Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

A case of complete remission of advanced hepatocellular carcinoma with type III portal vein tumor thrombosis treated using transarterial chemoembolization with microspheres and radiation therapy.

Portal vein tumor thrombosis (PVTT) is an extremely locally advanced form of hepatocellular carcinoma. The natural median survival time of patients with hepatocellular carcinoma with PVTT is 2.7 to 4.0 months. A 63-year-old woman visited our clinic complaining of abdominal distention and appetite loss, which she had had for 3 weeks prior to admission. A contrast-enhanced computed tomography scan showed double hepatocellular carcinomas with Type III PVTT and massive ascites caused by arterio-portal shunts within the PVTT. The ascites could not be treated by concentrated ascites reinfusion therapy or diuretics. Transarterial embolization using microspheres followed by radiation therapy against PVTT and five courses of transarterial chemoembolization using microspheres and cisplatin led to the maintaining of complete remission of both ascites and tumors for over 12 months after treatment. Fluoroglucose accumulation of PVTT showed 11.2 as a maximum standard uptake value on positron emission tomography before treatment. No fluoroglucose accumulation within PVTT was observed for over 12 months following treatment. Transarterial chemoembolization using microspheres followed by radiation therapy against Type III PVTT may result in drastic anti-cancer effects and improvement of both serum albumin and intractable ascites after treatment of arterio-portal shunts within the PVTT causing portal hypertension.

Arteriovenous malformation of the pancreas: a case report.

Arteriovenous malformation (AVM) of the pancreas is uncommon in the gastrointestinal tract. We present a case of AVM of the pancreatic head in a 59-year-old male. He was admitted to a hospital with hematemesis and tarry stool and referred to our hospital in March 2014 on the diagnosis of pancreatic artery pseudoaneurysm. A computed tomography scan showed the presence of irregular dilated and/or stenotic vessels with meandering in the pancreatic head. Magnetic resonance imaging showed strong enhancement of the conglomeration in the pancreatic head. Selective angiography showed the proliferation of a vascular network in the pancreatic head and an early visualization of the portal vein at the arterial phase. The patient qualified for surgery with a preoperative diagnosis of AVM of the pancreatic head. We performed pylorus-preserving pancreaticoduodenectomy. The histological results confirmed the presence of irregular dilated tortuous arteries and veins in the pancreatic head. Surgical treatment may represent definitive management of symptomatic AVM.

Prostate cancer: relationships between postbiopsy hemorrhage and tumor detectability at MR diagnosis.

PURPOSE: To retrospectively evaluate the influence of postbiopsy hemorrhage on the accuracy of tumor detection at T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and diffusion-weighted (DW) MR imaging of prostate cancer, with histologic findings as the reference standard. MATERIALS AND METHODS: The institutional review board approved this study and waived the requirement for informed consent. Forty male patients aged 62-84 years (mean age, 71 years) who had prostate cancer underwent MR imaging of the prostate gland after ultrasonographically (US) guided systematic 12-core-specimen biopsy. The mean time between biopsy and MR imaging was 24 days (range, 6-54 days). T1-weighted, T2-weighted, dynamic contrast-enhanced, and DW imaging examinations were performed at 1.5 T. The prostate was divided, according to the biopsy sites, into eight regions on the MR images. Three reviewers in consensus evaluated each region for hemorrhage and prostate cancer. Statistical evaluations were performed with Mann-Whitney U, Ryan, and Spearman rank correlation tests. RESULTS: Intraglandular hemorrhage was observed in 38 (95%) patients and significantly more often in the peripheral zone (PZ) than in the transition zone (TZ) (P < .001). Degree of hemorrhage did not correlate significantly (P = .536) with time between biopsy and MR imaging. The sensitivity, specificity, and accuracy of combined T2-weighted, dynamic contrast-enhanced, and DW imaging in the diagnosis of prostate cancer were 69%, 85%, and 78%, respectively. Sensitivity and specificity were lower for the TZ than for the PZ. Degree of hemorrhage was significantly lower in regions of positive biopsy findings than in regions of negative biopsy findings (P = .001) and correlated negatively with tumor size (P = .043). CONCLUSION: Interpretation of combined T2-weighted, dynamic contrast-enhanced, and DW MR image findings can yield reasonable diagnostic accuracy in both the PZ (80% [191 of 240 regions]) and the TZ (74% [59 of 80 regions]).

