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研究生:張維洲
研究生(外文):Wei-Chou Chang
論文名稱:應用醫學影像參數評估肝臟及腸胃道疾病
論文名稱(外文):Imaging Assessment in Patients with Liver and Gastrointestinal Diseases
指導教授:陳潤秋陳潤秋引用關係林慶波林慶波引用關係
指導教授(外文):Ran-Chou ChenChing-Po Lin
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生物醫學影像暨放射科學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:119
中文關鍵詞:肝癌組織學分級肝移植卜邁維斯動態顯影的肝細胞相磁共振成像彌散加權成像擴散係數計算機斷層掃描急性不明原因的腸胃道出血小腸阻塞性疾病
外文關鍵詞:Hepatocellular carcinomaHistological gradingLiver transplantationGadoxetic-acid-enhancedhepatobiliary phaseMagnetic resonance imagingDiffusion weighted imagingApparent diffusion correlationComputed tomographyAcute gastrointestinal bleeding of obscure originsmall bowel obstruction
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醫學影像透過新的數據量測的方式,在腹部的疾病(包括肝臟及腸胃道)可以提供更早期或準確的診斷。肝細胞癌(簡稱肝癌)是全世界好發之癌症之一,每年全世界約有500,000例新增病患。 在台灣,肝癌是癌症死亡的第二大原因,平均發病年齡約50-60歲之間,若無有效治療,從有症狀出現到死亡,一般只有4~6月之久。 在大多數情況下,肝癌是一種多分級的疾病,其發生是與環境,飲食和生活方式等因素皆有關 。肝癌為一病理診斷的疾病,其危險因子包括:B型肝炎或C型肝炎感染,肝硬化,長期酗酒,有肝癌家族史,暴露於黃麴毒素。雖然傳統的肝癌病理診斷標準最近沒有改變,但肝癌的疑似病例新診斷指南於2010年已更新了新準則,完整版可在網站的美國肝病研究學會(AASLD) http://www.aasld.org/Publications/Practice Guidelines/Hepatocellular Carcinoma, Management/ HCCUpdate2010.pdf.下載。基於所述美國肝病研究學會指南, 如果病患的腹部核磁共振(MR)或電腦斷層掃描(CT)影像掃描發現有肝癌的特徵,則診斷肝癌便可不需要藉由腫瘤介入性穿刺的活體檢查。因此,若我們能藉由核磁共振影像掃描,於治療前準確預測肝癌的病理分級,則可在肝移植手術術前選定最佳的移植候選人,以得到最好的預期成果。因為肝癌組織學分化與肝移植術後患者的生存曲線是呈現正相關的,組織學分化愈差的肝癌通常生存時間愈短,肝癌組織學分化程度,同時也是術後復發的獨立預測因子。 近期的幾個國際研究團隊小組,已經觀察到肝癌病患的長期存活率,可以從肝癌病人接受局部治療或肝移植前的病理組織學分級來預測。也基於這個原因,已經有人提出了將肝癌組織學分級這個因素,當成一項重要預後因子指標,跟傳統預測肝癌預後的因素(包括有腫瘤大小範圍,腫瘤分期,或是否存在門靜脈瘤腫瘤血栓)一起考慮,用來預測或決定肝癌的治療方向。
肝移植為肝癌患者治療的方式之一,然而其術前及術後之肝臟影像評估都極其重要。早期肝移植失敗的發生率約維持在5%至10%的範圍內,並且早期肝移植失敗所代表的,通常是病患會早期死亡的關鍵原因。以前的研究已經發現:由捐肝者的特徵,包括年齡> 65歲,脂肪變性大於百分之40,病毒性肝炎呈陽性反應,術後滯留重症監護病房期間過長,和原發惡性肝腫瘤病史,均被以前的研究推定為會增加肝移植後早期的肝功能障礙的危險。在這眾多的因素當中,長時間的冷缺血時間(> 12小時),更是早已被確認為一可單獨影響早期肝移植手術成功與否的獨立危險因子。然而這些以前的研究,並沒有聚焦在研究肝移植術後的早期影像評估。在肝移植術後的早期,造成移植肝臟產生缺血再灌注的嚴重損傷,此現象與肝實質缺血性梗死的臨床和影像學特徵類似。雖然電腦斷層通常被用來評估手術後的解剖位置與併發症,但是具體的電腦斷層掃描,用於檢查結果的肝移植後的預後價值還沒有被描述。因此,我們進行了探索性研究,研究了所有肝移植術後3個月內曾接受腹部電腦斷層掃描,此影像分析將用於預測1年內可能造成的肝移植失敗。
最後,在我的腹部影像一系列論文中,同時也利用電腦斷層影像量測技術來診斷小腸疾病(包括腸道出血及小腸阻塞),我們透過成像特徵的系統分析及邏輯鑑別診斷來研究小腸疾病。雖然腸道疾病常常表現出相似的影像特點,增加相關客觀數據化的電腦斷層量測結果,可以增加診斷率並預測患者是否需要手術等積極治療。

第一目標:探討顯影劑卜邁維斯(Primovist, Gadoxetic acid)在動態肝臟核磁共振攝影與擴散權重影像的價值:研究慢性肝病的病人族群中,用於區分肝細胞癌的組織分級。
