the presence of a hypervascular mass > 2 cm on two different imaging studies or a hypervascular mass > 2 cm on one imaging study combined with a serum alpha-fetoprotein level > 400 ng/mL is dx of HCC

    9. Tumor Marker - AFP hepatomas and testicular tumors. upper limit of normal is 20 ng/mL; values above 200 ng/mL are suggestive of hepatoma >400 ng/mL in a cirrhotic patients with a hypervascular liver mass > 2 cm in diameter are dx.

    10. TX-Partial Hepatectomy most effective therapy minimal criteria o disease confined to the liver disease amenable to a complete resection. For small and peripherally placed lesions, sublobar, segmental resections are preferred Anatomical segmentectomies are preferred to non-anatomical resections.

    11. TX-Partial Hepatectomy cirrhosis constitutes the major obstacle to resection in patients with HCC. Careful patient selection cirrhotic patients have a late risk of death highly selected patients may be better treated with liver transplantation rather than resection.

    12. Child-Pugh Classification of Severity of Liver Disease

    13. Partial Hepatectomy recurrence is 70% at 5 years. 5-year survival rate is 40%

    14. Liver Transplantation HCC treating not only the malignant disease but also the underlying cirrhosis. most likely to benefit > single tumor = 5 cm in diameter or up to three tumors with none exceeding 3 cm in diameter. Using these criteria, 5-year survival is 70% benefit of transplantation only when the waiting time for a new graft is < 6 months.

    15. Liver Transplantation At present, transplantation has no role in patients with cholangiocarcinoma outside of controlled clinical trials, since the results to date have been poor.

    16. ETHANOL INJECTION small unresectable HCC 95% ethanol is injected t directly into the tumor. achieve complete necrosis in 90–100% of tumors < 2 cm, but its efficacy declines rapidly as the tumor size increases. In one multi-institutional series from Italy, survival 1, 2, and 3 years after treatment for patients with solitary, small tumors was 90%, 80%, and 63%, respectively.

    17. Radiofrequency Ablation Percutaneous approach unresectable, small tumors needle is attached to a radiofrequency generator that generates thermal energy limited by tumor size A randomized study comparing the two techniques found no differences in survival, although RFA may offer better local tumor control rates.

    18. Arterial Embolization fact that primary liver cancers derive disproportionately greater blood supply from the hepatic arterial circulation compared to the surrounding liver. The strategy is to combine selective hepatic arterial injection of cancer chemotherapeutic agents with arterial embolization, the latter to produce tumor necrosis and slow the washout of the drugs. Embolization can be used in patients with much larger tumors than can be effectively treated with percutaneous procedures, and the procedure can be staged to treat bilobar disease. Patients must have adequate liver function; those with Child class C cirrhosis or thrombosis of the portal vein are not suitable candidates.

    19. METASTATIC NEOPLASMS 20 times more common than primary tumors in the liver via the systemic or portal venous circulation colon, pancreas, esophagus, stomach, neuroendocrine, breast, lung, kidney, adrenal, ovary and uterus, melanoma, and sarcomas

    20. TX most > chemotherapy is the only treatment option

    21. HEPATIC RESECTION most commonly indicated in patients with metastatic colorectal cancer If a complete resection is done, the 5-year survival rate is 25–40%. The presence of extrahepatic metastases and inability to achieve a complete resection are contraindications The mortality rate is 1–2% in hospitals where this operation is performed frequently.

    22. HEPATIC RESECTION The liver is the most common site of cancer recurrence after a complete resection. may be amenable to a second resection. patients with metastases from renal cell carcinoma, ovarian cancer, adrenocortical carcinoma, or sarcomas appear to derive the most benefit.

    23. Radiofrequency Ablation The indications for this procedure remain ill-defined. The best candidates are > limited number of small liver lesions with no evidence of extrahepatic cancer.

    24. CHEMOTHERAPY In a large proportion of patients with metastatic colorectal cancer, the liver is the only evident site of disease. If the lesions cannot be resected regional intrahepatic chemotherapy is an option Systemic chemotherapy is usually given concomitantly. The discovery of extrahepatic lesions at laparotomy for pump placement is a relative contraindication to proceeding with this approach.

    25. Hemangiomas most common benign hepatic tumor up to 75% of patients are female The only reasons to resect hemangiomata are for symptoms, most commonly pain, or diagnostic uncertainty.

    26. Cysts Simple hepatic cysts, the most common, are unilocular fluid-filled lesions that generally produce no symptoms. The possibility of echinococcosis should be considered. Solitary cysts lined with cuboidal epithelium are classified as cystadenomas and should be resected, since they are premalignant. There are few indications for aspirating hepatic cysts.

