Endoscopic submucosal dissection combined with the placement of biodegradable stents for recurrent esophageal cancer after chemoradiotherapy.

We report a case of a patient with esophageal squamous cell carcinoma who presented with obstruction of the esophagus. On endoscopy, a central ulcerating lesion was found spreading to the anterior wall of the middle esophagus. Four courses of chemoradiation therapy successfully produced a complete response for 3 years. A recurrence occurred which consisted of a morphologically flat lesion that occupied the entire circumference of the esophagus. Endoscopic submucosal dissection removed all lesions en bloc. To prevent a post-procedure mucosal defect of the circumference of the esophagus, biodegradable poly-l-lactic acid monofilaments esophageal stents were placed on the same day. One month later, the patient reported a feeling of obstruction. An endoscopic examination revealed food stuck in the stents, this was removed, and balloon dilatation provided good passage which has been maintained for 7 months.

Flat-panel detector computed tomography imaging: observer performance in detecting pulmonary nodules in comparison with conventional chest radiography and multidetector computed tomography.

PURPOSE: The aim of this study was to compare the detectability of lung nodules on images obtained with a flat-panel detector computed tomography (FPD-CT) system and by chest radiographs (CXRs) using receiver-operating characteristic (ROC) analysis. MATERIALS AND METHODS: FPD-CT was conducted with the patients in the sitting position. For the CXR study, the patients stood erect. Our study population consisted of 26 individuals ranging in age from 50 to 83 years. The reference standard was based on the interpretations obtained by consensus of 2 radiologists on multidetector CT images for the presence or absence of nodules. Four other radiologists independently assessed and recorded the absence or presence of lung nodules and their location on FPD-CT and CXR images. ROC analysis was used to evaluate lung nodule detectability by both imaging modalities. RESULTS: Two radiologists identified 34 nodules whose diameter was 5 to 42 mm (mean, 19.3 mm) in 23 of the 26 study participants on the multidetector CT images. Overall, analysis of variance for ROC analysis showed that FPD-CT was significantly better in detecting nodules than CXR (P=0.02). The estimated mean Az value was 0.9818±0.0083 with FPD-CT and 0.7610±0.0908 with CXR. The sensitivity for nodule detection on FPD-CT and CXR images was 79.4% and 33.8%, respectively. CONCLUSION: The detectability of pulmonary nodules was better on images of FPD-CT than on CXRs.

Clinical trial of cisplatin-conjugated gelatin microspheres for patients with hepatocellular carcinoma.

PURPOSE: We report our initial experience with the transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC) using cisplatin-conjugated gelatin microspheres (Cis-GMS). METHODS AND MATERIAL: Nineteen patients with 25 HCC nodules (mean diameter 23.0 mm) were treated by selective TACE using 50- to 100-µm Cis-GMS. Tumor necrosis and postembolization syndrome were assessed during the follow-up. The tumor response was evaluated on contrast-enhanced computed tomography images at 1 and 3 months after TACE using Cis-GMS. RESULTS: All procedures were technically successful in all patients; following the TACE using Cis-GMS, there were no major complications, and postembolization syndrome was minimal. At the 1-month follow-up, the response rate was 12 of the 25 (48%) and 21 of the 25 (84%) HCC nodules based on RECIST 1.1 and EASL criteria, respectively; at the 3-month follow-up, it was 10 of the 25 (40%) and 14 of the 25 (56%) HCC nodules, respectively. CONCLUSION: Our initial experience with using Cis-GMS for TACE suggests that these drugs may represent an optimal treatment option for the treatment of advanced HCC and that the use of gelatin microspheres loaded with chemotherapeutic agents warrants further study.

Cisplatin-conjugated porous gelatin particles: assessment of optimal conditions for binding and release.

This study was designed to evaluate the optimal conditions for binding cisplatin and porous gelatin particles (PGPs) and to establish in vivo drug release pharmacokinetics. PGPs were immersed in cisplatin solutions under different conditions: concentration, immersion time, and temperature. Thereafter, PGPs were washed in distilled water to remove uncombined cisplatin and were then freeze-dried. The platinum concentration (PC) in the PGPs was then measured. For the in vivo release test, 50 mg/kg of the cisplatin-conjugated PGPs was implanted subcutaneously in the abdominal region of two rabbits. PCs in the blood were measured at different time intervals. PCs significantly increased in direct proportion to the concentration and immersion time (p < 0.01). Although PC increased at higher solution temperature, it was not a linear progression. For the in vivo release test, platinum was released from cisplatin-conjugated PGPs after 1 day, and the peak PC was confirmed 2 days after implantation. Platinum in the blood was detected until 7 days after implantation in one rabbit and 15 days after administration in the other rabbit. Platinum binding with PGPs increased with a higher concentration of cisplatin solution at a higher temperature over a longer duration of time. Release of cisplatin from cisplatin-conjugated PGPs was confirmed in vivo.

