Published online before print September 27, 2006, 10.1148/radiol.2412051209
(Radiology 2006;241:581-588.)
© RSNA, 2006
Vascular and Interventional Radiology |
Diaphragmatic Weakness after Transcatheter Arterial Chemoembolization of Inferior Phrenic Artery for Treatment of Hepatocellular Carcinoma1
Sung Wook Shin, MD,
Young Soo Do, MD,
Sung Wook Choo, MD,
Wei Chiang Lieu, MD,
Sung Ki Cho, MD,
Kwang Bo Park, MD,
Byung Chul Yoo, MD,
Eun Hae Kang, MD and
In-Wook Choo, MD
1 From the Department of Radiology and Center for Imaging Sciences (S.W.S., Y.S.D., S.W.C., W.C.L., S.K.C., K.B.P., I.W.C.), Division of Gastroenterology (B.C.Y.), and Department of Medicine, Division of Pulmonary and Critical Care Medicine (E.H.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea. Received July 19, 2005; revision requested September 22; revision received October 19; accepted November 17; final version accepted January 2, 2006.
Address correspondence to Y.S.D. (e-mail: ysdo{at}smc.samsung.co.kr).
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ABSTRACT
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Purpose: To prospectively assess the diaphragmatic anatomic and functional consequences of transcatheter arterial chemoembolization (TACE) of the inferior phrenic artery in patients with hepatocellular carcinoma.
Materials and Methods: Informed consent and institutional review board approval were obtained. Fifteen patients (13 men, two women; mean age, 52 years; age range, 22–61 years) who underwent TACE of the inferior phrenic artery for treatment of hepatocellular carcinoma were enrolled. The right inferior phrenic artery was embolized in 14 patients, and the left inferior phrenic artery was embolized in one patient. Chest radiography, fluoroscopy, computed tomography (CT), and pulmonary function tests were performed before and after TACE of the inferior phrenic artery. The post-TACE examinations were performed 2–3 months after TACE, and the results were compared with those of the pre-TACE examinations. A paired t test or the Wilcoxon signed rank test was used for statistical analyses.
Results: At chest radiography and fluoroscopy, six of 15 patients (40%) had both elevation and movement abnormality of the ipsilateral hemidiaphragm after TACE of the inferior phrenic artery. The mean (± standard deviation) diaphragmatic thickness on CT scans changed from 9.11 mm ± 3.02 to 7.67 mm ± 2.27 after TACE (P = .048). The mean vital capacity also was significantly decreased after TACE, from 91.87% ± 18.52 to 82.27% ± 16.94 of the predicted value (P = .006). The decreases in diaphragmatic thickness and vital capacity were most pronounced in the patients with abnormal findings at chest radiography and fluoroscopy.
Conclusion: After TACE of the inferior phrenic artery, a substantial portion of patients showed functional and anatomic evidence of diaphragmatic weakness.
© RSNA, 2006
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INTRODUCTION
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Transcatheter arterial chemoembolization (TACE) performed with a mixture of various anticancer agents and iodized oil has become widely accepted as a palliative procedure or even as an alternative to surgical resection for the treatment of hepatocellular carcinoma (HCC) (1–5). When the hepatic artery becomes occluded as a consequence of performing repetitive TACE procedures on the hepatic artery, extrahepatic collateral pathways that supply the HCC can develop (6,7). If the HCC is large or is located adjacent to the hepatic ligaments or the bare area, extrahepatic parasitic blood supplies may be present despite the patency of the hepatic artery (8–10). Extrahepatic collateral pathways or parasitic blood supplies to the HCC can decrease the therapeutic efficacy of TACE of the hepatic artery, and additional TACE procedures to address these extrahepatic supplies to the HCC should be performed to effectively control the cancer (6,8,11).
