SU-E-J-117: Computer-Assisted Verification of Accumulated Dose Distribution during the Treatment Time Based on Estimation of Four-Dimensional Dose Distribution Using an Electronic Portal Imaging Device.

PURPOSE: The accumulated dose distributions during the course of radiation treatment are substantially important for verifying whether treatment dose distributions are produced according to planned dose distributions. The purpose of this study was to develop a computer-assisted verification method of accumulated dose distribution during the irradiation of a tumor based on estimation of four-dimensional (4D) dose distribution using an electronic portal imaging device (EPID). METHODS: The 4D 'treatment' computed tomography (CT) images during the irradiation were estimated based on affine transformations including respiratory motions, which were derived by registration between a planning portal dose image and treatment portal dose dynamic image. Planning portal dose images were calculated from planning CT images and an algorithm for calculation of dose spatial distribution. Treatment portal dose images were estimated from EPID dynamic images obtained during a treatment time. The planning portal dose images were registered to the treatment portal dose images to obtain the affine transformation, which could include respiratory motion in a patient body. The CT images at a treatment time were determined by deforming the planning CT images using the affine transformation matrix. 4D dose distributions during a treatment delivery were obtained by applying a dose calculation algorithm to the 4D treatment CT images. Finally, accumulated dose distributions during the course of radiation treatment were verified with planned dose distributions. RESULTS: We applied the proposed method to EPID dynamic images of 2 lung cancer patients, and evaluated the difference in accumulated dose distribution between the plan and treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases was 78.2%. CONCLUSIONS: The proposed method can be used for adaptively modifying the plan based on the dose discrepancy between the plan and treatment. This work was partially supported by Grant-in-Aid for Scientific Research (C) (22611011) and Okawa Foundation for Information and Telecommunications.

SU-E-J-26: Automated Estimation Method of Patient Setup Errors Using Simulated Portal Images for Prostate Cancer Radiotherapy.

PURPOSE: We developed a novel automated estimation method for patient setup errors based on simulated and real portal images for prostate cancer radiotherapy. METHODS: The estimation of patient setup errors in this study was based on a template matching technique with a cross-correlation coefficient and Sobel filter between the real portal image and localized pelvic template of reference image, which were DRR (digitally reconstructed radiography) images and simulated portal images. The simulated portal image was derived by projecting a CT image according to an inverse exponential power law of x-ray attenuation for a water-equivalent path length of each voxel of the CT image on each ray from a source to each pixel on the EPID (electric portal imaging device). A localized pelvic template of each patient in AP (anterior-posterior) or lateral view was automatically extracted from the DRR or simulated portal images by cropping a rectangular region, which was determined by using the mean pelvic template and four anatomical feature points. We applied the proposed method to three prostate cancer cases, and evaluated it using the residual error between the patient setup error obtained by proposed method and the gold standard setup error determined by two radiation oncologists. RESULTS: The average residual errors of the patient setup error for the DRR and simulated portal images were 0.79 and 1.26 mm in the left-right (LR) direction, 3.17 and 2.05 mm in the superior-inferior (SI) direction, 1.69 and 5.82 mm in the anterior-posterior (AP) direction, 3.84 and 6.94 mm in Euclidean distance (ED), respectively. If we used the simulated portal image for LR and SI directions and the DRR image for AP direction, the Euclidean distance was 3.22 mm. CONCLUSIONS: The proposed method has a potential to correctly estimate patient setup errors for prostate cancer radiotherapy.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Favorable quality of life after repeat hepatic resection for recurrent hepatocellular carcinoma.

BACKGROUND/AIMS: The appropriate choice of treatment for recurrent hepatocellular carcinoma after hepatic resection remains controversial. The aim of this study is to clarify prognostic factors and quality of life in patients with tumor recurrence after hepatic resection for hepatocellular carcinoma. METHODOLOGY: We retrospectively analyzed 188 patients with hepatocellular carcinoma who underwent curative hepatic resection between 1988 and 1997. Statistical analysis was performed to identify prognostic factors involved after recurrence. Furthermore, quality of life after treatment for recurrence was compared between patients with repeat hepatic resection or hepatic arterial infusion chemotherapy. RESULTS: In 123 patients with recurrence, unfavorable predictors after recurrence are pTNM Stage III/IV at initial surgery, receiving chemotherapy before initial surgery and presence of extrahepatic recurrence. In contrast, favorable predictors are 3 years or more of disease-free interval and repeat hepatic resection. The incidence of deteriorated performance status in the repeat hepatic resection group was lower than in the hepatic arterial infusion chemotherapy group because of better psychological function in patients undergoing repeat hepatic resection. CONCLUSIONS: Repeat hepatic resection provides a good prognosis and a favorable quality of life in patients with recurrence after hepatic resection for hepatocellular carcinoma.