在我們的系列研究中,我們首先分析了79名肝癌患者中的141個手術切除的肝癌。對其腹部腹部核磁共振影像的信號強度做了仔細的測量,及與病理分級的關係進行了統計分析研究。卜邁維斯(Primovist, Gadoxetic acid)是一種新的核磁共振顯影劑,是一種細胞外增強T1加權影像,50%由肝膽系統代謝,50%由腎臟排泄。根據國外文獻,卜邁維斯對於偵測肝腫瘤及鑑別診斷是有幫助的,近年來因使用顯影劑注射後20分鐘的動態顯影的肝細胞相,使得動態肝臟核磁共振攝影之用途擴展到肝細胞癌之分期,以台灣肝癌為對象的研究也有同樣結果,我們之前研究已得知卜邁維斯對肝癌及分化不良的肝結節之分辨能力高 。
在我們的第一個研究中,得到的結論是,在測量核磁共振影像參數中, 動脈相的卜邁維斯顯影增強比率合併擴散權重數值,有助於術前預測肝癌的病理組織分級,研究結果發現相對減少的動脈相增強比率和低數值的擴散權重,最終肝癌的病理組織分級會較為惡性。

第二目標:確定肝臟移植後的電腦斷層影像表現,其中1年以內預測移植失敗。
然後,我們再利用電腦資料庫搜尋,評估自2007年1月至2012年12月我們醫院的一般外科所有肝移植病人。在過去的6年間,共有832成年患者(年齡大於18歲)與843肝移植(其中11例接受兩次以上肝移植)。然後與我們放射診斷部的數據資料庫(IDXRAD)交叉比對,找出哪些肝移植病人曾在換肝後3個月內,接受腹部電腦斷層攝影 。最終的病患數為198例,包括有202肝移植(其中四名患者接受重複肝移植)。在這項研究中,我們記錄了肝臟灌注缺損,肝實質均值化或有無出現低衰減區域的電腦斷層表現,同時並測量了左⁄右門靜脈的直徑與密度,與肝靜脈與下腔靜脈在吻合的直徑與密度,門靜脈周圍水腫,血腫及腹水嚴重度嚴重度(腹水被評為0 =無4=嚴重)。結果將與1年肝移植失敗做統計係數相關性之分析。我們的第二次研究旨在發現可能預測早期移植失敗的具體電腦斷層表現及數據。在我們的第二個研究中,得到的結論是,,肝移植後的最初3個月內需要做電腦斷層的患者,影像發現肝臟灌注缺損和狹小的門靜脈直徑(右門靜脈直徑小於11.5mm,左小於10.0毫米),與移植預後較差相關。這兩項參數可以預測一年內的肝臟移植失敗率。因此,手術後的對比增強電腦斷層的結果可能在未來的研究預測預後並導引正確的治療策略,提高移植成果。

第三目標:比較晚期肝癌的治療結果:立體定向放射治療(SBRT)合併及不合併使用索拉非尼 (sorafenib)
立體定向放射治療(SBRT) 在肝癌的治療準則中 ,是被不包涵在歐洲協會的治癒準則中的。值得注意的是,目前提出有關輻射引起的肝臟疾病的可能性與體外放射治療的患者,都是設定在嚴重肝硬化患者身上發生的。自從Blomgren等人通過立體定向放射治療肝腫瘤的近20年來,目前肝腫瘤用立體定向放射治療已經成為一種可被接受的方式。然而,在晚期肝細胞癌的病患中,以兩種治療(SBRT和索拉非尼)的組合療法,卻從未被研究,而且索拉非尼是否具有附加效果,也能未被進一步驗證。我們研究的目的就是比較晚期肝癌病人接受單獨接受SBRT或和索拉非尼的聯合療法的治療效果,何者較佳。
由於目前發表關於SBRT治療肝腫瘤,大多數研究都同時含有肝轉移和肝癌。關於以SBRT單獨肝細胞癌的文章仍然非常稀少。而且目前大部分的研究都是回顧性的,或者患者的數量非常有限。我們目前打算收案的病患數,為迄今最大的研究和治療的病患數。在我們的初步研究發現,儘管它的預後不良,我們的研究支持SBRT加上索拉非尼在治療晚期肝癌的效果,前6個月的50.0%(完全緩解 + 部分緩解)腫瘤反應率被證實是可行的。而且,有67%的患者的組合治療,1年生存率則是令人鼓舞的,相較於沒有合併服用索拉非尼,接受組合治療(SBRT加上索拉非尼)的患者,有顯著延長生存時間。若肝癌患者的肝功能Child-Pugh分級A和至少接受40Gy的局部輻射劑量,能達到66.67%的1年局部控制率,以及71.43%的人存活。其所觀察到的急性毒性反應也仍屬輕微。然而,局部復發仍是目前治療效果不佳的主要問題。

第四目標:使用腹部電腦斷層特徵分析預測和定位不明原因的急性胃腸道出血和腸阻塞
在患者被懷疑小腸疾病的評估,一個準確的放射檢查是很重要的。可用於識別小腸疾病和幫助可靠地記錄正常小腸的形態。小腸攝影檢查與灌腸雖早已廣泛用於小腸成像; 然而,這些檢查卻僅能能提供關於腸壁的間接信息,並且易於引起影像重疊的問題。與胃和結腸相比,小腸為急性腸出血一種罕見的位置,除非出血是塊狀,它往往是難以診斷。因此,這類患者可能因為長期慢性隱匿性失血或黑便反復發作,卻沒有一個具體的診斷。我們的研究藉由非侵入性的電腦斷層檢查,確定胃腸道出血的來源,才能改善患者的預後和需要輸血的量。雖然電腦斷層仍不及用99mTc標記的紅細胞或常規造影閃爍照相來的靈敏,但它可以是在決定採用侵入手術或血管攝影檢查前,準確的檢查出血原因及出血點的替代方案。在我們的研究中,我們發現不明原因消化道出血,可以藉由電腦斷層攝影觀察並加以評估。此外,小腸阻塞性佔所有腸阻礙病例的60-80%,由於阻塞可能造成缺血,進而引起誤診或延誤診斷,最終可能導致致命或危及生命的併發症,如腦缺血和腸穿孔。因此,患者被懷疑小腸阻塞,電腦斷層的作用是確定造成阻塞的障礙物存在或不存在,評估其嚴重程度,和現有的阻塞原因,並檢測是否有缺血的可能存在。我們的研究可以藉由電腦斷層影像發現,預測腸阻塞病患手術的必要性。