Ability of chest X-ray to detect faint shadows documented as ground-glass attenuation in images of computed tomography: a comparison between flat-panel detector radiography and film-screen radiography.

PURPOSE: To compare flat-panel detector (FPD) radiography and film-screen (FS) radiography in detectability of faint shadows documented as ground-glass attenuation (GGA) areas in images of computed tomography (CT). MATERIALS AND METHODS: Study population was comprised of 50 patients who underwent FS and another 50 patients who underwent FPD. Standard of reference (SOR) was determined on the basis of area of GGA in all cross-sections of CT, in terms of GGA extent and presence or absence of GGA in each trisected lung fields (GGA distribution). Eight radiologists assessed the GGA extent with the 5-grade scale and the GGA distribution. Inter-observer variances of the GGA extents and distributions, degree of divergences and correspondence in the GGA extent and distributions with SOR, were compared between the FS and FPD by the jackknife method and Fisher's exact test. RESULTS: Inter-observer variance in the GGA extent and distribution were slightly larger in the FS than in the FPD. The GGA extent scale corresponded with SOR in the FS statistically significantly better (p=0.001), as the correct ratio was 0.428 in the FS and 0.310 in the FPD. Divergence in the GGA extent scale with SOR was smaller in the FS, as average kappa pseudo-value of Kendall's rank correlation coefficient was 0.474 in the FS and 0.433 in the FPD. CONCLUSION: These results indicate that some lesions of GGA documented in CT may not be reflected and are difficult to be detected in chest X-ray radiographs with the FPD.

Embolization materials made of gelatin: comparison between Gelpart and gelatin microspheres.

PURPOSE: The object of this study was to assess the level of embolization in the embolized artery and the degradation period of these two embolic agents in the renal arteries using rabbit models. MATERIALS AND METHODS: The renal artery was embolized using 5 mg of gelatin microspheres (GMSs; diameter, 35-100 mum; group 1) or 1 mg of Gelpart (diameter, 1 mm; group 2). For each group, angiographies were performed on two kidneys immediately after the embolic procedure and on days 3, 7, and 14 after embolization. This was followed by histopathological examinations of the kidneys. RESULTS: Follow-up angiograms on each day revealed the persistence of poorly enhanced wedge-shaped areas in the parenchymal phase in all cases. In group 1, four of six cases showed poorly enhanced small areas in the follow-up angiograms. In group 2, all cases showed poorly enhanced large areas. In the histopathological specimens, it was observed that immediately after embolization, the particles reached the interlobular arteries in group 1 and the interlobar arteries in group 2. In all cases in group 1, the particles were histologically identified even on day 14. In one case in group 2 on day 14, the particles were not identified. CONCLUSION: In conclusion, although GMSs and Gelpart were similar in the point of gelatin particles, the level of embolization and the degradation period were different between GMSs and Gelpart.

Basic investigation of vascular interventional radiology (IR) using large rabbits.

The purpose of this study was to determine the usefulness of large rabbits for basic vascular interventional radiology (IR) experiments. We used 5 Akita large rabbits (Akita) and 5 Japanese white rabbits (JW). We conducted measurements of vessel diameters such as the aorta, and the iliac, renal, superior mesenteric, celiac, and proper hepatic arteries, and of the growth rates of VX2 liver tumors. There were significant differences between Akita and JW in the diameters of the thoracic aorta, lower abdominal aorta, and celiac artery. In other blood vessels, no significant differences were found. There was no difference in the growth rates of the VX2 tumors between Akita and JW. The possibility that Akita large rabbits could be utilized for vascular IR was demonstrated.

Evaluation of computer-aided detection of lesions in mammograms obtained with a digital phase-contrast mammography system.

