Roles of silkworm endoplasmic reticulum chaperones in the secretion of recombinant proteins expressed by baculovirus system.

Baculovirus expression vector system (BEVS) is widely used for production of recombinant eukaryotic proteins in insect larvae or cultured cells. BEVS has advantages over bacterial expression system in producing post-translationally modified secreted proteins. However, for some unknown reason, it is very difficult for insects to secrete sufficiently for certain proteins of interest. To understand the reasons why insect cells fail to secrete some kinds of recombinant proteins, we here employed three mammalian proteins as targets, EPO, HGF, and Wnt3A, with different secretion levels in BEVS and investigated their mRNA transcriptions from the viral genome, subcellular localizations, and interactions with silkworm ER chaperones. Moreover, we observed that no significantly influence on the secretion amounts of all three proteins when depleting or overexpressing most endogenous ER chaperone genes in cultured silkworm cells. However, among all detected ER chaperones, the depletion of BiP severely decreased the recombinant protein secretion in BEVS, indicating the possible central role of Bip in silkworm secretion pathway.

Radiation dose to rectum in high-dose-rate brachytherapy with a single implant and two fractions for prostate cancer, and its prediction by prostate volume.

We aimed to clarify the differences between the estimated rectal dose (ERD) and the first measured dose (FMD) and second measured dose (SMD) to the rectum during high-dose-rate (HDR) brachytherapy, and to predict FMD from the prostate volume (PV) or the rectal dose-volume parameters (RDVPs). ERD, FMD, and SMD were assessed with a rectal dosimeter during HDR brachytherapy of 18 Gy given in two fractions to 110 patients (48 hormone recipients, 62 hormone-naïve patients) with prostate cancer. The correlations between FMD and PV, and between FMD and RDVP (D 2ml-D 5ml) were investigated. ERD (mean ± SD) was 219 ± 44 cGy, FMD was 255 ± 52 cGy, and SMD was 298 ± 63 cGy, which differed significantly (p < 0.001). The correlation coefficients between ERD and FMD, and between FMD and SMD, were 0.82 and 0.78, respectively. SMD was equivalent to 118 ± 16 % FMD. The measured doses were significantly greater in the hormone recipients than in the hormone-naïve patients (p < 0.001). The increase in FMD correlated with the increases in PV and in RDVPs. The correlation coefficients between PV and FMD in all of the patients, in the hormone recipients, and in the hormone-naïve patients were 0.61, 0.64, and 0.64, respectively, whereas that between RDVPs and FMD was <0.53. In conclusion, the dose to the rectum increased with time and was correlated with the increases in PV and RDVPs. The correlation coefficient between FMD and PV was greater than that between FMD and RDVPs.

Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy.

In single photon emission computed tomography-based three-dimensional radiotherapy (SPECT-B-3DCRT), images of Tc-99m galactosyl human serum albumin (GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation images. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepatocellular carcinoma (HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none experienced fatal radiation-induced liver disease (RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients given doses of ≥ 20 Gy (FLV20Gy). Therefore, FLV20Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20Gy as a qualitative index, we propose a quantitative indicator, F 20Gy, which was calculated as F 20Gy = 100% × (the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).

Comparison of air kerma between C-arm CT and 64-multidetector-row CT using a phantom.