Cross-sectional imaging scan plus quantitative measurement data increases an additional value; it can provide a more accurate or early diagnosis in the field of abdominal diseases (including liver and gastrointestinal tracts). Hepatocellular carcinoma (HCC) is one of the frequently occurred cancers worldwide; each year there are around 500,000 new cases of patients. In Taiwan, HCC is the 2nd most common cause of cancer death, and it is quite malignant cancer, and the average age of onset is between about 50-60 years old. If there is no effective treatment, the duration is usually only 4 to 6 months long from the symptoms onset to death. In most cases, HCC is a multistage disease whose occurrence is linked to environmental, dietary and life-style factors. Unlike other cancers, HCC usually arises on a previously damaged organ, mostly in the setting of chronic hepatopathy, cirrhosis, or in association with hereditary diseases such as hemochromatosis, Wilson’s disease and a-1-antitrypsin deficiency. HCC is based on pathological diagnosis, and its risk factors include: HBV or HCV hepatitis carriers, liver cirrhosis, chronic alcoholism, family history, exposure to aflatoxin, and etc. Although histopathologic criteria for diagnosing classical HCC have not recently changed, new diagnostic guidelines for the suspected cases of HCC has updated in 2010. The full version of the new guidelines is available on the American Association for the Study of Liver Diseases (AASLD) website at http://www.aasld.org/Publications /Practice Guidelines/Hepatocellular Carcinoma, management/HCCUpdate2010.pdf. Based on the AASLD guidelines, biopsy is not needed for tumors with characteristic magnetic resonance (MR) or computed tomography (CT) images. Therefore, accurate pretreatment prediction of histological grade of HCCs based on MR images could aid in the identification of candidates for transplantation. Worse histological grade of HCC correlates with poor patient survival after liver transplantation and is an independent predictor of postoperative recurrence. Patients with a large low-grade hepatic tumor (well-differentiated HCC to moderately-differentiated HCC) have good survival rates after orthotopic liver transplantation, but patients with poorly-differentiated HCC have a dismal prognosis. Several groups have observed that long-term survival may be predicted from the histological grade of HCCs before local treatment or liver transplantation. For this reason, it has been suggested that prognostication and triage should ideally include histological grade along with other factors, such as tumor size, tumor stage, or the presence of portal vein tumor thrombus.