The inferior phrenic artery (IPA) is one of the most common extrahepatic collateral pathways that can supply HCC. TACE of the IPA has been reported to have its own therapeutic role as an adjunct to TACE of the hepatic artery, and this can be done without causing serious procedural complications. A few minor complications may occur, such as shoulder pain, a small amount of pleural effusion, basal atelectasis, transient mild hemoptysis, and hiccup (8,11,12). However, because the IPA is one of the major arteries supplying blood to the diaphragm, TACE of this artery may induce diaphragmatic injury and dysfunction. One of the patients seen at our institution, for example, showed paradoxical movement of the diaphragm after TACE of the IPA was performed. A few authors have reported the possibility of diaphragmatic injury after TACE of the IPA or internal mammary artery (8,10,11). However, to the best of our knowledge, there had been no published work focusing on diaphragmatic injury induced by a TACE procedure. Thus, the purpose of our study was to prospectively assess the diaphragmatic anatomic and functional consequences of TACE of the IPA in patients with HCC.
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MATERIALS AND METHODS
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Patients
Our study had institutional review board approval, and informed consent was obtained from all patients. We prospectively selected patients whose HCCs had a high possibility of being supplied by the IPA according to findings at computed tomography (CT). Such findings included a peripheral area of a tumor with no iodized oil retention, further growth of a tumor at the diaphragmatic aspect after previous TACE of the hepatic artery, or a large tumor abutting the diaphragm with visualization of the hypertrophied IPA (8,13). Those patients who had previously undergone TACE of the IPA were excluded from the study. Patients with any pleuropulmonary or chest wall abnormality also were excluded to rule out the possibility of underlying restrictive lung disease. Thus, from April 2002 through March 2003, 20 patients were initially enrolled. They then underwent pre-TACE examinations followed by the scheduled TACE procedures. However, five patients were excluded because no tumor staining was noted on the IPA arteriograms that were obtained during the TACE procedures; as a result, these patients did not undergo TACE of the IPA. Therefore, 15 patients were included in our study (13 men, two women; mean age, 52 years; age range, 22–61 years). All patients had underlying cirrhosis (related to hepatitis B virus in 14 and hepatitis C virus in one).
Imaging findings at CT and arteriography in all patients were consistent with HCC. In addition to the imaging findings, the diagnosis of HCC was based on the following criteria in some patients: surgical findings in two patients, biopsy results in three, elevated 
-fetoprotein levels (>400 µg/L) in six, and clinical findings (eg, liver cirrhosis or hepatitis) in four. Selective arteriography of the IPA depicted a parasitic arterial supply to the HCC in all patients. In three patients, TACE of the IPA was performed at the first session of concomitant TACE of the hepatic artery. The other 12 patients had previously undergone one to eight sessions of TACE of the hepatic artery, the other extrahepatic parasitic feeders, or both. TACE of the right IPA was performed in 14 patients, and TACE of the left IPA was performed in one patient; only one IPA was embolized in each patient. The right IPA originated from the celiac trunk in three patients, directly from the aorta in four, and from the right renal artery in seven. The one left IPA originated from the celiac trunk. The liver segments that contained most of the tumor that was fed by the IPA were segments VII (n = 8), VI (n = 3), I (n = 2), VIII (n = 1), and II (the left IPA, n = 1). The two HCCs in segment I were growing exophytically and abutting the diaphragm.
TACE Technique
After catheterization of the orifice of the IPA with a 5-F Yashiro catheter (Terumo, Tokyo, Japan) or a Michaelson catheter (Cook, Bloomington, Ind), selective arteriography of the IPA was performed with the digital subtraction technique to determine the presence of tumor staining and any tumor neovascularity. Then, a coaxial microcatheter (Microferret; Cook) was inserted into the mid-portion or, if possible, the distal portion of the IPA. TACE of the IPA was performed through the microcatheter with transarterial infusion of a mixture of iodized oil (Lipiodol; Andre Guerbet, Aulnay-sous-Bois, France) and doxorubicin hydrochloride (Adriamycin; Dong-A Pharm, Seoul, Korea) by three interventional radiologists (S.W.S., Y.S.D., S.W.C.) with 4, 14, and 11 years of experience in TACE of HCC, respectively. The mixture of iodized oil and doxorubicin hydrochloride was emulsified by means of vigorous pumping 10–20 times between two syringes that were interconnected with a three-way stopcock. The doses of iodized oil and doxorubicin hydrochloride depended on the size and vascularity of the tumor. The actual infused doses were 2–15 mL of iodized oil (mean dose, 4 mL) and 5–40 mg (mean dose, 16 mg) of doxorubicin hydrochloride.