A computer-aided detection (CAD) system was evaluated for its ability to detect microcalcifications and masses on images obtained with a digital phase-contrast mammography (PCM) system, a system characterised by the sharp images provided by phase contrast and by the high resolution of 25-µm-pixel mammograms. Fifty abnormal and 50 normal mammograms were collected from about 3,500 mammograms and printed on film for reading on a light box. Seven qualified radiologists participated in an observer study based on receiver operating characteristic (ROC) analysis. The average of the areas under ROC curve (AUC) values for the ROC analysis with and without CAD were 0.927 and 0.897 respectively (P = 0.015). The AUC values improved from 0.840 to 0.888 for microcalcifications (P = 0.034) and from 0.947 to 0.962 for masses (P = 0.025) respectively. The application of CAD to the PCM system is a promising approach for the detection of breast cancer in its early stages.

CT diagnosis of acute mesenteric ischemia from various causes.

OBJECTIVE: Acute mesenteric ischemia can be caused by various conditions such as arterial occlusion, venous occlusion, strangulating obstruction, and hypoperfusion associated with nonocclusive vascular disease, and the CT findings vary widely depending on the cause and underlying pathophysiology. The aim of this article is to review the CT appearances of acute mesenteric ischemia in various conditions. CONCLUSION: Recognition of characteristic CT appearances and the variations associated with each cause may help in the accurate interpretation of CT in the diagnosis of mesenteric ischemia.

An initial clinical study on the efficacy of cisplatin-releasing gelatin microspheres for metastatic liver tumors.

PURPOSE: To evaluate the antitumor effect and side effects of cisplatin-releasing gelatin microspheres (Cis-GMSs) for metastatic liver tumors. METHODS: Cis-GMSs that degraded over 14 days were employed. The subjects comprised a total of nine cases. Transcatheter hepatic artery embolization (TAE) using Cis-GMSs (Cis-GMSs-TAE) was performed 13 times in total. Six cases, each containing one to five tumors in a single segment to an entire lobe were treated by Cis-GMSs-TAE. In the remaining three cases with six or more metastatic liver tumors, the right and left lobes were treated by Cis-GMSs-TAE at a 2-week interval. RESULTS: There were two complete response (CR), one partial response (PR) and six stable disease (SD) cases. The response rate was 33.3%. The average rate of reduction in tumor diameter was 32%. Disappearance of metastatic liver tumors was observed in only two of the nine cases. As for side effects and complications, post-embolization syndrome was observed in eight cases, but no severe complications such as cholangitis or liver abscess were observed. CONCLUSION: Considering the mild side effects by Cis-GMSs-TAE, it is suggested that Cis-GMSs-TAE should be tried at least once as topical therapy for metastatic liver tumors when the response to systemic chemotherapy and other treatments is not satisfactory.

Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits.

PURPOSE: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. MATERIALS AND METHODS: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. RESULTS: The renal parenchymal platinum concentrations (microg/ml) with 4.51+/-2.25 (day 0), 1.59+/-0.70 (day 1), 0.72+/-0.10 (day 3) and 0.20+/-0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99+/-0.55, 0.08+/-0.03, 0.18+/-0.01 and 0.10+/-0.07, respectively. Relative tumor growth rates resulted in 84.5%+/-26.4 (group I); 241.4%+/-145.1 (II); 331.9%+/-72.2 (III), and 413.6%+/-103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. CONCLUSIONS: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an increased and prolonged anti-cancer effect compared to cisplatin alone or controls. Moreover this proves indirectly the breakdown and release of cisplatin from the GMSs which is of primary importance for drug delivery systems.

Cisplatin-conjugated Gelpart: initial study in vitro.

AIM: In Japan, Gelpart (Nippon Kayaku, Tokyo, Japan) is commercially available as an embolic agent made of gelatin for hepatocellular carcinoma. The object of this study was to develop cisplatin-conjugated Gelpart, confirm its bonding capability and confirm cisplatin-release from it in vitro. METHODS: Gelpart (80 mg) were immersed in 50 mL of the cisplatin solution (0.3 mg/mL) at 38 degrees C for 1 hour to allow conjugation to cisplatin. Half of them were washed with double distilled water and centrifuged seven times to remove the uncombined cisplatin from Gelpart. Five mg of washed Gelpart and 5 mg unwashed Gelpart were freeze-dried and the platinum concentrations in these Gelpart were analyzed. In an in vitro release test, 30 mg of each cisplatin-conjugated Gelpart were placed in 10 mL of phosphate buffered salts (PBS) containing 0.01 wt.% Tween 80 and the system was shaken reciprocally at 72 strokes/min at 38 degrees C. At different time intervals (1, 3, 6, 12 and 24 hours), 5 mL of the supernatant was pipetted out and immediately after that the same volume of PBS was added. The platinum concentration of the solutions sampled was measured and the release rate from cisplatin-conjugated Gelpart was calculated. RESULTS: The platinum concentrations (microg/g) of unwashed Gelpart and washed Gelpart were, respectively, 9563.5 +/- 101.1 and 6396.5 +/- 14.8. The release rates (%) from unwashed Gelpart and from washed Gelpart were, respectively, 43.1, 56.3, 56.5, 58.5, 60.9 and 5.8, 6.7, 8.5, 11.0, 12.0. CONCLUSION: Gelpart had a bonding capability to cisplatin and an ability of sustained release from it. Cisplatin-conjugated Gelpart might become a simple embolic agent with drug delivery systems.