Superselective angiographic embolization for intractable epistaxis.

CONCLUSIONS: Routine embolization of the ipsilateral facial artery (FA) is effective because of the high success rate. The use of different embolic materials for the internal maxillary artery (IMA) and the FA was considered safe because of the absence of major complications. OBJECTIVE: To evaluate outcomes of routine embolization of the FA as well as the IMA ipsilateral to the bleeding site for intractable epistaxis, and outcomes using different embolic materials for the FA and the IMA. PATIENTS AND METHODS: Twenty-two patients with intractable epistaxis who underwent superselective embolization were retrospectively analyzed with a mean follow-up of 7 months. The FA and the IMA ipsilateral to the bleeding site were embolized. Two embolic materials, gelatin sponge and microcoils, were used for the IMA and the FA, respectively. RESULTS: The short-term success rate within the first 7 days was 77.3% (17/22). The long-term success rate was 95.5% (21/22). There were no major complications in 22 cases. Minor complications occurred in 13 cases (59%). These minor complications usually did not last more than a week and most resolved within a day.

[Results of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for unresectable liver metastases from colorectal cancer].

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.

Age-related and zonal anatomical changes of apparent diffusion coefficient values in normal human prostatic tissues.

PURPOSE: To identify age-related changes and differences in the diffusion of water molecules within the prostate, through diffusion-weighted imaging (DWI) of the prostate gland in healthy adult Japanese men. MATERIALS AND METHODS: A total of 114 healthy male volunteers (mean age, 55 years; range, 24-81 years) underwent DWI of the prostate with a single-shot echo-planar imaging (EPI) sequence using b-factors of 0 and 1000 seconds/mm(2). Apparent diffusion coefficient (ADC) values of six locations in the peripheral zone (PZ) and two locations in the central gland (CG) were measured and correlations between region and age were examined. RESULTS: ADC values measured within both PZ and CG regions of the prostate showed a uniform distribution, and no significant differences were found between evaluated regions. However, mean ADC values were 1.64 +/- 0.27 x 10(-3) mm(2)/second for PZ and 1.26 +/- 0.12 x 10(-3) mm(2)/second for CG, representing a significant difference. In addition, significant positive correlations were identified between ADC values for both PZ and CG regions and subject age (r = 0.526, P < 0.0001; r = 0.190, P = 0.0431, respectively). CONCLUSION: ADC values within both PZ and CG regions of the prostate increase with age, and this must be taken into consideration when using DWI in the diagnosis of prostate cancer.

Transradial approach for noncoronary angiography and interventions.

PURPOSE: The purpose of this study was to retrospectively evaluate the feasibility and safety of a transradial approach for non-coronary angiography and interventions. BACKGROUND: Generally, the transradial approach is used for coronary angiography and intervention around the world, and experiences have been widely reported. However, few large studies have examined the transradial approach for vessels other than the coronary or cerebral artery. METHODS: Subjects comprised 329 patients who underwent a total of 400 procedures (285 abdomens, 68 pelvises, and 47 lower limbs) with transradial angiography and interventions between January 1999 and June 2006. Normal Allen test results were confirmed before all procedures. A 130- or 150-cm long 4F catheter modified to our own design was used for angiography and interventions such as transarterial embolization or transarterial chemotherapy. RESULTS: Radial artery access was unachievable in 19 of the 400 procedures (4.8%). The radial artery was injured during 1 procedure (0.2%). In the remaining 380 procedures, sufficient angiography was obtained to grasp the condition of indispensable vessels for diagnosis and interventions scheduled in advance succeeded. Total transradial technical success rate in the series was 95%. Frequency of complications such as radial injury or radial spasm was 1.8%. No cases of local hematoma, hand ischemia, or cerebral infarction were encountered. CONCLUSION: The transradial approach was useful for non-coronary angiography and interventions and offers the advantages of low risk and reduced stress on patients.