PURPOSE: To compare air kerma after scanning a phantom with C-arm CT and with 64-multidetector row CT (64MDCT). MATERIALS AND METHODS: A phantom was scanned using parameters based on data of ten patients with hepatocellular carcinoma who had C-arm CT during hepatic arteriography and 64MDCT during arterial portography. Radiation monitors were used to measure air kerma ten times at each of five points: the center (A), top (B), left side (C), bottom (D), and right side (E). RESULTS: For C-arm CT vs. 64MDCT, air kerma after scanning was 10.5 ± 0.2 vs. 6.4 ± 0.0 for A, 1.5 ± 0.0 vs. 11.6 ± 0.2 for B, 37.1 ± 0.2 vs. 11.1 ± 0.1 for C, 55.6 ± 1.0 vs. 10.6 ± 0.1 for D, and 40.5 ± 0.5 vs. 11.7 ± 0.1 for E, respectively. Air kerma for A, B, C, D, and E was 1.64, 0.13, 3.34, 5.24, and 3.46 times greater for C-arm CT than for 64MDCT, respectively. CONCLUSION: Using the same scanning parameters as for clinical cases, air kerma values were greater with C-arm CT than with 64MDCT; at the dorsal side of the phantom, they were 5.24 times greater with C-arm CT compared with 64MDCT.

Esophageal gel-shifting technique facilitating eradicative boost or reirradiation to upper mediastinal targets of recurrent nerve lymph node without damaging esophagus.

We developed a new technique using hyaluronic gel injection as a spacer to safely move the esophagus away from the high-dose area during interstitial brachytherapy of a mediastinal target close to the esophagus. We percutaneously injected a high-molecular-weight hyaluronic gel mixed with contrast medium to create a space between the esophagus and the target during interstitial brachytherapy. We applied this technique to two cases of relapsed recurrent nerve lymph node metastasis from esophageal cancer: one refractory tumor after 50 Gy of radiotherapy, and one recurrence after mediastinal radiotherapy of total 64 Gy. We prescribed 20 Gy and 18 Gy in one fraction to each target, with calculated esophageal D2cc (the minimum dose to the most irradiated volume of 2 cc) of 4.0 Gy and 6.8 Gy, respectively. Calculated enhancement factor by gel shifting in equivalent dose was 2.69 and 2.34, respectively. In each patient, accumulated esophageal D1cc (minimum dose to the most irradiated volume of p cc. minimum dose to the most irradiated volume of 1 cc) was 74.4 Gy and 85.6 Gy without shifting, and 59.1 Gy and 37.6 Gy with shifting, respectively. There were no procedure-related complications. Four months after the brachytherapy, each tumor was remarkably diminished. No evidence of recurrences or late complications were observed 8 months and 9 months after the procedure, respectively. The esophageal gel-shifting technique may facilitate eradicative brachytherapy to upper mediastinal targets without damaging the esophagus, and can be used in conjunction with boost irradiation or reirradiation to overcome the problem of salvage failure.

Reirradiation of paraaortic lymph node metastasis by brachytherapy with hyaluronate injection via paravertebral approach: With DVH comparison to IMRT.

UNLABELLED: PURPOSE/INTRODUCTION: To safely irradiate retroperitoneal targets as paraaortic lymph node by separating abdominal at-risk organs from the target during irradiation, we created a percutaneous paravertebral approach of high-dose-rate brachytherapy with hyaluronate gel injection (HGI). We report a case treated with this technique. METHODS AND MATERIALS: We encountered a patient with symptomatic regrowth of paraaortic lymph node metastasis from prostatic cancer. He had previously received 58.4Gy of radiotherapy to the same region 12 months prior. Brachytherapy needles and a HGI needle were deployed via the paravertebral approach under local anesthesia at our outpatient clinic. RESULTS: A single dose of 22.5Gy (equivalent to 60.94Gy in 2Gy per fraction schedule calculated at α/ß=10) was delivered to the target, with preservation of the surrounding small intestine by HGI with D(2cc) (minimum dose to the most irradiated volume of 2mL) of 5.05Gy. Therapeutic ratio was 3.64 times higher for this brachytherapy plan compared with an intensity-modulated radiation therapy plan. At followup at 1 year after brachytherapy, the symptoms had disappeared, tumor size had reduced with no fluorodeoxyglucose accumulation, and prostate-specific antigen level had decreased. CONCLUSION: We consider that high-dose-rate brachytherapy with the HGI procedure offers effective treatment even in this type of reirradiation situation.