Thirteen patients underwent additional embolization of the IPA with gelatin sponge pledgets (Cutanplast; Mascia Brunelli, Milan, Italy) 1–2 mm in diameter because use of iodized oil embolization alone was observed to be insufficient for blockage of the IPA. The end point of TACE was observation of a compact uptake of iodized oil within the stained tumor or notation of stagnation of the blood flow of the IPA. We infused 3–10 mL of 1%—2% lidocaine through the microcatheter to control pain during or at the end of the procedure as needed.
Pre- and Post-TACE Evaluation and Patient Groups
Chest radiography, fluoroscopy, CT, and pulmonary function tests were performed in all patients before and after TACE of the IPA. Post-TACE examinations were performed 2–3 months after the TACE procedures, either during admission for subsequent TACE or in the outpatient department. Two radiologists (W.C.L., S.K.C.), each with 4 years of experience interpreting chest radiographs and fluoroscopic images of the chest, performed chest radiography and fluoroscopy for consensus evaluation of elevation of the diaphragm and abnormal diaphragmatic movement (paradoxical or decreased movement) that might have developed after TACE of the IPA. We considered the diaphragm to be elevated if there was elevation of the dome of at least 2 cm compared with the height of the dome on the pre-TACE chest radiograph.
CT was performed with helical CT scanners (HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis) according to the three-phase liver CT protocol used in our hospital: a delay of 30 seconds for the hepatic arterial phase, a delay of 60 seconds for the portal venous phase, and a delay of 90 seconds for the equilibrium phase after the start of infusion of the intravenous contrast medium (Iopamiron 300; Bracco, Milan, Italy). With CT, we measured the maximal short-axis thickness of the diaphragm at the crural portion and the comparable sectional images of the same level in each patient. All of the measurements were made with an electronic caliper on a picture archiving and communication system monitor (Pathspeed, version 8.1; GE Medical Systems Integrated Imaging Solutions, Mt Prospect, Ill). The thickness of the contralateral diaphragm (the nonembolized side) was measured in the same manner. Measurements of the diaphragmatic thickness were independently made by two radiologists (W.C.L., S.K.C.), each with 4 years of experience interpreting chest CT images, and the final measurement was derived by averaging the two independent measurements. Basal atelectasis and pleural effusion were also evaluated as present or not present (W.C.L., S.K.C.).
Pulmonary function tests were performed with spirometry to estimate vital capacity, forced expiratory volume in 1 second–forced vital capacity ratio, total lung capacity, residual volume, and functional residual capacity. The results of pulmonary function tests were interpreted by a physician (E.H.K.) with 4 years of experience interpreting such results. The patients were questioned (by S.W.S.) as to whether they had developed any symptoms, such as shoulder pain or dyspnea on exertion, after TACE of the IPA.
We judged the diaphragm to be weakened if it was elevated at chest radiography and if paradoxical or decreased movement was present at fluoroscopy (14). The patients were then divided into two groups according to the presence (group 1) or absence (group 2) of diaphragmatic weakness after TACE of the IPA.
Statistical Analysis
Statistical analyses were performed with commercially available software (SPSS, version 11.5; SPSS, Chicago, Ill). A paired t test or the Wilcoxon signed rank test was used to compare the diaphragmatic thickness and the pulmonary function test results that were measured before and after TACE. Before performing the t test, we used the Shapiro-Wilk test to determine whether the normality assumption was met. A two-tailed P value of less than .05 was considered to indicate a significant difference.
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RESULTS
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Chest Radiography, Fluoroscopy, and Patient Groups
TACE of the IPA was performed for treatment of HCC in 15 patients (Fig 1). After TACE, six patients showed both elevation and paradoxical or decreased movements of their ipsilateral hemidiaphragms at chest radiography and fluoroscopy (Fig 2). One additional patient showed only paradoxical movement of the diaphragm, and this was not considered to be diaphragmatic weakness (14). Thus, the six (40%) patients who had abnormalities at both chest radiography and fluoroscopy were in group 1; the other nine patients were in group 2.