Evaluation of tris-acryl gelatin microsphere embolization with monochromatic X Rays: comparison with polyvinyl alcohol particles.

PURPOSE: Imaging of blood vessels 30 mum or smaller can be achieved with use of monochromatic x rays. The purpose of the present investigation was to use this method to evaluate the in vivo primary embolic effect of tris-acryl gelatin microspheres and polyvinyl alcohol (PVA) particles in small blood vessels, and specifically to assess the distribution of these particles and the resulting changes in circulation. MATERIALS AND METHODS: Twelve rabbits were divided into four groups: group 1 (PVA particles, 90-180 mum; n = 3), group 2 (tris-acryl gelatin microspheres, 40-120 mum; n = 3), group 3 (PVA, 300-500 mum; n = 3), and group 4 (tris-acryl gelatin microspheres, 300-500 mum; n = 3). After microangiography with monochromatic x rays, embolization was performed in normal auricular blood vessels, and immediately thereafter, postembolization microangiography was performed. Images acquired before and after embolization with the four embolic agents were compared, and the diameters of embolized blood vessels were measured. The mean embolized vascular diameter and its ratio to the midrange particle size of the embolic agent were calculated. RESULTS: Tris-acryl gelatin microspheres did not aggregate and tended to lodge in vessels close in size to the individual particle size, whereas PVA particles aggregated in vessels larger than the individual particle size. For tris-acryl gelatin microspheres, no blood flow was noted peripheral to the embolized region, whereas for PVA particles, blood flow was noted in regions peripheral to the embolized region. CONCLUSIONS: Monochromatic x rays allow direct visualization of in vivo embolic properties. This technique holds promise for comparative studies of embolic agents.

Three-dimensional trabecular bone architecture of the lumbar spine in bone metastasis from prostate cancer: comparison with degenerative sclerosis.

OBJECTIVE: Prostate cancer frequently metastasizes to bone, inducing osteosclerotic lesions. The objective of this study was to clarify the three-dimensional (3D) trabecular bone microstructure in bone metastasis from prostate cancer by comparison with normal and degenerative sclerotic bone lesions, using microcomputed tomography (micro-CT). DESIGN AND MATERIALS: A total of 32 cancellous bone samples were excised from the lumbar spine of six autopsy patients: 15 metastatic samples (one patient), eight degenerative sclerotic samples (four patients) and the rest from normal sites (three patients). The samples were serially scanned cross-sectionally by micro-CT with a pixel size of 23.20 microm, slice thickness of 18.56 microm, and image matrix of 512 x 512. Each image data set consisted of 250 consecutive slices. The volumes of interest (96 x 96 x 120 voxels) were defined in the original image sets and 3D indices of the trabecular microstructure were determined. RESULTS: The trabecular thickness (Tb.Th) in degenerative sclerotic lesions was significantly higher than that in normal sites, whereas no significant difference was observed in trabecular number (Tb.N). By contrast, in metastatic lesions, the Tb.N was significantly higher with increased bone volume fraction (BV/TV) than in normal sites, and no significant difference was found in Tb.Th. The characteristics of the trabecular surface in the metastatic samples showed concave structural elements with an increase in BV/TV, indicating osteolysis of the trabecular bone. In 3D reconstructed images, increased trabecular bone with an irregular surface was observed in samples from metastatic sites, which were uniformly sclerotic on soft X-ray radiographs. CONCLUSION: These results support, through 3D morphological features, the strong bone resorption effect in bone metastasis from prostate cancer.

Evaluation of serum KL-6 as a predictive marker of radiation pneumonitis in patients with breast-conservation therapy.