Risk prediction using histology of noncancerous liver before hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study is to elucidate the feasibility of the risk assessment of hepatic resection by histological evaluation of noncancerous liver in patients with hepatocellular carcinoma. METHODOLOGY: The study involved 78 patients with hepatocellular carcinoma who had undergone a needle biopsy of noncancerous liver before hepatic resection. The histological activity index score which consists of four categories indicating the inflammatory activity and the degree of fibrosis was determined, and its association with complications after hepatic resection was examined. RESULTS: Postoperative complications occurred in 26 of the first 52 patients that underwent hepatic resection. A logistic analysis selected histological activity index score as an independent factor related to postoperative complications (Odds ratio 1.31, P < 0.02). Postoperative complications occurred more frequently in patients with a histological activity index score > or = 6 that had undergone resection of two or more segments (P < 0.05), and also in those with histological activity index score > or = 10 that had undergone segmentectomy or subsegmentectomy (P < 0.05). When the histological activity index score was taken into consideration in deciding operative procedures for a further 20 patients, the incidence of postoperative complications reduced considerably to 10%. CONCLUSIONS: Preoperative histological evaluation of noncancerous liver by a needle biopsy may be helpful in deciding the operative procedure to avoid complications after hepatic resection for hepatocellular carcinoma.

Hepatocyte growth factor promotes liver regeneration and protein synthesis after hepatectomy in cirrhotic rats.

BACKGROUND/AIMS: Hepatocyte growth factor, a potent mitogen for hepatocytes has been reported to be a hepatrophic factor in normal livers. In this study, the effect of exogenous hepatocyte growth factor on liver regeneration in cirrhotic rats was investigated, in vitro and in vivo. METHODOLOGY: Liver cirrhosis was induced by intraperitoneal injections of an emulsion, carbon tetrachloride and olive oil, twice weekly for 10 weeks. In vitro, various amounts of exogenous hepatocyte growth factor; 0, 0.5, 1, 2.5, 5, and 10 ng/mL; were added to the hepatocytes isolated using in situ perfusion method. In vivo, partial hepatectomy (Hx), according to the procedure described by Higgins and Anderson, was performed on cirrhotic rats. Saline solution (control group) or 3 micrograms/kg of exogenous hepatocyte growth factor (HGF group) was then injected through the tail vein at intervals 12 hours after Hx. RESULTS: In vitro, DNA synthesis in hepatocytes obtained from cirrhotic livers increased following exogenous hepatocyte growth factor in dose-dependent fashion. In vivo, the labeling index of 5-bromo-2'-deoxyuridine at 24 hours after Hx was markedly increased by exogenous hepatocyte growth factor (control, 10.0 +/- 3.1%; hepatocyte growth factor, 25.8 +/- 9.8%; P < 0.01). Furthermore, serum albumin at 24 and 72 hours and a normotest at 24 hours after Hx, were significantly higher in the HGF group than in the control group. CONCLUSIONS: These results indicate that exogenous hepatocyte growth factor may promote DNA synthesis and protein synthesis during liver regeneration after Hx with cirrhosis.

Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis.

BACKGROUND: The hepatitis activity index (HAI) score describes the histologic status of accompanying chronic hepatitis and was established by pathologists. The aim of this study was twofold: 1) to investigate the correlation between intrahepatic metastatic recurrence (IM) and the HAI score of the noncancerous region of the liver and 2) to estimate the usefulness of postoperative preventive chemotherapy in patients with hepatocellular carcinoma (HCC). METHODS: The study included 158 consecutive patients who underwent curative resection for HCC and had been observed for > 1 year. Based on the HAI scores of the noncancerous region the patients were classified into 3 groups: those with mild hepatitis (n = 33) (i.e., with HAI scores of 0-5), those with moderate hepatitis (n = 77) (with HAI scores of 6-9), and those with severe hepatitis (n = 48) (those with HAI scores of > or = 10). In addition, a prospective randomized trial of postoperative adjuvant chemotherapy was performed for 21 patients with moderate hepatitis. RESULTS: The patients in the moderate hepatitis group were found to be at higher risk for IM recurrence within 2 years after HCC resection compared with those patients in the mild (P = 0.05) and severe (P < 0.01) hepatitis groups. The incidences of more than two tumors and portal vein involvement in patients with moderate hepatitis were much higher than in those patients with mild or severe hepatitis. Multivariate analysis showed that intraoperative bleeding volume, the number of nodules, portal vein involvement, and moderate hepatitis were independent predictive factors for IM recurrence free survival. Ten patients with moderate hepatitis had received postoperative intrahepatic arterial chemotherapy (2-3 courses with a maximum dose of 80 mg of cisplatin and 10 mg of mitomycin C at 1-month intervals) for the last 3 years. Although the number of patients was small, the therapy improved the disease free survival rate significantly compared with 11 patients who received no therapy. CONCLUSIONS: The patients with moderate hepatitis (HAI score of 6-9) had the highest rate of IM recurrence among the three HAI groups. Postoperative hepatic arterial chemotherapy may be useful in improving the rate of disease free survival after surgery among these patients.