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Figure 1a: Images in 59-year-old man with HCC. (a) Transverse arterial phase CT image shows peripheral area of tumor (arrows), with no iodized oil retention within the liver segment VIII abutting the diaphragm. (b) Posteroanterior selective arteriogram of the right IPA. This portion of the tumor (arrows) was noted to be supplied by the right IPA. (c) Transverse arterial phase CT image obtained 3 months after TACE of the IPA shows compact retention (arrows) of iodized oil within the tumor.
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Figure 1b: Images in 59-year-old man with HCC. (a) Transverse arterial phase CT image shows peripheral area of tumor (arrows), with no iodized oil retention within the liver segment VIII abutting the diaphragm. (b) Posteroanterior selective arteriogram of the right IPA. This portion of the tumor (arrows) was noted to be supplied by the right IPA. (c) Transverse arterial phase CT image obtained 3 months after TACE of the IPA shows compact retention (arrows) of iodized oil within the tumor.
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Figure 1c: Images in 59-year-old man with HCC. (a) Transverse arterial phase CT image shows peripheral area of tumor (arrows), with no iodized oil retention within the liver segment VIII abutting the diaphragm. (b) Posteroanterior selective arteriogram of the right IPA. This portion of the tumor (arrows) was noted to be supplied by the right IPA. (c) Transverse arterial phase CT image obtained 3 months after TACE of the IPA shows compact retention (arrows) of iodized oil within the tumor.
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Figure 2a: Images in 52-year-old man with HCC. (a) Posteroanterior chest radiograph obtained before TACE of the right IPA shows no abnormality. (b) Posteroanterior chest radiograph obtained 2 months after TACE shows elevation of the right hemidiaphragm and compensatory hyperinflation of the left lung, along with linear atelectasis in the right lung base. (c) Expiratory and (d) inspiratory supine posteroanterior fluoroscopic images obtained 2 months after TACE of the IPA show markedly decreased movement of the right hemidiaphragm.
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Figure 2b: Images in 52-year-old man with HCC. (a) Posteroanterior chest radiograph obtained before TACE of the right IPA shows no abnormality. (b) Posteroanterior chest radiograph obtained 2 months after TACE shows elevation of the right hemidiaphragm and compensatory hyperinflation of the left lung, along with linear atelectasis in the right lung base. (c) Expiratory and (d) inspiratory supine posteroanterior fluoroscopic images obtained 2 months after TACE of the IPA show markedly decreased movement of the right hemidiaphragm.
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Figure 2c: Images in 52-year-old man with HCC. (a) Posteroanterior chest radiograph obtained before TACE of the right IPA shows no abnormality. (b) Posteroanterior chest radiograph obtained 2 months after TACE shows elevation of the right hemidiaphragm and compensatory hyperinflation of the left lung, along with linear atelectasis in the right lung base. (c) Expiratory and (d) inspiratory supine posteroanterior fluoroscopic images obtained 2 months after TACE of the IPA show markedly decreased movement of the right hemidiaphragm.
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Figure 2d: Images in 52-year-old man with HCC. (a) Posteroanterior chest radiograph obtained before TACE of the right IPA shows no abnormality. (b) Posteroanterior chest radiograph obtained 2 months after TACE shows elevation of the right hemidiaphragm and compensatory hyperinflation of the left lung, along with linear atelectasis in the right lung base. (c) Expiratory and (d) inspiratory supine posteroanterior fluoroscopic images obtained 2 months after TACE of the IPA show markedly decreased movement of the right hemidiaphragm.
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CT Findings
The mean (± standard deviation) thickness of the diaphragm at the crural portion was 9.11 mm ± 3.02 before TACE of the IPA and 7.67 mm ± 2.27 after TACE; this difference was significant (P = .048) (Fig 3). In group 1, the mean thickness of the diaphragm changed from 9.53 mm ± 4.36 to 6.32 mm ± 1.81 after TACE (P = .034). In group 2, the mean thickness of the diaphragm was 8.82 mm ± 1.95 before TACE and 8.57 mm ± 2.17 mm after TACE (P = .305). The thickness of the hemidiaphragm contralateral to the embolized IPA showed no substantial change after TACE (Table 1). Additional findings seen at CT were minimal basal atelectasis in 10 patients and a small amount of pleural effusion in three patients.