BACKGROUND: Although radiation pneumonitis in radiotherapy following breast-conservation surgery is rare, it may lead to severe pneumonitis as well as to other types of pulmonary dysfunction. This study examined the usefulness of the serum KL-6 level as a new marker for the early detection of radiation pneumonitis. METHODS: Twenty-nine consenting patients served as subjects (age range, 32-78 years; mean age, 51 years) between 2001 and 2002. A total tangential irradiation dose of 50 Gy/25 fractions (fr) was administered for 5 weeks, using a 4-MV X-ray, and an additional 10 Gy/5 fr for 1 week of 6-MeV electron-beam irradiation was performed for patients with pathological tumor cell findings in the excised tumor margins. Levels of serum KL-6 were measured before and after radiotherapy. RESULTS: Four patients developed radiation pneumonitis, all of whom had elevated post-therapy KL-6 levels. Patients with lower or unchanged KL-6 levels did not develop radiation pneumonitis. There was a significant difference in serum KL-6 levels between patients with and without radiation pneumonitis (P = 0.0421). KL-6 levels remained below the threshold value of 465 U/ml in all patients. CONCLUSION: For the early detection of radiation pneumonitis following breast-conservation surgery, and to assess the efficacy of therapy, the monitoring and measuring of changes in KL-6 levels before and after radiotherapy is more important than comparing KL-6 levels against the threshold value. Measuring KL-6 serum levels is also useful in assessing the efficacy of therapy for radiation pneumonitis.

Iatrogenic venous air embolism caused by CT injector--from a risk management point of view.

An iatrogenic venous air embolism caused by computed tomography (CT) injector occurred in a 74-year-old man undergoing abdominal-pelvic CT for evaluation of an abdominal aortic aneurysm (AAA). During the initial inspection scan of the thoracic part, a large amount of air was detected in the right ventricle, but no contrast medium was noted in the aorta. Surface oxygen was given immediately, and the patient was placed in the left lateral decubitus position on the CT bed. During that time he had no symptoms except coughing. CT revealed no air in the brain or pulmonary vein, and he was returned to his room 55 minutes after the incident. There were no complications during a six-month follow-up period. The importance of daily risk management and immediate proper after care to prevent such accidents was reconfirmed.

Observation of microvasculatures in athymic nude rat transplanted tumor using synchrotron radiation microangiography system.

RATIONALE AND OBJECTIVES: The diagnostic potential of tumor microvasculatures with the monochromatic synchrotron radiation microangiography (MSRA) system was examined in an experimental model using athymic nude rats. MATERIALS AND METHODS: In the lower abdominal wall in athymic nude rats (male, 120-150 g, 6 weeks old), 1 x 10(7) cells of N-nitrosomethylurea-induced rat mammary adenocarcinoma was transplanted to prepare a lower abdominal wall tumor transplanted model. A microcatheter was inserted in the abdominal aorta in a rat under anesthesia, and microangiographic images of the normal inferior epigastric artery and vein were obtained using an MSRA system. Changes in the tumor microvasculatures were observed using an MSRA system on the day 7 (n = 3), day 14 (n = 3), day 21 (n = 3), and day 28 (n = 3) after transplant. In addition, we measured the microvessel density (MVD) with a computer using the binarization method. These results were compared among the histologic MVDs. RESULTS: The microvasculatures of tumors measuring 20-30 microm were observable by the MSRA system in the transplanted tumor model using the inferior epigastric artery and vein as the feeding vessels. The tumor microvasculatures were observed for 7-28 days after transplantation. The tumor MVD obtained by the binarization method increased as the tumor volume increased. When histologic MVD was compared with the fixed quantitative results of angiographic MVD, a significant correlation (r = 0.933, P <.01) was observed. CONCLUSION: These preliminary investigations indicate that MSRA proved to be suitable for quantification and appears to be a simple method for clearly imaging tumor microvasculatures.

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma by whole-body MRI: comparison with bone and 67Ga scintigraphies.

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from (67)Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and (67)Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkin's lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by (67)Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than (67)Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by (67)Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkin's lymphoma.

T2-weighted MR imaging of prostate cancer: multishot echo-planar imaging vs fast spin-echo imaging.