Liver transplantation is performed either from a cadaveric or living donor. The incidence of early graft failure has been reported to be in the range of 5 to 10%, and it represents the critical cause of early death following transplantation. Previous studies have shown that the donor characteristics, including age > 65 years, steatosis > 40%, positive viral hepatitis, intensive care unit stay, and history of malignancy, have been presumed to increase the risk of initial graft dysfunction. Being considered separately, prolonged cold ischemia time (>12 hours) has been recognized as an important independent risk factor for early graft failure. However, prior studies did not focus on early postoperative assessment. Occurring in the early postoperative period, graft failure represents a severe form of ischemia-reperfusion injury to the allograft, with clinical and radiographic features similar to the hepatic parenchymal infarction. Though CT is commonly used to evaluate anatomic postsurgical complications, the prognostic value of specific CT findings after liver transplantation has not been described. Therefore, we performed an exploratory study to retrospectively review all CT scans obtained within 3 months after liver transplantation to identify CT imaging findings that predict graft failure within 1 year of transplantation.
Finally, in the series of PhD study regarding abdominal images, the methodology is also applied to the small bowel imaging. CT imaging features plus quantitative measurement helps to diagnosis the gastrointestinal diseases (including obscure acute gastrointestinal bleeding and small bowel obstruction). Although intestinal diseases often exhibit similar imaging features, increasing relevant objective data of CT measurement results can increase diagnosis rate and predict whether the patient needs surgery and other active treatments.

Specific Aim 1: To investigate the value of gadoxetic acid–enhanced dynamic MRI images and DWI in differentiating the histological grades of HCC in patients with chronic liver disease.
In our serial studies, we reviewed the MR images of 79 patients with 141 surgically resected HCCs. The signal intensity and its relationship with histopathological grade were assessed. We measured the apparent diffusion correlation (ADC) values and calculated arterial enhancement ratios, washout ratios, and relative intensity ratios of HCCs relative to the surrounding liver parenchyma in gadoxetic-enhanced MR images in order to determine their relationship to the histological grade. MR imaging for liver was performed with a 1.5-T MR scanner (Philips, the Achieva) and a phased-array body coil. Turbo spin-echo (TSE) T2WI (TR/TE: 1000-1800/110; TSE factor, 24) without and with fat saturation, and coronal T2WI were obtained under respiratory trigger. Dual T1WI (TR/TE: 180-210/2.3 and 4.6; slices thickness 8mm, gap 0.8mm) and fat sat T1WIwere performed during one breath hold. Automatic shimming is used for fat suppression imaging to maximize magnetic field homogeneity.
(1) Primovist, 0.1ml/kg for patients but not used for patients less than 18 years old, injected as a bolus, through peripheral vein. Patients underwent dynamic 3D T1-weighted fast field echo (FFE) sequence (5-10/3.3; flip angle, 10°) before, using bolus tracking method for arterial and portovenous phases, about 18~20mesec and 50~55 sec after the contrast enhancement, T1WI/T1WI fat sat 3 minutes later. The postcontrast TIWI and fat sat T1WI performed at about 20 minuets after the injection.
(2) DWI sequences: Diffusion-weighted imaging was obtained with a single-shot, spin-echo echo-planar imaging sequence using a parallel technique in the axial plane, a slice thickness of 8 mm, an interslice gap of 0.8 mm, voxel size of 2.5 × 2.5 mm, the number of excitations was 4 and the b-factors=0, 100, 500, 1000 s/mm2. The motion-probing gradients with three orthogonal directions (x, y and z) were applied sequentially.