Novel eradicative high-dose rate brachytherapy for internal mammary lymph node metastasis from breast cancer.

AIM: To develop a method of delivering an eradicative high radiotherapeutic dose safely preserving the surrounding skin in the treatment of internal mammary lymph node metastasis (IMLNM) of breast cancer. METHODS: We report a 38-year-old female patient with a solo IMLNM showing no response to 60 Gy in 2.5 Gy fractions of external beam radiotherapy. To eradicate this tumor, a boost brachytherapy plan was created after percutaneous insertion of an applicator needle into the IMLNM lesion avoiding the pleura and vessels under ultrasound monitoring. According to the dose distribution, the required thickness of a spacer between the skin and the tumor was determined, and hyaluronic gel was injected up to this thickness under ultrasound monitoring. We evaluated skin doses, target doses and clinical outcome. RESULTS: All procedures were performed easily. Sixteen Gy (34.7 Gy equivalent in 2 Gy fractions calculated by the linear quadratic model at α/ß = 10: EQD(2, α/ß = 10), cumulative total was 101.9 Gy EQD10) to 100% of the target volume was irradiated with cumulative maximum skin dose of 70 Gy EQD(2, α/ß = 3) which was 98.7 Gy EQD(2, α/ß = 3) without spacer. No procedure related- or late complications and no local recurrence at the treated site were observed for three years until expiration. CONCLUSION: We consider that this procedure will provide an eradicative high-dose irradiation to IMLNM of breast cancer, preserving skin from overdose complications.

Eradicative brachytherapy with hyaluronate gel injection into pararectal space in treatment of bulky vaginal stump recurrence of uterine cancer.

The purpose of this study is to develop a procedure for eradicative brachytherapy that can deliver a curative boost dose to bulky (>4 cm) vaginal stump recurrence of uterine cancer without risk of damaging surrounding organs. We separated risk organs (the rectum and sigmoid) from the target during brachytherapy, with a hyaluronate gel injection into the pararectal space via the percutaneous paraperineal approach under local anesthesia. The rectum anchored to the sacrum by native ligament was expected to shift posteriorly. We encountered a patient with bulky stump recurrence of uterine cancer, approximately 8 cm in maximum diameter. She was complaining of abdominal pain and constipation due to bowel encasement. Following 50 Gy of external beam radiotherapy, we applied a single fraction of brachytherapy under gel separation and delivered 14.5 Gy (50.8 GyE: equivalent dose in 2-Gy fraction calculated with linear quadratic model at α/ß = 3) to the target. The gel injection procedure was completed in 30 min without complications. A total irradiation dose of 100.8 GyE was delivered to the target and the cumulative minimum dose to the most irradiated rectosigmoidal volume of 2 cc (cumulative D(2cc)) was calculated as 58.5 GyE with gel injection, and was estimated to be 96 GyE without. Over three years, the local stump tumor has completely disappeared, with no complications. Brachytherapy with a pararectal gel injection can be a safe and effective eradicative option for bulky vaginal stump recurrence.

Evaluation of vascular puncture needles with specific modifications for enhanced ultrasound visibility: In vitro study.

AIM: To determine which modification to a vascular puncture needle results in increased visualization during ultrasound (US)-guided vascular puncture. METHODS: We evaluated US images of a phantom made of degassed gelatin and each of the following four modified versions of a commercially available vascular puncture needle (18 G): re-cut needle, dimple needle, rough-surface needle (rough over the sections of needle located 3-6 mm from the tip), and a needle with four side holes (side holes covered by the sheath). An unmodified commercially available puncture needle was used as a control. Five interventional radiologists evaluated image quality according to the following classification grade: I, invisible; II, poor; III, moderate; IV, good; V, excellent. RESULTS: The highest score for needle visualization was obtained for the needle with four side holes. The re-cut needle scored the same as the control. Multiple comparisons were conducted using overall evaluation scores among the commercially available needle, dimple needle, rough-surface needle (3-6 mm), and the needle with four side holes. A significantly higher score was obtained for the needle with four side holes (P < 0.05/6). CONCLUSION: The needle with four side holes was prominently visualized and gained a significantly higher score (compared with the other needles) in a phantom evaluation.