    27. Cysts Large symptomatic cysts are difficult to eradicate with alcohol injections, and serious superinfection of the cyst cavity may occur. The simplest method consists of laparoscopic cyst fenestration (wide excision of the cyst wall). A tongue of omentum is fixed so it lies in the residual cyst cavity as an ancillary measure to prevent the edges from coapting.

    28. Hepatic Adenoma oral contraceptives - Small adenomas may regress when agents are discontinued Two-thirds are solitary Transition from benign to HCC may occur association of acute bleeding episodes with pregnancy. The general consensus is that adenomas should be resected because of the risks of malignant change and spontaneous hemorrhage. Symptomatic and large asymptomatic should be resected. Emergent resection or hepatic artery embolization for hemorrhage.

    29. Focal Nodular Hyperplasia young women oral contraceptive agents does not appear to predispose to the development of FNH Symptomatic lesions should be removed, while asymptomatic tumors (the majority) should be left undisturbed Inability to distinguish FNH from adenoma or malignant disease is an indication for resection in some patients. Discontinuation of oral contraceptives probably has no impact.

    30. CIRRHOSIS Mortality 23,000 per year in the USA alone. The incidence of the cirrhosis is increasing, due in large measure to hepatitis C, and at present is the third most common cause of death in men in the fifth decade of life. Alcohol abuse remains the leading cause of cirrhosis in most Western countries. up to 30% of patients die within a year from hepatic failure or complications of portal hypertension A group of cirrhotics with varices followed by the Boston Interhospital Liver Group experienced a 1-year death rate of 66%. Bleeding episodes occur in up to 40% of all patients with cirrhosis, and the initial episode of variceal hemorrhage is fatal in 50% or more. At least two-thirds of those who survive their initial hemorrhage will bleed again

    31. Portal Hypertension Normal pressure ranges from 7 to 10 mm Hg. In portal hypertension, pressure exceeds 10 mm Hg, averaging around 20 mm Hg and occasionally rising as high as 50–60 mm Hg. In extrahepatic portal vein thrombosis (without liver disease), collaterals in the diaphragm and in the hepatocolic, hepatoduodenal, and gastrohepatic ligaments transport blood into the liver around the occluded vein (hepatopetal). In cirrhosis, collateral vessels circumvent the liver and deliver portal blood directly into the systemic circulation (hepatofugal); these collaterals give rise to esophageal and gastric varices.

    32. Portal Hypertension Isolated thrombosis of the splenic vein causes localized splenic venous hypertension and gives rise to large collaterals from spleen to gastric fundus. From there, the blood returns to the main portal system through the coronary vein. In this condition, gastric varices are often present without esophageal varices. spontaneous bleeding is relatively uncommon except from those at the gastroesophageal junction; spontaneous bleeding from gastric varices can sometimes occur. Compared with adjacent areas of the esophagus and stomach, the gastroesophageal junction is especially rich in submucosal veins, which expand disproportionately in patients with portal hypertension. The cause of variceal bleeding is most probably rupture due to sudden increases in hydrostatic pressure.

    34. Acutely Bleeding Varices half of patients with massive bleeding from varices die as a result of the acute event. Balloon tamponade is no longer used routinely Endoscopic sclerotherapy or banding is the initial therapy of choice. successful in approximately 90% of cases, but the early rebleeding rate is about 30%. When bleeding continues after initial treatment, an emergency shunt procedure should be considered. general, patients still bleeding after six units—>portal decompression procedures. Even when the bleeding is brought under control by the initial intervention, the mortality rate remains high (about 35%)

    35. Acute Endoscopic Sclerotherapy or Ligation controls acute bleeding in 80–95% of patients, and rebleeding during the same hospitalization is about half (25% versus 50%) the rebleeding rate of patients treated with a combination of vasopressin and balloon tamponade.

    36. Vasopressin and Terlipressin (Triglycyl Lysine Vasopressin) lowers portal pressure by constricting splanchnic arterioles Vasopressin alone controls acute bleeding in 80% of patients, and this increases to 95% when used in conjunction with balloon tamponade. Complications > MI, cardiac arrhythmias, and intestinal necrosis. side effects prevented with nitroglycerin or isoproterenol. controlled trials generally indicate that vasopressin plus nitroglycerin is superior to vasopressin alone. Vasopressin is given as a peripheral intravenous infusion (0.4 units/min). Nitroglycerin can be given intravenously or sublingually.

    37. Octreotide Acetate Somatostatin and the synthetic longer-lasting analogue octreotide have the same effect on the splanchnic circulation as vasopressin but without significant side effects. as effective as vasopressin in controlling acute variceal bleeding and are now the first choice for pharmacologic control.

    38. Balloon Tamponade The main effect results from traction applied to the tube, which forces the gastric balloon to compress the collateral veins at the cardia of the stomach. Inflating the esophageal balloon probably contributes little, since barium x-rays suggest that it does not actually compress the varices.

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