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Figure 3a: Transverse portal venous phase CT images in 60-year-old man with HCC obtained (a, b) before and (c, d) after TACE of the IPA. (a, b) Scans obtained at the level of the celiac trunk (a) and the superior mesenteric artery (b) show thick appearance (arrowheads) of the crural portion of the right hemidiaphragm. (c, d) Scans obtained at the level of the celiac trunk (c) and the superior mesenteric artery (d) 2 months after TACE of the IPA show diffuse thinning (arrowheads) of the right hemidiaphragm. The scanned levels appear somewhat different from those on the pre-TACE CT scans owing to the elevation of the right diaphragm and compensatory overinflation of the left diaphragm. The crural portion of the left hemidiaphragm shows no definite change.
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Figure 3b: Transverse portal venous phase CT images in 60-year-old man with HCC obtained (a, b) before and (c, d) after TACE of the IPA. (a, b) Scans obtained at the level of the celiac trunk (a) and the superior mesenteric artery (b) show thick appearance (arrowheads) of the crural portion of the right hemidiaphragm. (c, d) Scans obtained at the level of the celiac trunk (c) and the superior mesenteric artery (d) 2 months after TACE of the IPA show diffuse thinning (arrowheads) of the right hemidiaphragm. The scanned levels appear somewhat different from those on the pre-TACE CT scans owing to the elevation of the right diaphragm and compensatory overinflation of the left diaphragm. The crural portion of the left hemidiaphragm shows no definite change.
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Figure 3c: Transverse portal venous phase CT images in 60-year-old man with HCC obtained (a, b) before and (c, d) after TACE of the IPA. (a, b) Scans obtained at the level of the celiac trunk (a) and the superior mesenteric artery (b) show thick appearance (arrowheads) of the crural portion of the right hemidiaphragm. (c, d) Scans obtained at the level of the celiac trunk (c) and the superior mesenteric artery (d) 2 months after TACE of the IPA show diffuse thinning (arrowheads) of the right hemidiaphragm. The scanned levels appear somewhat different from those on the pre-TACE CT scans owing to the elevation of the right diaphragm and compensatory overinflation of the left diaphragm. The crural portion of the left hemidiaphragm shows no definite change.
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Figure 3d: Transverse portal venous phase CT images in 60-year-old man with HCC obtained (a, b) before and (c, d) after TACE of the IPA. (a, b) Scans obtained at the level of the celiac trunk (a) and the superior mesenteric artery (b) show thick appearance (arrowheads) of the crural portion of the right hemidiaphragm. (c, d) Scans obtained at the level of the celiac trunk (c) and the superior mesenteric artery (d) 2 months after TACE of the IPA show diffuse thinning (arrowheads) of the right hemidiaphragm. The scanned levels appear somewhat different from those on the pre-TACE CT scans owing to the elevation of the right diaphragm and compensatory overinflation of the left diaphragm. The crural portion of the left hemidiaphragm shows no definite change.
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Results of Pulmonary Function Tests
At pulmonary function testing, there was a significant change in mean vital capacity after TACE of the IPA in all patients, from 91.87% ± 18.52 to 82.27% ± 16.94 of the predicted value (P = .006). In group 1, mean vital capacity changed from 92.83% ± 21.30 of the predicted value before TACE to 72.83% ± 14.50 of the predicted value after TACE (P = .011). In group 2, the respective mean values were 91.22% ± 17.75 and 87.89% ± 16.80 (P = .090). Total lung capacity slightly decreased after TACE, but this finding did not reach statistical significance for any patient or either group. The other pulmonary function test results also showed no substantial change after TACE (Table 2).
Clinical Findings
Twelve patients reported having shoulder pain, and three reported having mild dyspnea on exertion after TACE of the IPA. All patients who had noted dyspnea were in group 1, and they had undergone gelatin sponge embolization in addition to iodized oil embolization. However, these symptoms gradually resolved within a few weeks after the procedure, and none of these patients reported any symptoms at the follow-up examinations. During the follow-up period, no events that may have affected diaphragmatic function occurred in any patients.