Differentiation of pancreatic serous cystadenoma from endocrine tumor and intraductal papillary mucinous neoplasm based on washout pattern on multiphase CT.

OBJECTIVE: To evaluate the washout (WO) pattern of serous cystadenomas (SCAs) compared with endocrine tumors (ETs) and intraductal papillary mucinous neoplasm (IPMN). METHODS: Patients with serous cystadenoma (n = 12), ET (n = 29), and IPMN (n = 35) underwent 4-phase computed tomography CT. Tumors were categorized as hyperdense or hypodense. Computed tomographic values measured were unenhanced attenuation (AU), pancreatic attenuation (A12, 12 seconds), portal attenuation (A35), and equilibrium (A158). Computed tomographic parameters calculated were wash-in (WI) = A12 - AU; WO = A12 - A35; and washout ratio (WOR) = WO/WI × 100/22. RESULTS: Hyperdense SCAs had significantly higher WOR than did hyperdense ETs (P = 0.001). Among the 3 hypodense tumors, SCAs had the significantly highest WOR (P < 0.05/3). Relative to the pancreas, the WOR of SCAs were equivalent, whereas the WOR of ETs and IPMNs were significantly lower. CONCLUSIONS: Hyperdense SCAs had significantly higher WOR than did hyperdense ETs, and hypodense SCAs had the significantly highest WOR among the three.

Prospective evaluation of transcatheter arterial chemoembolization (TACE) with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil) compared with TACE with epirubicin for treatment of hepatocellular carcinoma.

PURPOSE: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. RESULTS: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). CONCLUSION: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.

Radiotherapy for mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus: a case report with a diagnostic and therapeutic discussion.

Mucosa-associated lymphoid tissue (MALT) lymphoma is increasing common in various sites; however, MALT lymphoma in the esophagus is still rare, so its diagnostic features have not yet been well recognized and optimal treatment has not been properly discussed. Though radiotherapy is widely preferred for gastric and orbital MALT lymphoma, surgery has been the most frequently reported treatment for esophageal MALT lymphoma. This raises the question: why not radiotherapy for esophageal MALT lymphoma instead of surgery? The only reported case of definitive radiotherapy for esophageal MALT lymphoma lacks follow-up data. Three years ago (2007), we treated a 59-year-old male patient with a large esophageal submucosal tumor, diagnosed as MALT lymphoma, with 36 Gy of solo external beam radiotherapy. The tumor was 15 cm in craniocaudal length, homogeneously weakly contrast-enhanced on X-ray computed tomography (CT), homogeneously hypoechoic and clearly demarcated from the surrounding adventitia, and had a concave pattern between the folds. During and after radiotherapy, no treatment-related complications occurred except for transient Grade 2 leukocytopenia. The tumor showed remarkable reduction and histological negativity in the next month. Over the follow-up period, no recurrence was observed in semiannual PET/CT/MRI studies. Taking the current observation with the well known effectiveness of radiotherapy for MALT lymphoma in various other sites, we recommend considering radiotherapy as a reasonable less-invasive treatment for this rare entity.

Reirradiation of prostate cancer with rectum preservation: eradicative high-dose-rate brachytherapy with natural type hyaluronate injection.