Massive hemorrhage after biopsy of an esophageal polyp.

Esophageal vascular malformations are very rare. Herein, we describe a rare polyp formed by an abnormally large vessel that bled profusely after biopsy. Despite endoscopic procedures, the patient continued to bleed and underwent emergency surgery. Histopathological examination revealed an abnormally large blood vessel with a thick wall in the upper part of the lamina propria mucosae and covered by squamous cell epithelium. The elevated lesion, which was endoscopically diagnosed a small polyp, was in fact an abnormally large artery covered by squamous cell epithelium. Massive bleeding after biopsy of an esophageal polyp is apparently so rare that it has not, as yet, been described.

Response of patients with cirrhosis who have undergone partial hepatectomy to treatment aimed at achieving supranormal oxygen delivery and consumption.

BACKGROUND: This study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index > than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170 ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and to assess the relationship between those parameters and outcome. METHODS: Thirty-four consecutive patients underwent elective hepatectomy for hepatocellular carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values in 16 patients (group S) who maintained supranormal values were compared with those in 18 patients (group N) treated to maintain normal hemodynamic values. Patients in group S received volume expansion and then, if necessary, dobutamine (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and oxygen comsumption simultaneously during the first 12 hours. RESULTS: The hemodynamic targets were reached by 56% of patients in group S during the first 12 hours and 31% during the next 12 hours. Postoperative blood lactate levels at 12 and 24 hours were lower in group S than in group N, and total bilirubin concentrations, hepatic venous oxygen saturation, and arterial ketone body ratio, useful markers of postoperative liver function, also showed more favorable changes in group S than in group N. Postoperative morbidity and mortality rates were not significantly different in the two groups, but the incidence of hyperbilirubinemia and liver failure was much lower in group S than in group N. CONCLUSIONS: These results suggest that fluid therapy aimed at achieving a supranormal pattern by 12 hours after hepatectomy improved the systemic oxygen demand-supply dynamics and hepatic hemodynamics, decreasing the incidence of postoperative hyperbilirubinemia and liver failure in patients with liver cirrhosis.

Postoperative management following massive hepatectomy in a patient with Dubin-Johnson syndrome: report of a case.

We report herein the case of a 46-year-old man with Dubin-Johnson syndrome (DJS) who was referred to our hospital to undergo a right hepatic lobectomy for hepatocellular carcinoma. His complicated postoperative conjugated hyperbilirubinemia was successfully treated by hemopurification based on the increased level of serum hepatocyte growth factor (HGF). It is considered that hemopurification based on the early postoperative HGF levels has beneficial effects for patients with DJS; however, the specific role of hemopurification in the conjugated hyperbilirubinemia that develops postoperatively in these patients has not been determined.

Hepatic hemodynamics in a patient with nodular regenerative hyperplasia.

Nodular regenerative hyperplasia of the liver is an uncommon condition. Approximately 50% of these patients develop portal hypertension. Few previous reports document the site of increased resistance to blood flow within the liver in this disorder. We measured Doppler waveform patterns of the right hepatic vein by pulsed Doppler ultrasonography and portal, wedged hepatic, and free hepatic venous pressure by intravenous catheter before and after splenectomy in a 47-yr-old woman with nodular regenerative hyperplasia who presented with portal hypertension and pancytopenia. Nodular regenerative hyperplasia was histologically confirmed. Pre- and postoperative measures indicated a marked difference between wedged hepatic venous pressure and free hepatic venous pressure, whereas there was little difference between portal venous pressure and wedged hepatic venous pressure. Doppler waveform patterns of the right hepatic vein showed an unclear pulsatile flow pattern with a decreasing reversed phase. The above data suggest that portal hypertension in nodular regenerative hyperplasia is primarily sinusoidal, similar to that seen with cirrhosis.

Expression of HGF and TGF-beta 1 mRNA after partial hepatectomy in rats with liver cirrhosis.

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1.