Bleeding Esophageal Varices in Patient With Liver Cirrhosis - Research Proposal Example

Can ultrasonic measurement of portal vein diameter and hemodynamics be used as predictive tool for bleeding esophageal varices in patient with liver cirrhosis? Author: Introduction In cirrhosis of liver, the main pathologic event is chronic and irreversible injury of the hepatic cellular architecture. This leads to process of ongoing degeneration and regeneration resulting in extensive fibrosis within the hepatic parenchyma as a result of necrosis of the hepatocytes. In response to that, the supporting framework of reticulin fibers collapse (Tublin et al., 2008). A simultaneous process of connective tissue regeneration leads to distortion of the vascular architecture within and across the hepatic lobules. This process is recognized to be the final common pathway for many forms of chronic liver injury (Maruyama et al., 2009). At one point in time, this fibrotic process becomes irreversible, and most clinical features or complications of cirrhosis of liver can be correlated to the extent of the injury and subsequent histological changes, rather than to the causes of these changes per se. There are effects of loss of functional hepatocytes, but which is relevant to this proposal is fibrosis and distortion of intrahepatic micro and macrovascular architectures leading to portal hypertension and its effects, which include dilatation of veins at the gastroesophageal junction, termed as gastroesophageal varices and splenomegaly (Merkel et al., 2003). The portal venous system anatomically is designed to carry 60 to 80% of the afferent blood to the liver. Unlike other venous systems in the body, there are no valves in the portal venous system. It is connected to the spleen, and at least one-fifth of the portal venous blood is contributed to by the spleen. The compression on the tiny portal venous radicles due to widespread parenchymal distortion and fibrous tissue overgrowth, the portal venous pressure increases. Hindrance of flow through the portal vein leads to extensive intrahepatic and selective extrahepatic communication between the systemic and portal venous systems (Choi et al., 2003). Out of these hepatofugal collateral pathways to channel blood from the obstructed portal systems into systemic circulation, the connection between portal and short gastric veins in the esophagus appears to be the most significant since they can lead to life-threatening bleeding, which is difficult to control (Merkel et al., 1985). Preintervention investigations designed to gain information about these collateral and abnormal communications are important, not only to assess the extent of the disease (Poynard et al., 1987), but also to predict inadvertent injuries during intervention leading to significant and critical bleeding. Classically endoscopy followed by angiography remained the gold standard investigative procedure for this purpose, but with the advent of other modalities of imaging, the cumbersome nature of the older investigative protocols appears to be possibly averted (Brandenburger and Regenstein, 2002). Given the high morbidity and mortality of variceal bleeding and practical experience of encountering patients late in the course, as an imaging technologist in the work area and organization, it was a vexing problem to find out or suggest a rapid and noninvasive method of predictive investigation to the clinicians with which they can institute the treatment as early as possible which can change the outcomes of these patients (Tsokos and Turk, 2002). Moreover, an easy and noninvasive modality for investigation can have financial benefits at the same time reducing invasive procedures such as an endoscopy and time required involving skilled personnel at the cost of less predictive value (Piscaglia et al., 2001). Review of Literature The portal venous pressure is normally low, in the range of 5 to 10 mmHg. A greater than 10 mmHg portal venous pressure justifies portal hypertension, which would arise from resistance to portal blood flow. All major clinical manifestations of portal hypertension can be correlated to portal-systemic collaterals, and these include bleeding from gastroesophageal varices, hypersplenism and splenomegaly, ascites, and chronic hepatic encephalopathy. Since the collateral hepatofugal flow is the major hemodynamic event, these can be correlated to retrograde blood flow to the low-pressure systemic venous circulation from the high-pressure portal circulation with the most prominent site being cardioesophageal junction leading to esophageal varices (Merkel et al., 2000). The left gastric vein has been recognized to be the most commonly visible variceal vein in a patient with portal hypertension. This appears to be dilated. When these are visible, they indicate presence of esophageal varices. A left gastric vein can be detected by Doppler ultrasonography. A diameter of 5-6 mm indicates portal hypertension (Kang et al., 2002). Thus far Endoscopy has been established to be the most reliable diagnostic procedure. The extent of esophageal varices may also be visualized by Doppler ultrasonography. It has been demonstrated that the risk of variceal bleeding from the esophagus can be correlated to its size (Tarzamni et al., 2008). High portal venous pressure is a determinant of this since larger varices have higher wall tension and have been noted to have higher risks of bleeding (Zhang et al., 2007). Doppler sonography can accurately measure flow volumes and other hemodynamic parameters through noninvasive means. Many studies have used this modality to establish a diagnosis through examination of relationship between