INTRODUCTION: Reirradiation of locally recurrent prostate cancer after radiotherapy is limited because of its toxicity to the rectum that is closely adjacent to the prostate. To solve geometric anatomic constraints, including rectal size and distance from the prostate, we developed a technique that modifies the geometry by noninvasive direct intervention. METHODS AND MATERIALS: In a patient with local recurrence of prostate cancer at 18 months after initial radiotherapy of 61.8 GyE(LQ2,3) (gray equivalent in 2 Gy/fraction at α/ß=3 calculated with linear quadratic [LQ] model) to the prostate, we prescribed 16 Gy (60.8 GyE(LQ2,3) or 78.2 GyE(LQ2,1.6)) of reirradiation by high-dose-rate brachytherapy, using a bolus injection of native-type hyaluronate to create and maintain a distance between the prostate and the rectum and decrease rectal size during treatment. RESULTS: The procedure was achieved in 10min, without complications. Rectal D(2cc) of the reirradiation was 5.58 Gy (9.58 GyE(LQ2,3)). Compared with the initial radiation, the gel injection resulted in an improved therapeutic ratio. The patient was regularly followed up at our clinic; at over 3.5 years after reirradiation, there was no evidence of recurrence or radiation-related toxicities greater than Grade 2, maintaining a nadir prostate-specific antigen level of 0.03 ng/mL without hormonal therapy. CONCLUSION: We consider that this technique is useful for achieving safe and curative reirradiation of prostate cancer.

Brachytherapy reirradiation with hyaluronate gel injection of paraaortic lymphnode metastasis of pancreatic cancer: paravertebral approach--a technical report with a case.

Paraaortic lymph nodal (PALN) recurrence is not a rare scenario of abdominal malignancies including pancreas cancer, even after radiotherapy. The role and indication of reirradiation is limited because it is often associated with significant late toxicity in the surrounding normal organs. We developed a new approach and technique of brachytherapy to overcome this difficult situation, with a paravertebral approach and hyaluronate gel injection (HGI). We encountered a patient with pancreatic cancer who developed PALN metastasis as in-field recurrence, 6 months after resection of pancreatic cancer with 50 Gy of preoperative radiotherapy. The applicator brachytherapy needles and gel injection needles were advanced by percutaneous paravertebral approach under local anesthesia, and by injection of a hyaluronate gel to separate the surrounding small intestines and the target. A single fraction of 18 Gy was delivered to the tumor (75.6 Gy equivalent in conventional schedule calculated with LQ model at α/ß = 3) and total estimated D2cc (the minimum dose to the most irradiated volume of 2 cc, calculated at α/ß = 2) in the small intestines was 61.6 GyE with HGI and 80.6 GyE without. No complications have been observed for six months. Three months later, FDG accumulation had disappeared, the tumor size was reduced, and serum CA-19-9 value decreased from 5150 U/mL to 36.6 U/mL (normal range < 37.5). Conclusively, the brachytherapy with the HGI procedure by paravertebral approach was thought safe and effective in reirradiation of PALN recurrence.

Role of external beam radiotherapy for arteriovenous malformation of the pancreas.

Pancreatic arteriovenous malformation (PAVM) is rare and is mainly reported from Asian countries. We incidentally encountered an asymptomatic, early-stage PAVM in a patient who presented with portal venous distention, Child B liver cirrhosis, and hepatoma. The PAVM had multiple feeding arteries and drainage into the portal vein and varices. Because surgery was not indicated, after considering the risks and bene-fits the patient chose treatment with 40 Gy of conformal radiotherapy for 4 weeks. Computed tomography performed 6 months later revealed reduction in the size of the PAVM. Treatment had lasting effects for 18 months without significant toxicity. As observed in many reports of radiotherapy for various AVMs, the radiotherapy may stall self-augmenting growth of the AVM. Conventional fractionated radiotherapy of 40 Gy may be a useful choice for early-stage PAVM.

Effect of interval between transcatheter hepatic arterial embolization and radiofrequency ablation on ablated lesion size in a swine model.