(3) The ADC value was automatically calculated by a computer program. The HCCs were identified on the T2-weighted FSE images and the contrast-enhanced T1-weighted GRE images. The ADC value of the HCC was measured on an ADC map, and the slice's location was identical to that of the selected image on the T2-weighted FSE images and the contrast-enhanced T1-weighted GRE images, respectively. The ADC mapping and eADC mapping was depicted.
In our 1st study, we concluded that the quantitative MRI parameters are benefit to predict the histological grade of HCC preoperatively, and relative decrease arterial enhancement on gadoxetic acid-enhanced MR images and low ADC are predictive of worse histological grades of HCC.
Specific Aim 2: To identify post-liver transplant CT imaging findings, which predict graft failure within 1 year.
And then, we evaluated the CT scans of 202 adult liver transplants performed who underwent CT within the first 3 months after transplantation in our 2nd study. We recorded the CT findings of liver perfusion defect, patchy liver parenchymal hypoattenuation, the diameters of the portal veins, hepatic veins, and inferior vena cava at the anastomosis, periportal edema, and hematoma. Ascites was rated as 0=none to 4=severe. Findings were correlated to graft failure within 1 year of transplantation. Our 2nd study was designed to identify specific CT findings that may predict early graft failure. We found that, for patients who have CT scans within 3 months of liver transplantation, liver perfusion defects and small portal vein diameters independently predict one-year graft failure. RPV diameters less than 11.5 mm and left less than 10.0 mm correlate with poor graft outcome.

Specific Aim 3: To compare the treatment outcome in patients with advanced HCCs: Stereotatic body radiotherapy (SBRT) with and without sorafenib administration
SBRT is not included as a curative option in the European Association for the Study of the Liver practical guidelines. Of note, concerns have been raised about the possibility of radiation-induced liver disease for patients treated with external-beam radiotherapy, which encumbered the inclusion of this kind of radiotherapy in the therapeutic strategies for cirrhotic patients. This is despite almost 20 years have now passed since Blomgren et al. have pioneered SBRT for liver malignancies. However, the value of the combination therapy of the two treatments (SBRT and sorafenib) in patients with advanced HCC was never been investigated and the additional effect of sorafenib should be further validated. The purpose of our study was to retrospectively compare the treatment outcome of patients with advanced HCC who received SBRT alone or a combined therapy with SBRT and sorafenib in a follow-up study.
Most studies published about SBRT for liver tumors have contained both liver metastases and HCC. Articles about SBRT for HCC alone are scarce. Most of these studies are retrospective, like ours, or with a very limited number of patients. We present here the largest study in terms of both patients and the number of lesions treated.
Despite its unfavorable prognosis, our study supports that SBRT is feasible in treating advanced HCC, tumor response rate of 50.0% (CR + PR) over the first 6 months. And, the 1-year overall survival rate of 67% in patients with combined therapy was encouraging. Compared to patients who did not receive sorafenib, the patients who underwent SBRT plus sorafenib had significantly prolonged survival time. While patients with a score of Child-Pugh A and those receiving doses of at least 40 Gy were able to achieved a 1-yr local control rate of 66.67% as well as 71.43% were promising. Acute toxicities were mild and tolerable. However, local and regional recurrence remained the major problem. Prospective studies of combination of SBRT with other treatment modalities may be suggested.

Specific Aim 4: To use CT features analyses for prediction and localization of obscure acute gastrointestinal bleeding and small bowel obstruction
In the evaluation of patients with suspected small-bowel disease, an accurate radiologic examination is important both for recognizing possible small-bowel disease and to help reliably document normal morphology. Small-bowel follow-through and enteroclysis are widely used for small-bowel imaging; however, these examinations provide only indirect information about the bowel wall and surrounding structures and are prone to problems caused by overlapping bowel loops.
Compared with the stomach and the colon, the small intestine is an uncommon site for intestinal bleeding, and unless the bleeding is massive, it is often difficult to diagnose. Therefore, such patients may present with prolonged, chronic occult blood loss or recurrent episodes of melena without a specific diagnosis. Although various radiologic studies have been used, a bleeding site cannot be localized in approximately 5-20% of these patients who are therefore classified with obscure gastrointestinal bleeding. Nevertheless, every effort should be made to determine the source of their gastrointestinal bleeding because adequate diagnosis is followed by an improved patient outcome and a decreased need for transfusion. Although CT is still not comparable in sensitivity to scintigraphy using 99mTc-labeled RBCs or to conventional angiography, it may be an alternative to more invasive procedures when routine workup fails to determine the cause of active intestinal bleeding. In our study, we found that obscure gastrointestinal bleeding, unexpected bleeding foci, unexpected tumors, and inflammatory bowel disease can all be easily observed on MDCT. Furthermore, the small bowel is involved in 60-80% of cases of intestinal obstruction. Because of the possibility of strangulation, misdiagnosis or delayed diagnosis can result in lethal or life-threatening complications such as ischemia and perforation. Therefore, in patients with suspected small-bowel obstruction, the role of imaging is to determine the presence or absence of an obstruction; to identify the site, severity, and cause of an existing obstruction; and to detect the possible presence of strangulation.