Is the use of fullerene in photodynamic therapy effective for atherosclerosis?

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.

Novel biodegradable stents for benign esophageal strictures following endoscopic submucosal dissection.

The application of metallic stents for benign stenosis is limited due to long-term complications. We report here the results of the implantation of a novel biodegradable poly-L-lactic acid (PLLA) esophageal stent in two patients with benign esophageal stenosis after endoscopic submucosal dissection (ESD). Case 1 was a 64-year-old man who received ESD for an early squamous esophageal cancer in the middle esophagus. The mucosal defect was seven-eighths of the circumference, and the distal margin of the resection scar formed the stenosis. After balloon dilatation, the PLLA esophageal stent was endoscopically placed; for 6 months, he has not experienced any symptoms of re-stenosis. Case 2 consisted of a 62-year-old man who developed an early squamous esophageal cancer in the middle esophagus. The lesion was resected by ESD, and the mucosal defect was seven-eighths of the circumference. The resection scar formed the stenosis, and the PLLA esophageal stent was endoscopically placed. He also has not experienced any symptoms of re-stenosis for 6 months. In conclusion, the PLLA esophageal stent provides a new possibility for the management of benign esophageal strictures after ESD. Due to the biodegradable features of this stent, longer term studies are necessary to investigate the relationship between the expected disappearance of the stent and the patency of the stricture.

Gelatin microspheres: initial clinical experience for the transcatheter arterial embolization.

PURPOSE: The purpose of this study is to evaluate the embolization effects of gelatin microspheres (GMSs) when used as an embolic material for transcatheter arterial embolization (TAE) for several organs. MATERIALS AND METHODS: We prepared GMSs that dissolves in 5 days in extravasuclar tissue. GMSs were used in five cases in total, four cases with multiple liver tumors and one case with a pelvic bone tumor. RESULTS: In all five cases, it was possible to treat the targeted tumors by TAE with GMSs. In the contrast-enhanced CT performed 2-4 weeks later, the embolized tumors did not show an enhancement effect. Passage of GMSs in the microcatheter was excellent. CONCLUSION: GMSs showed sufficient potential to be used as an embolic material.

Usefulness of biodegradable stents constructed of poly-l-lactic acid monofilaments in patients with benign esophageal stenosis.

AIM: To report 13 patients with benign esophageal stenosis treated with the biodegradable stent. METHODS: We developed a Ultraflex-type stent by knitting poly-l-lactic acid monofilaments. RESULTS: Two cases were esophageal stenosis caused by drinking of caustic liquid, 4 cases were due to surgical resection of esophageal cancers, and 7 cases were patients with esophageal cancer who received the preventive placement of biodegradable stents for post-endoscopic mucosal dissection (ESD) stenosis. The preventive placement was performed within 2 to 3 d after ESD. In 10 of the 13 cases, spontaneous migration of the stents occurred between 10 to 21 d after placement. In these cases, the migrated stents were excreted with the feces, and no obstructive complications were experienced. In 3 cases, the stents remained at the proper location on d 21 after placement. No symptoms of re-stenosis were observed within the follow-up period of 7 mo to 2 years. Further treatment with balloon dilatation or replacement of the biodegradable stent was not required. CONCLUSION: Biodegradable stents were useful for the treatment of benign esophageal stenosis, particularly for the prevention of post-ESD stenosis.

Laser-guided computed tomography puncture system: simulation experiments using artificial phantom lesions and preliminary clinical experience.