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DISCUSSION
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TACE may lead to typical ischemic complications, including tissue injury and even necrosis (9,15–17). When considering the diaphragmatic blood supply of the IPA, it can be inferred that TACE of the IPA may injure the diaphragm and thus affect the inspiratory function of the diaphragm. A few authors (8,10,11) have previously mentioned the possibility of diaphragmatic injury after TACE of the IPA or the internal mammary artery.
Because we did not perform electromyography, the diagnosis of diaphragmatic weakness was based on findings at chest radiography and fluoroscopy. In our study, abnormalities were seen in six (40%) of the 15 patients both at chest radiography and fluoroscopy after TACE of the IPA. Chest radiography and fluoroscopy are problematic for the diagnosis of diaphragmatic weakness because of their appreciable false-positive and false-negative rates (18,19). Despite these considerations, we believe that our observations were valid because we compared our post-TACE findings with the findings of the baseline studies performed before TACE; the latter findings were normal in all our patients.
It has been shown that with unilateral diaphragmatic paralysis, pulmonary function tests typically reveal a mild restrictive pattern; total lung capacity is about 85% of predicted value, vital capacity is reduced to about 75% of the predicted value, and functional residual capacity and forced expiratory volume in 1 second–forced vital capacity ratio are usually normal (19,20). A decrease in vital capacity in the absence of lung disease is the simplest indication of inspiratory muscle weakness (21). In our study, there was a significant change in vital capacity, from 91.87% to 82.27% of the predicted value after TACE of the IPA. The decrease in vital capacity was most pronounced in group 1, and the other pulmonary function test results did not significantly change. We believe that these pulmonary function test results reflect a tendency toward a restrictive pulmonary function test pattern, which can be attributed to diaphragmatic weakness after TACE of the IPA. The reason that our pulmonary function test measurements did not reach the values mentioned earlier in this paragraph may be that TACE of the IPA caused only diaphragmatic weakness and not diaphragmatic paralysis.
With paralysis or disuse, a muscle undergoes structural changes that result in a reduction of its cross-sectional area (22). We observed a decrease in diaphragmatic thickness after TACE of the IPA, which was most pronounced in group 1; the diaphragm contralateral to the embolized IPA showed no substantial change in its thickness. It has been reported that with ultrasonography (US), the paralyzed diaphragm is notably thinner than the normally functioning diaphragm (14). With US, the diaphragmatic thickness was measured at the zone of apposition of the diaphragm to the rib cage through an intercostal space between the anteroaxillary and midaxillary lines (14,23). Our CT measurements were somewhat different: They were made at the crural portion of the diaphragm, mainly because the zone of apposition was barely discernible on CT scans (24,25). Despite these differences, we believe that both CT and US can be used to measure the diaphragmatic thickness and predict its functional status in relation to its cross-sectional area. In our study, the diaphragmatic crura became thin after TACE of the IPA. From our functional and anatomic findings, we conclude that TACE of the IPA can induce ipsilateral diaphragmatic weakness and that this is probably caused by ischemic damage due to occlusion of the feeding artery after TACE and muscle necrosis exerted by the infusion of a toxic anticancer agent. However, we acknowledge that we had no histopathologic proof in our study.
The diaphragm receives its blood supply from multiple systemic arteries, including the IPA, the internal mammary artery, and the intercostal arteries. These arteries anastomose to form arterial circles around the central tendon and the insertion of the diaphragm, and this diversity of blood supply may be an important factor in the diaphragm's resistance to fatigue and ischemia (11,26). Despite the collateral arterial supply to the diaphragm, we believe that the liquid chemoembolic agent used in the TACE procedure (basically composed of iodized oil and a dissolved anticancer drug) may travel far peripherally to approach the anastomotic point of the various collateral arteries. This results in interruption of the potential collateral pathways through which the collateral arteries of the diaphragm can supply the portion of the diaphragm being supplied by the occluded arteries; ischemic damage then occurs. The occurrence of diaphragmatic weakness in some but not all of our patients may be partly explained by the status of the collateral supply to the diaphragm and the extent of the embolization procedure, which could have been different in each patient. TACE of the IPA may have a greater preferential effect on the crural portion of the diaphragm that the branches of the IPA directly supply.