TABLE OF CONTENTS

ACKNOWLEDGEMENT i
CHINESE ABSTRACT iii
ENGLISH ABSTRACT ix
LIST OF FIGURES xxi
LIST OF TABLES xxii

CHAPTER 1 INTRODUCTION 1
1.1 BACKGROUND 1
1.2 DIAGNOSTIC IMAGING OF THE ABDOMEN: MRI VS. CT 1
1.2.1 Computed Tomography 1
1.2.2 Magnetic Resonance Imaging 3
1.3 CHOICE OF IMAGING TEST FOR LIVER DISEASES 4
1.3.1 Anatomy of the Liver: Couinaud Classification 6
1.3.2 The Focal Hepatic Lesion: Radiologic Assessment 9
1.3.3 Post-Liver Transplant Imaging Evaluation 11
1.4 QUANTITATIVE MEASUREMENT OF PHYSIOLOGICAL PARAMETERS 12
1.5 MOTIVATIONS AND PURPOSE 16
CHAPTER 2 HISTOLOGICAL GRADE OF HEPATOCELLULAR CARCINOMA CORRELATES WITH ARTERIAL ENHANCEMENT ON GADOXETIC ACID-ENHANCED AND DIFFUSION-WEIGHTED MR IMAGES 17
2.1 INTRODUCTION 17
2.2 MATERIAL AND METHODS 19
2.2.1 Study Population and Inclusion Criteria 19
2.2.2 MRI Protocols and Data Analysis 19
2.2.3 Clinical Data Collection and Imaging Interpretation 20
2.2.4 Statistical Analysis 27
2.3 RESULTS 28
2.3.1 Clinical and Pathological Features of the HCC Patients 28
2.3.2 Histological Grade of the HCC nodules 30
2.3.3 Relationship between Quantitative MRI Parameters and Histological Grade: Quantitative Analysis 30
2.3.4 Multivariate Stepwise Logistic Regression Data and the Cut-Off Values and Receiver Operating Characteristic Curves 33
2.4 DISCUSSION 36
2.5 CONCLUSION 39
CHAPTER 3 POST-OPERATIVE ASSESSMENT IN PATIENTS AFTER LIVER TRANSPLANTATION: IMAGING PARAMETERS ASSOCIATED WITH ONE-YEAR GRAFT FAILURE 40
3.1 INTRODUCTION 40
3.2 MATERIAL AND METHODS 41
3.2.1 Study Population and Inclusion Criteria 41
3.2.2 CT Scanning and Scan Parameters 42
3.2.3 Clinical Data Collection and Imaging Interpretation 43
3.2.4 Quantitative Measurement Method 44
3.2.5 Statistical Analysis 46
3.3 RESULTS 47
3.3.1 Demographics and Clinical Characteristics 47
3.3.2 Post-Operative Ultrasound Evaluation within 1 Week 49
3.3.3 Post-Operative CT Evaluation within 3 Months 50
3.3.4 The Receiver Operating Characteristics Curves for Cut-Off Values and Multivariate Stepwise Logistic Regression Data 53
3.3.5 Interobserver Agreements 58
3.4 DISCUSSION 61
3.5 CONCLUSION 65
CHAPTER 4 STEREOTATIC BODY RADIOTHERAPY (SBRT) WITH AND WITHOUT SORAFENIB FOR THE TREATMENT OF ADVANCED HEPATOCELLULAR CARCINOMA: COMPARISON OF THERAPEUTIC OUTCOMES IN FOLLOW-UP ANALYSES 66
4.1 INTRODUCTION 66
4.2 MATERIAL AND METHODS 67
4.2.1 Study Population and Inclusion Criteria 67
4.2.2 Treatment Schedule of SBRT and Sorafenib 68
4.2.3 Clinical Data Collection 69
4.2.4 Radiologic and Safety Evaluation 70
4.2.5 Follow-up studies 70
4.2.6 Statistical Analysis 71
4.3 RESULTS 72
4.3.1 Patient Characteristics 72