PURPOSE: To conduct computed tomography (CT)-guided puncture exactly and safely, we newly developed a laser guiding puncture system that can be used in a commercially available CT scanner. MATERIALS AND METHODS: The laser-guided CT puncture system is built on the CT table with an aluminum frame. Preliminary simulation tests were conducted using two models representing the body and nodular lesions, and puncture procedures were carried out for 15 patients using this system. RESULTS: The mean distance and standard deviation from the center in simulation experiments conducted using this puncture system were 2.95 +/- 1.20 mm for operator A and 3.52 +/- 1.12 mm for operator B. There was no statistically significant difference between the operators (P = 0.40) or the angles (P = 0.32). For five lung biopsy patients, the distance from the target point planned before biopsy to the actual last puncture point was 0-8 mm. For 10 percutaneous vertebroplasty (PVP) patients (two performed in Th11, one in Th12, five in L1, two in L2), the plan before the puncture procedure was to pass the needle through the vertebral pedicle in all cases. The distance between the planned target point and the actual last puncture point was 0-5 mm. CONCLUSION: This system has the potential to accomplish the CT-guided puncture procedure safely and accurately.

Pluronic F127: application in arterial embolization.

PURPOSE: Pluronic is a substance that is widely used in medical and pharmaceutical fields. In particular, 20% Pluronic F127 solution is a unique substance that is liquid at less than 15 degrees C and gelatinous at 25 to 60 degrees C. In this study, the authors took advantage of the gelation property of Pluronic F127 at human body temperature to simulate embolization and dissolution of the embolism in the renal artery and the superior mesenteric artery (SMA) using a rabbit model. MATERIALS AND METHODS: Four female Japanese rabbits (weight, 2.5-3 kg each) were used. The renal artery was fitted with a 4-F cobra-type catheter and embolized with a 20% Pluronic F127 solution at a temperature of 20 degrees C. The embolic effect was evaluated by angiography immediately after the initial injection and every 15 minutes for 2.5 hours after embolization. After 24 hours, pathologic changes of the renal parenchyma were also evaluated. The embolic effect for SMA and ischemic changes of the intestine were evaluated in the same manner. RESULTS: Angiographic findings showed that Pluronic F127 caused embolization immediately after injection and dissolved in the renal artery and the SMA after 90 to 120 minutes. The pathologic findings showed no ischemic change in the renal parenchyma. Necrosis was not found in the intestine, but focal hemorrhagic changes were extensively present when the gel had dissolved. This suggested that Pluronic F127 dissolved before severe tissue damage could occur. CONCLUSION: Pluronic F127 can potentially be used as a temporary embolic material.

Newly developed biodegradable stents for benign gastrointestinal tract stenoses: a preliminary clinical trial.

We developed an Ultraflex-type stent by knitting polylactic acid monofilaments. The purpose of this study was to evaluate the stent's clinical usefulness for treating benign stenoses in the gastrointestinal tract. The radial force of the biodegradable stent was compared with those of commercially available metallic stents. The measured radial force of the new biodegradable stent was higher than that of commercially available metallic stents. The biodegradable stents were applied in 2 patients with benign gastrointestinal stenoses. The first patient was a 19-year-old female with esophageal stenosis, due to drinking of caustic potash in an attempt to commit suicide. The second patient was a 75-year-old male who had a stenosis at the anastomotic site after esophageal cancer resection. In both cases, the placement of the stent was performed successfully, and the patients' complaints improved immediately after stent placement. There were no complications during stent placement. The stenosis had not recurred at the six-month follow-up examination. In conclusion, the newly developed biodegradable stents were useful in treating benign stenoses of the alimentary tract.

The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube.

RATIONALE AND OBJECTIVES: The image quality of a newly developed full-field digital phase contrast mammography (PCM) system and of a conventional screen-film (SF) mammography system were compared via images of a phantom and receiver operating characteristic (ROC) analysis of clinical images. METHODS: Magnified (1.75X) PCM images were scanned (sampling rate, 43.75 microm) and then reduced to original-sized, 25-micron pixel images printed on photothermographic film. Along with corresponding SF images, the phantom images were evaluated subjectively, and the clinical images of 38 patients were subjected to ROC analysis of mass and microcalcification. RESULTS: In the image quality of a phantom, the PCM exceeded the SF. In both mass and microcalcification, the ROC analysis Az values of the PCM clinical images surpassed those of the SF images. CONCLUSION: The PCM provides better images than the SF. Clinical trials suggest superior detection of both mass and microcalcification by full-field digital PCM over conventional SF mammography.