PURPOSE: The aim of the study was to clarify the effect of the interval between transcatheter hepatic arterial embolization (TAE) with Lipiodol plus gelatin sponge particles and radiofrequency (RF) ablation on the extent of ablation. MATERIALS AND METHODS: Eight healthy swine were divided into four groups: RF ablation (ablation only), RF ablation immediately after TAE (immediate ablation), RF ablation 3 days after TAE (3-day ablation), and RF ablation 6 days after TAE (6-day ablation). Five ablated lesions were created in each swine (10 per group). A 2-cm expandable LeVeen needle electrode was used for RF ablation. Ablated lesions are composed of an outer reddish zone and an inner whitish zone. RESULTS: The average longest length of the major, intermediate, and minor axes and the volume in the immediate ablation, 3-day ablation, and 6-day ablation groups were significant longer and greater (1.52 and 1.52, 1.46 and 1.50, and 1.37 and 1.35 times greater in the red zone and the whitish area, respectively) than those in the ablation-only group (P < 0.05/3). Accumulation of Lipiodol was still noted in the hepatic sinusoids in the 3-day and 6-day ablation groups. CONCLUSION: RF ablation delayed to 6 days following TAE produced larger ablation volumes than did RF ablation alone.

Efficacy and safety of high-dose-rate brachytherapy of single implant with two fractions combined with external beam radiotherapy for hormone-naïve localized prostate cancer.

The purpose of this study was to evaluate the efficacy and safety of high-dose-rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naïve prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c-T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15-18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naïve localized prostate cancer, and has low GU and GI toxicities.

Distribution of functional liver volume in hepatocellular carcinoma patients with portal vein tumor thrombus in the 1st branch and main trunk using single photon emission computed tomography-application to radiation therapy.

PURPOSE: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT) by exploring the relation of FLV in MV to radiation-induced liver disease (RILD). METHODS AND MATERIALS: Clinical target volume (CTV) included main tumor and PVTT, and planning target volume (PTV) included CTV with a 10 mm margin. MV was defined as PTV-CTV. FLV ratio in MV was calculated as FLV in MV/MV × 100 (%). The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child-Pugh grade B) with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV × 100 (%). RESULTS: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001). Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200-300 cm3, three with CTV of 500-600 cm3, and two with CTV of 1100-1200 cm3. The destructive ratio yielded a mean value of 24.2 ± 1.5%. CONCLUSIONS: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD.

Prospective comparison of transcatheter arterial chemoembolization with Lipiodol-epirubicin and Lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma.

PURPOSE: The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint. RESULTS: No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513). CONCLUSION: No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups.

Ischemic effects of transcatheter arterial embolization with N-butyl cyanoacrylate-lipiodol on the colon in a Swine model.

This study was designed to assess the safety of transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate-lipiodol (NBCA-Lp) for the large bowel and to investigate the vital response to NBCA-Lp in a swine model. In nine swine, nine arteries nourishing the colon were embolized with NBCA-Lp (1 ml of NBCA mixed with 4 ml of lipiodol): sigmoid-rectal branch artery in six swine, right colic branch artery in two, and middle colic branch artery in one. The amount of NBCA-Lp was 0.1-0.4 ml. Sacrifice was conducted 3 days after TAE to identify histological infarction. Classification was conducted retrospectively: group A, vasa recta without NBCA-Lp embolization despite TAE; group B, three or fewer vasa recta with NBCA-Lp embolization; and group C, five or more vasa recta with NBCA-Lp embolization. In one swine in group A, no necrotic focus was observed. In group B, three of four swine experienced no ischemic damage. The remaining one swine experienced necrosis of mucosal and submucosal layers in one-fourth of the circumference. In group C, all four swine with marginal artery and five vasa recta or more embolized experienced total necrosis of mucosa, submucosa, and smooth muscle layers of the whole colonic circumference. Significant difference on the extent of ischemic damage was observed between groups B and C (P < 0.05). Microscopically, NBCA-Lp induced acute vasculitis. Embolization of three or fewer vasa recta with NBCA-Lp induced no ischemic damage or limited necrosis, whereas embolization of five or more vasa recta with NBCA-Lp induced extensive necrosis.