4.3.2 Laboratory Data and CT Findings Before SBRT 75
4.3.3 Tumor Response within One Year 76
4.3.4 Comparisons of the Survival Curves 77
4.4 DISCUSSION 78
4.5 CONCLUSION 79
CHAPTER 5 THE VALUE OF MULTIDETECTOR-ROW COMPUTED TOMOGRAPHY FOR LOCALIZATION OF OBSCURE ACUTE GASTROINTESTINAL BLEEDING AND SMALL BOWEL OBSTRUCTION 80
5.1 INTRODUCTION 80
5.2 MATERIALS AND METHODS 82
5.2.1 Study Population for AGIB 82
5.2.2 Patients and MDCT Image Reviewing for AGIB 82
5.2.3 Study Population in the Group of SBO 83
5.2.4 Interpretation of the MDCT Findings in Patients with SBO 84
5.3 RESULTS 89
5.3.1 Patient Characteristics and Selection of a Cut-Off Value for the Blatchford Score Using the ROC Curve in Patients with AGIB 89
5.3.2 Interobserver Agreement on CT Diagnosis, Localization of Bleeding and Signs of AGIB 93
5.3.3 MDCT Features in the Surgery and Observation Groups in Patients with SBO 94
5.3.4 Statistic Analyses of MDCT Features for Predicting Adhesion-Related SBO requiring Surgery 96
5.4 DISCUSSION 97
5.5 CONCLUSION 101
CHAPTER 6 CONCLUSION, LIMITATION, AND FUTURE EXTENSIONS 102
6.1 CONCLUSION AND SUMMARY 102
6.2 LIMITATION 103
6.3 FUTURE EXTENSIONS 105
6.3.1 RECIST and Quantitative CT of the hepatic metastatic colorectal carcinoma: Measurement of Changes related to the Treatment Outcomes 105
6.3.2 Risk Factors for Severe Complications in Patients with Orthotopic Liver Transplantation: Imaging Evaluation and Measurement of the Donor/Receipt Hepatic Vessels Differences 106
6.3.3 Comparison and Non-Ischemic and Ischemic Bowel Segments in Patients with Mesenteric Ischemia: MDCT Findings and Measurement of the Bowel-Wall Attenuation Changes 107
REFERENCES 109



LIST OF FIGURES
FIGURE 1.1 MRI IMAGING OF A HEPATIC PSEUDOLESION: FOCAL FAT-SPARING AREA 4
FIGURE 1.2 CT ANGIOGRAPHY OF THE LIVER OBTAINED BY THE MAXIMUM INTENSITY PROJECTION 5
FIGURE 1.3 SEGMENTAL ANATOMY ACCORDING TO COUINAUD CALCIFICATION 7
FIGURE 1.4 SEPARATION OF LIVER SEGMENTS ON CROSS SECTIONAL CT IMAGING 8
FIGURE 1.5 APPROACH TO FOCAL LIVER LESIONS 11
FIGURE 1.6 CURRENT AND EVOLVING ONCOLOGIC IMAGING BIOMARKERS 14
FIGURE 1.7 SOFTWARE FOR CT PERFUSION TO MEASURE THE HEMODYNAMIC CHANGES OF THE LIVER 15
FIGURE 2.1 THE SIGNAL INTENSITY OF HCC TUMOR BY PLACING THE REGIONS OF INTEREST 23
FIGURE 2.2 RELATIONSHIP BETWEEN THE QUANTITATIVE PARAMETERS AND THE HISTOLOGICAL GRADE OF HCC 32
FIGURE 2.3 RECEIVER OPERATING CHARACTERISTIC CURVES OF THE MRI PARAMETERS IN DIFFERENTIATING HISTOLOGICAL GRADE OF HCC 34
FIGURE 3.1 MEASUREMENT OF THE SHORT-AXIS DIAMETER OF THE RPV AND LPV 45
FIGURE 3.2 ROC CURVES FOR CUT-OFF VALUES AND AUC: RPV, LPV AND IVC 53