The aim of the present study was to assess the performance of pre-biopsy T2-weighted MR imaging using multishot echo-planar imaging (EPI) sequence for visualization of prostate cancer and to compare image quality with that of fast spin-echo (FSE) sequence. Thirty-nine patients with suspected prostate cancer and one healthy male volunteer were examined on a 1.5-T MR scanner equipped with a pelvic phased-array coil. Axial MR images were obtained using multishot EPI sequence with a multishot number of 16 and FSE sequence without fat suppression. Paired EPI and FSE images were independently evaluated by three radiologists. Furthermore, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between EPI and FSE images of 12 pathologically proven lesions of prostate cancer. Delineation of the periprostatic venous plexus, prostate zonal anatomy, and seminal vesicle on EPI was graded to be superior/inferior to FSE in 15.8/0, 14.6/0, and 21.5/4.3% of cases, respectively. On the other hand, delineation of the neurovascular bundle was superior/inferior to FSE in 2.6/13.2% of cases. The SNR and CNR of prostate cancer on EPI were significantly higher than those on FSE (7.99 +/- 2.51 vs 3.36 +/- 0.58, p<0.0001, and 5.51 +/- 2.02 vs 2.21 +/- 0.79, p<0.0001, respectively). In conclusion, multishot EPI has higher quality of contrast resolution for imaging of prostate cancer compared with FSE and would have the potential usefulness in the detection of prostate cancer, although these results obtained with a phased-array coil cannot be extrapolated to examinations performed with an endorectal coil.

[A case of thymic carcinoma responded to intra-arterial chemotherapy combined with radiation therapy].

A 70-year-old male complained of pain in the left neck. A tumor of about 8 cm in diameter was detected by contrast CT in the region extending from the anterior to upper mediastinum. For definitive diagnosis, biopsy was performed under CT guidance, and the patient was diagnosed as having anaplastic carcinoma in the thymus (T4, N1, M0, stage IVb). Since surgical treatment was judged to be impossible because of infiltration into large blood vessels, the patient underwent chemotherapy by intra-arterial injection (CDDP, ADM) and radiotherapy (45 Gy), and obtained a CR. Metastasis to the spleen was detected during the follow-up period, but a CR was obtained by chemotherapy by intra-arterial injection (CDDP) and systemic chemotherapy (TXL). Generally, the prognosis for carcinoma in the thymus is poor, and the prognosis for anaplastic carcinoma in the thymus is considered especially poor. However, chemotherapy by intra-arterial injection of carcinostatics such as CDDP can be applied to patients in whom surgical treatment is impossible.

A long-term survivor of leiomyosarcoma around the right side of the base of the skull: effective radiotherapy combined with intra-arterial chemotherapy.

We report a rare case of a leiomyosarcoma that developed around the right side of the base of the skull in a 51-year-old woman. The patient consulted our hospital complaining of pain in the right side of her neck and upper right arm in August 1994. A leiomyosarcoma, originating around the right side of the neck and base of the skull was diagnosed. Initially, surgery was planned, but invasion into the spinal canal was discovered. Curative resection of the leiomyosarcoma around the right side of the base of the skull was not possible. Therefore, external beam radiotherapy (EBRT) combined with intra-arterial chemotherapy and hyperthermia was employed. After the treatment, the tumor decreased in size to 45% of its initial volume, and, simultaneously, her symptoms completely disappeared. The patient initially remained clinically free of the disease, but showed reaggravations at the primary tumor site 3 years and 3 months, and 4 years and 11 months, after the first treatment. The reaggravations were treated with EBRT combined with intra-arterial chemotherapy. As a result, she survived for 5 years and 7 months after the first treatment.

[A case of advanced hypopharyngeal carcinoma successfully treated with superselective intra-arterial infusion of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for advanced/recurrent head and neck cancer. A 67-year-old male with advanced hypopharyngeal cancer (T3N2bM1: Stage IV) underwent two courses of superselective intra-arterial infusion of docetaxel and intravenous administration of CDDP and 5-FU. Using a coaxial technique, a microcatheter was placed in the feeding artery. Using imaging techniques docetaxel (60 mg/body and 30 mg/body) was infused into the vessels. During chemotherapy the patient received concomitant radiotherapy (50 Gy). MRI after chemoradiation showed a complete response for the primary tumor and a partial response for the neck metastasis. Grade 4 leukopenia and neutropenia and grade 3 pharyngitis/esophagitis were observed during chemoradiotherapy, but these adverse effects abated immediately and were not critical. We conclude that this superselective intra-arterial infusion of docetaxel will be useful and safe for head and neck cancer.