hepatic cirrhosis, portal hypertension, and esophageal varix hemodynamics (Vyas et al., 2002). The Doppler can effectively quantify an increase in portal venous diameter or a decrease in flow velocity through portal vein as measures of portal hypertension. Previous studies have indicated correlation between portal hypertension and esophageal varices (Icer and Kara, 2007). Barakat had indicated Doppler flow waveform pattern to be a reliable indicator of existence of flow changes within the portal vein in cirrhotic patients (Barakat, 2004). Fernandez et al. had indicated successful use of Doppler ultrasound for quantification of portal blood flow; however, vessel cross sectional measurements were difficult to achieve (Fernandez et al., 1991). Bolognesi et al. (2000) indicated the usefulness of Doppler mediated evaluation of intrahepatic portal venous resistive and pulsatility indices as a reliable measure of portal hypertension (Bolognesi et al., 2000). Although some studies, such as Li et al. (2005) have indicated hemodynamics alone may not be suitable to predict the risk of variceal bleeding in patients with cirrhosis and have suggested left gastric vein hemodynamics to be a better parameter (Li et al., 2005), many other studies indicate, both waveform studies and portal Doppler flowmetry can reliably indicate and predict the size of the esophageal varices. Liu et al. (2008) indicated spleen-portal index to be a reliable and valid noninvasive index of esophageal varices in patients with established cirrhosis (Liu et al., 2008). Hypothesis Thus an imaging modality that can accomplish the documentation of portal venous pressure, extent of compression and its effects, and the alterations in the hemodynamic parameters may be able to quantify the extent of the portasystemic anastomosis and flow changes in the cardioesophageal junction since this system operates on the principle of total transmission of pressure due to lack of veins in the portal venous system (Nevens et al., 1998). Although clinically the varices can be documented reliably by endoscopy, this modality does not allow a prompt evaluation. Moreover, it fails to assess the portal system, and thus, this becomes an indirect support for the presence of portal hypertension (de Franchis et al., 2004). To complement this study, therefore, it needs measurement of portal venous pressure, which is difficult, costly, invasive, and associated with life-threatening complications even in the skilled hands due to associated thrombocytopenia. Moreover, performance of these procedures would need image guidance, making this procedure a multidisciplinary activity, involving time, money, people, and facilities, leaving the only alternative to have hepatic and mesenteric angiography. On the other hand, variceal bleeding is most common from the gastroesophageal varices. Although there are many hitherto unknown factors involved in variceal bleeding, the degree of portal hypertension in the range of greater than 12 mmHg and the size of the varices appear to be predictive of imminent variceal bleeding from this area (Jensen, 2002). Since variceal bleeding is life-threatening, can occur without any evident precipitating factors and a delayed treatment is often unsuccessful, a noninvasive modality of investigation that can predict the variceal bleeding in cases of portal hypertension in patients with cirrhosis may be of use to the clinicians in order to offer better results in such cases (de Franchis, 2005). This researcher hypothesizes that measurement of portal vein diameter and hemodynamics through ultrasonic Doppler method can be used as a predictive investigative tool to predict esophageal variceal bleeding in patients with hepatic cirrhosis. Research Question Can ultrasonic measurement of portal vein diameter and hemodynamics be used as predictive tool for bleeding esophageal varices in patient with liver cirrhosis? Aims and Objectives The aims and objectives of this study is to establish and develop a Doppler ultrasound based investigative modality with defined parameters to quantitate the extent of portal hypertension, hence severity of the disease in patients with cirrhosis of liver, where associated measurements of flow dynamics through portal vein and esophageal varices may provide predictive assessment of changes of variceal bleeding. This may provide an easy pathway to estimate the portal hypertension in such patients as opposed to the current endoscopic measures leading to the benefits of a cheaper, easier, and quicker clinically useful diagnostic modality, less need for invasive procedure, and less need of skilled professionals, ultimately helping speedy and appropriate interventions and fostering less morbidity and mortality as clinical outcomes in such cases. Ethical Considerations Due to this researcher’s work role as an imaging technologist in the little island nation of Grenada, an affiliation from the institution and hospital will be necessary. This study will be done under the supervision of my supervisor in the Department of Medical Imaging, and therefore, there would be need of clearance from the head of Medical Imaging. Since patients will be mainly referred from the Department of Medicine, an ethical clearance from the Head of the Medical Department will also be necessary. The hospital ethics committee will be approached for ethical clearance and a copy of this proposal will demonstrate that this study abides by all the ethical criteria for research in the hospital. Given the noninvasive nature of this study and given the possibility of better and clinically more useful outcomes from this study, there is an expectation that there is no reason for this