FIGURE 3.3 A LIVER-TRANSPLANT PATIENT WITH THE TYPICAL CT APPEARANCE OF GRAFT FAILURE 55
FIGURE 3.4 THE KAPLAN-MEIER METHOD AND COX PROPORTIONAL HAZARD REGRESSION MODEL FOR THE 3 INDEPENDENT PARAMETERS 57
FIGURE 3.5 BLAND-ALTMAN DIFFERENCE PLOTS FOR DIAMETER MEASUREMENT 60
FIGURE 3.6 BLAND-ALTMAN DIFFERENCE PLOTS FOR ATTENUATION MEASUREMENT 61
FIGURE 4.1 PATIENT FLOWCHART 68
FIGURE 4.2 HISTORY OF PREVIOUS TREATMENT: RADIOFREQUENCY (RFA) OR TRANSARTERIAL CHEMO-EMBOLIZATION (TACE) 73
FIGURE 4.3 SURVIVAL CURVE COMPARISON 78
FIGURE 5.1 THREE DEGREES OF SBO DEFINED BY MDCT IMAGES 85
FIGURE 5.2 SMALL BOWEL FECES SIGN 86
FIGURE 5.3 CLOSED-LOOP SIGN 87
FIGURE 5.4 THE “WHIRL” SIGN 88
FIGURE 5.5 GRAPH SHOWED THE RESULTS OF THE ROC CURVE OF BLATCHFORD SCORING SYSTEM IN MDCT DIAGNOSIS OF AGIB 91
FIGURE 5.6 ROC CURVE OF THE BLATCHFORD SCORES VERSUS MDCT DIAGNOSIS AND SURGICAL FINDINGS OF OBSCURE AGIB 92





LIST OF TABLES
TABLE 2.1 CLINICAL CHARACTERISTICS AND PATHOLOGICAL BACKGROUND OF 79 PATIENTS WITH 141 HCC NODULES CATEGORIZED BY CHILD-PUGH CLASSIFICATION 29
TABLE 2.2 MORPHOLOGICAL FEATURES OF THE 141 HCC NODULES CATEGORIZED BY HISTOLOGICAL GRADING 31
TABLE 2.3 MULTIVARIABLE STEPWISE LOGISTIC REGRESSION ANALYSES OF THE FIVE MRI PARAMETERS TO PREDICT NON-WHCC 33
TABLE 2.4 CUT-OFF VALUES, SENSITIVITY, SPECIFICITY, AND THE AUC DETERMINED BY ROC ANALYSIS 36
TABLE 3.1 DEMOGRAPHICS AND CLINICAL CHARACTERISTICS IN PATIENTS AFTER TRANSPLANTATION 48
TABLE 3.2 US FINDINGS WITHIN 1 WEEK AFTER TRANSPLANTATION 50
TABLE 3.3 CT FINDINGS WITHIN 3 MONTHS AFTER TRANSPLANTATION 52
TABLE 3.4 UNIVARIATE AND MULTIVARIATE LOGISTIC REGRESSION FOR THE SIGNIFICANT PARAMETERS 54
TABLE 3.5 COX PROPORTIONAL REGRESSION MODEL FOR THE INDEPENDENT PARAMETERS 56
TABLE 3.6 INTER-OBSERVER VARIABILITY AGREEMENTS FOR THE NOMINAL AND QUANTITATIVE MDCT MEASUREMENTS 59
TABLE 4.1 DEMOGRAPHIC DATA OF THE 66 PATIENTS WITH HCC BEFORE TREATMENT 74
TABLE 4.2 LABORATORY DATA AND CT FINDINGS BEFORE RECEIVING THERAPY 76
TABLE 4.3 SERIAL FOLLOW-UP CT STUDIES AT 3-MONTH, 6-MONTH AND 12-MONTH PERIOD 77
TABLE 5.1 DEMOGRAPHICS AND CLINICAL INFORMATION OF PATIENTS WITH AGIB 90
TABLE 5.2 INTEROBSERVER AGREEMENTS AMONG OBSERVERS FOR DIAGNOSIS OF AGIB WITH MDCT SIGNS 93
TABLE 5.3 COMPARISON OF CLINICAL AND LABORATORY PARAMETERS IN THE SURGERY AND OBSERVATION GROUPS 95
TABLE 5.4 SENSITIVITY, SPECIFICITY, ACCURACY VALUES AND ODDS RATIO OF MDCT FEATURES FOR PREDICTING ADHESION-RELATED SBO REQUIRING SURGERY 97
TABLE 5.5 NUMBER OF PATIENTS WHO WOULD BE IDENTIFIED BY USING COMBINATIONS OF MDCT FINDINGS TO PREDICT ADHESION-RELATED SBO PATIENTS REQUIRING SURGERY 97
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