Unilateral diaphragmatic weakness is frequently asymptomatic. It can also produce mild respiratory dysfunction and minimal symptoms, due mostly to the compensatory function of the intact contralateral diaphragm and accessory inspiratory muscles (20,21,27). This mechanism may explain why only a few patients in our study reported having mild dyspnea.
Our study had limitations: First, prediction of the extrahepatic supply from the IPA to the HCC is difficult, and our study involved a small patient cohort. Because of this, it may be difficult to draw a concrete conclusion from our study findings. Second, because we did not include a control group of patients undergoing hepatic artery TACE but not TACE of the IPA, it may appear that the diaphragmatic weakness was not causally related to the TACE of the IPA per se. However, our study was self-controlled because we compared pre- and post-TACE findings. We think that to create a true control group, the patients in the control group should have HCC supplied from the IPA; in such patients, it would be unethical not to treat the HCC (ie, not to perform embolization).
Third, the basal atelectasis and the resultant reduction in lung compliance may have influenced the pulmonary function test measurements. We did not evaluate this in detail for our patients because basal atelectasis can result from diaphragmatic weakness, its degree was minimal in our patients, and its effect on pulmonary function tests is very difficult to objectively measure. Fourth, we do not know the long-term results of TACE of the IPA; as the symptoms improved with time in three of our patients, the observed diaphragmatic weakness may be only a temporary phenomenon. However, it may also be permanent, with other mechanisms compensating for its effect on the respiratory function.
In conclusion, after TACE of the IPA, a substantial portion of patients showed abnormal movement and thinning of the diaphragm, along with a decrease in their vital capacity, and these findings may reflect diaphragmatic weakness. Although the clinical implication of this functional derangement of the diaphragm is not clear—there were only a few symptomatic patients in our study—TACE of the IPA should be performed as cautiously and selectively as possible, especially in patients with preexisting contralateral diaphragmatic dysfunction or pulmonary disease.
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ADVANCES IN KNOWLEDGE
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- After transcatheter arterial chemoembolization of the inferior phrenic artery, the diaphragm can show abnormal movement and elevation and can become thin.
- After transcatheter arterial chemoembolization of the inferior phrenic artery, pulmonary function tests can reveal a mild restrictive pattern.
- Transcatheter arterial chemoembolization of the inferior phrenic artery can induce diaphragmatic weakness.
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FOOTNOTES
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Abbreviations: HCC = hepatocellular carcinoma • IPA = inferior phrenic artery • TACE = transcatheter arterial chemoembolization
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, S.W.S., Y.S.D.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, S.W.S., W.C.L., S.K.C., K.B.P., B.C.Y., E.H.K., I.W.C.; clinical studies, S.W.S., Y.S.D., S.W.C., E.H.K.; statistical analysis, S.W.S.; and manuscript editing, all authors
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References
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- Choi BI, Kim HC, Han JK, et al. Therapeutic effect of transcatheter oily chemoembolization therapy for encapsulated nodular hepatocellular carcinoma: CT and pathologic findings. Radiology 1992;182:709–713.[Abstract/Free Full Text]
- Park JH, Han JK, Chung JW, Han MC, Kim ST. Postoperative recurrence of hepatocellular carcinoma: results of transcatheter arterial chemoembolization. Cardiovasc Intervent Radiol 1993;16:21–24.[Medline]
- Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K, Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 1983;148:397–401.[Abstract/Free Full Text]
- Uchida H, Ohishi H, Matsuo N, et al. Transcatheter hepatic segmental arterial embolization using lipiodol mixed with an anticancer drug and Gelfoam particles for hepatocellular carcinoma. Cardiovasc Intervent Radiol 1990;13:140–145.[Medline]
- Matsui O, Kadoya M, Yoshikawa J, et al. Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization. Radiology 1993;188:79–83.[Abstract/Free Full Text]
- Soo CS, Chuang VP, Wallace S, Charnsangavej C, Carrasco H, Bowers T. Treatment of hepatic neoplasm through extrahepatic collaterals. Radiology 1983;147:45–49.[Abstract/Free Full Text]
- Charnsangavej C, Chuang VP, Wallace S, Soo CS, Bowers T. Angiographic classification of hepatic arterial collaterals. Radiology 1982;144:485–494.[Abstract/Free Full Text]
- Chung JW, Park JH, Han JK, Choi BI, Kim TK, Han MC. Transcatheter oily chemoembolization of the inferior phrenic artery in hepatocellular carcinoma: the safety and potential therapeutic role. J Vasc Interv Radiol 1998;9:495–500.[Medline]
- Park SI, Lee do Y, Won JY, Lee JT. Extrahepatic collateral supply of hepatocellular carcinoma by the intercostal arteries. J Vasc Interv Radiol 2003;14:461–468.[Medline]
- Nakai M, Sato M, Kawai N, et al. Hepatocellular carcinoma: involvement of the internal mammary artery. Radiology 2001;219:147–152.[Abstract/Free Full Text]
- Duprat G, Charnsangavej C, Wallace S, Carrasco CH. Inferior phrenic artery embolization in the treatment of hepatic neoplasms. Acta Radiol 1988;29:427–429.[Medline]
- Tajima T, Honda H, Kuroiwa T, et al. Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer. J Vasc Interv Radiol 2002;13:893–900.[Medline]
- Okino Y, Kiyosue H, Matsumoto S, Takaji R, Yamada Y, Mori H. Hepatocellular carcinoma: prediction of blood supply from right inferior phrenic artery by multiphasic CT. J Comput Assist Tomogr 2003;27:341–346.[CrossRef][Medline]
- Gottesman E, McCool FD. Ultrasound evaluation of the paralyzed diaphragm. Am J Respir Crit Care Med 1997;155:1570–1574.[Abstract]
- Hemingway AP, Allison DJ. Complications of embolization: analysis of 410 procedures. Radiology 1988;166:669–672.[Abstract/Free Full Text]
- Chung JW, Park JH, Han JK, et al. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996;198:33–40.[Abstract/Free Full Text]
- Kovacs AF, Turowski B. Chemoembolization of oral and oropharyngeal cancer using a high-dose cisplatin crystal suspension and degradable starch microspheres. Oral Oncol 2002;38:87–95.[CrossRef][Medline]
- Alexander C. Diaphragm movements and the diagnosis of diaphragmatic paralysis. Clin Radiol 1966;17:79–83.[CrossRef][Medline]
- Arborelius M Jr, Lilja B, Senyk J. Regional and total lung function studies in patients with hemidiaphragmatic paralysis. Respiration 1975;32:253–264.[Medline]
- Ridyard JB, Stewart RM. Regional lung function in unilateral diaphragmatic paralysis. Thorax 1976;31:438–442.[Abstract]
- Fitting JW, Grassino A. Diagnosis of diaphragmatic dysfunction. Clin Chest Med 1987;8:91–103.[Medline]
- Booth FW. Time course of muscular atrophy during immobilization of hindlimbs in rats. J Appl Physiol 1977;43:656–661.[Abstract/Free Full Text]
- Ueki J, De Bruin PF, Pride NB. In vivo assessment of diaphragm contraction by ultrasound in normal subjects. Thorax 1995;50:1157–1161.[Abstract]
- Williamson BR, Gouse JC, Rohrer DG, Teates CD. Variation in the thickness of the diaphragmatic crura with respiration. Radiology 1987;163:683–684.[Abstract/Free Full Text]
- Dovgan DJ, Lenchik L, Kaye AD. Computed tomographic evaluation of maximal diaphragmatic crural thickness. Conn Med 1994;58:203–206.[Medline]
- Comtois A, Gorczyca W, Grassino A. Anatomy of diaphragmatic circulation. J Appl Physiol 1987;62:238–244.[Abstract/Free Full Text]
- Fraser RS, Müller NL, Colman N, Paré PD, eds. The diaphragm. In: Fraser and Paré's diagnosis of diseases of the chest. 4th ed. Philadelphia, Pa: Saunders, 1999; 2987–3010.
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ABSTRACT
INTRODUCTION