study to be not cleared by the ethical committee. There is a necessity of QMU ethical approval. A consent form will be designed which would explain the nature of this study, and all recruits will be approached verbally, explaining the main themes of the study and the nature of the intervention in layman’s terms. Where possible, local language will be used for such verbal exchanges. There will be no coercion on the part of the researcher to motivate the patients to participate, and all identity details will be strictly confidential. A written consent form will be signed by and filed for each of the participants. For a peer review, the written consent form before use will be reviewed by the members of this researcher’s study group. Methodology Following ethical clearance, 100 consecutive patients who have been diagnosed to be having cirrhosis of liver will be recruited for this study. These patients will be recruited from the Medical Department who had been referred to the Medical Imaging Department in the St. Georges Hospital. The inclusion criteria will be a diagnosis of cirrhosis confirmed previously by liver biopsy in patients of any age and sex. Since a complication of cirrhosis of liver will change the scenario significantly, presence of any or more complications such as prior gastroesophageal bleeding, hepatorenal syndrome, portal vein thrombosis, on diuretic or vasopressin treatment, or with established signs of portal hypertension such as ascites, hepatic encephalopathy, or porta-systemic shunts will be excluded (Zironi et al., 1992). To establish esophageal varix before the study, the same gastroenterologist will perform upper gastrointestinal endoscopy following a color Doppler examination by a radiologist. To avoid observer bias, the radiologist and the gastroenterologist will be blinded to the respective results. The parameters that will be studied will be derived from literature, and they will be listed and systemically examined (Tarzamni et al., 2008). The endoscopy parameters will be presence and grade of esophageal varices and presence of varices in the stomach. If an esophageal varix is detected, the size of these varices will be graded according to Paquet grading. The research procedure and analysis of data collected will be done at the Department of Medical Imaging St Georges General Hospital in Grenada, equipments to be use will be the GE Logic 5 Pro Ultrasound Equipment in conjunction with the Olympus BFP200 endoscopic machine, and these are robust and reliable diagnostic equipments used by the same radiologist in every occasion. The parameters will be portal vein diameter, portal venous flow velocity, portal hypertensive index, congestion index, liver vascular index, and hepatic and splenic artery resistive indices, as indicated in other studies. Other studies have indicated the best technical details to get the relevant Doppler ultrasound images. The portal vein will be scanned longitudinally. The mean portal venous velocity in cm/s will be automatically measured with time average velocity across three cardiac cycles. An angle correction of less than 60 degrees will be done. This will be calculated by time average maximal velocity in cm/s and portal vein diameter (Liu et al., 2008). The hepatic artery resistive index and the hepatic artery pulsatility index will also be automatically calculated by the machine where resistive index will be given by the formula systolic velocity-end-diastolic velocity/systolic velocity when the cursor will be placed on the respective hepatic artery. Splenic artery resistive index will be measured at the hilum of the spleen through the parenchyma. Portal systemic collaterals and spleen size will be measured. The portal venous velocity/hepatic artery pulsatility index will give liver vascularity index. Portal venous cross sectional area/portal venous flow velocity will give portal venous congestion index. Portal hypertensive index will be given by the formula (Hepatic artery resistive index x 0.69) x (splenic artery resistive index x 0.87)/portal vein mean velocity (Tarzamni et al., 2008). Data Collection and Data Analysis All the data collected will be recorded along with the demographic data for each patient, and the data will be analyzed using SPSS Windows version 13. The patient characteristics will be expressed as mean values ± standard deviation and as percentage as the case may be. The interobserver agreement of ultrasonographic Doppler indices and the splenic index will be evaluated as coefficient of variation (Tarzamni et al., 2008). The issue of agreement between observers about endoscopic findings regarding esophageal varices will be evaluated with κ index. Univariate and multivariate logistic regression analysis with Wald test on all measured parameters will be done in order to identify independent factors indicating predictive indices for esophageal varices (Liu et al., 2008). Timeline This study will be done over a period of 1 year, out of which two months will be for preparation, six for experiment, two for data analysis and interpretation of the collected data, and the rest of 2 months for writing the thesis. The goal is to publish the literature in a reputed journal on radiology or gastroenterology in order to disseminate the information. Conclusion If the hypothesis proves to be correct, given the rigor of the research design, it is expected that the results of this study can be used in radiology imaging practice to offer a more suitable investigative modality for cirrhosis of liver in order to be able to predict variceal bleeding in a noninvasive, cost-effective, and rapid manner. 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