Concurrent hyperthermia and re-irradiation for recurrent high-grade gliomas.

Salvage therapy for recurrent high grade gliomas (HGG) includes surgery, radiotherapy and chemotherapy, however, standard treatment does not exist. We evaluated the tolerability and efficacy of re-irradiation (re-RT) with hyperthermia (HT) for patients with recurrent HGG. From September 2010 to July 2015, 20 patients with recurrent HGG were treated with re-RT and HT. The radiotherapy dose of 30 Gray (Gy) was delivered with 2 Gy per fraction daily, and HT was performed twice weekly. Primary endpoints were treatment compliance and toxicity. Second endpoints were overall survival (OS) and progression free survival (PFS). The median interval between initial RT and re-RT was 11 months. During re-RT with HT, there were no significant acute morbidities over grade 3. Median overall survival (OS) from re-irradiation was 8.4 months and the 6 and 12 months survival rate were 67% and 30%, respectively. The median progression free survival (PFS) from re-irradiation was 4.1 month. Our findings suggested that concurrent re-RT with HT was a safe and well-tolerated. In addition, the combination re-RT and HT could be a valuable salvage treatment option for selected recurrent HGG patients with poor performance status.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma.

PURPOSE: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). METHODS/PATIENTS: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). RESULTS: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. CONCLUSIONS: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer -- single institution retrospective analysis.

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.

Concurrent chemoradiotherapy in patients with nasopharyngeal cancer: prognostic significance of low expression of bax.

A randomized trial has demonstrated that concurrent chemoradiotherapy (CRT) is superior to radiotherapy (RT) alone in locally advanced nasopharyngeal cancer (NPC). Our study comprise 35 patients with locally advanced NPC (stage I: 1, II: 12, III: 7, IV: 15) with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m(2)/day and cisplatin 20 mg/m(2)/day, days 1- 4) followed by concurrent CRT starting on day 22. Concurrent CRT consisted of RT (70 Gy/35 fractions for 7 weeks) with cisplatin 20 mg/m(2)/day for 4 days on weeks 1, 4, 7 of RT. Complete response (CR) was achieved in 33 patients (94%). Four-year progression-free survival (PFS) and overall survival (OS) of all patients were 57% and 65%, respectively. In analysis of prognostic factors, low expression of bax was the most significant independent predictor of poor prognosis in both PFS (p=0.002) and OS (p=0.008). In conclusion, the outcome of patients treated with this combined therapeutical modality appears to be comparable with that of Intergroup 0099 trial with high CR rate. Low expression of bax was significantly associated with poor PFS and OS.

Inhibition of mTOR complex 2 induces GSK3/FBXW7-dependent degradation of sterol regulatory element-binding protein 1 (SREBP1) and suppresses lipogenesis in cancer cells.

Cancer cells feature increased de novo lipogenesis. Sterol regulatory element-binding protein 1 (SREBP1), when presented in its mature form (mSREBP1), enhances lipogenesis by increasing transcription of several of its target genes. Mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, are master regulators of cellular survival, growth and metabolism. A role for mTORC1 in the regulation of SREBP1 activity has been suggested; however, the connection between mTORC2 and SREBP1 has not been clearly established and hence is the focus of this study. mTOR kinase inhibitors (for example, INK128), which inhibit both mTORC1 and mTORC2, decreased mSREBP1 levels in various cancer cell lines. Knockdown of rictor, but not raptor, also decreased mSREBP1. Consistently, reduced mSREBP1 levels were detected in cells deficient in rictor or Sin1 compared with parent or rictor-deficient cells with re-expression of ectopic rictor. Hence it is mTORC2 inhibition that causes mSREBP1 reduction. As a result, expression of the mSREBP1 target genes acetyl-CoA carboxylase and fatty-acid synthase was suppressed, along with suppressed lipogenesis in cells exposed to INK128. Moreover, mSREBP1 stability was reduced in cells treated with INK128 or rictor knockdown. Inhibition of proteasome, GSK3 or the E3 ubiquitin ligase, FBXW7, prevented mSREBP1 reduction induced by mTORC2 inhibition. Thus mTORC2 inhibition clearly facilitates GSK3-dependent, FBXW7-mediated mSREBP1 degradation, leading to mSREBP1 reduction. Accordingly, we conclude that mTORC2 positively regulates mSREBP1 stability and lipogenesis. Our findings reveal a novel biological function of mTORC2 in the regulation of lipogenesis and warrant further study in this direction.

Inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs response of cancer cells to DR5-mediated apoptosis and T cell-induced killing.

Inhibition of B-Raf/MEK/ERK signaling is an effective therapeutic strategy against certain types of cancers such as melanoma and thyroid cancer. While demonstrated to be effective anticancer agents, B-Raf or MEK inhibitors have also been associated with early tumor progression and development of secondary neoplasms. The ligation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with its receptor, death receptor 5 (DR5), leading to induction of apoptosis, offers a promising anticancer strategy. Importantly, this is also a natural immunosurveillance mechanism against cancer development. We previously demonstrated that activated B-Raf/MEK/ERK signaling positively regulates DR5 expression. Hence, our current work sought to address whether B-Raf/MEK/ERK inhibition and the consequent suppression of DR5 expression impede cancer cell response to DR5 activation-induced apoptosis and activated immune cell-induced killing. We found that both B-Raf (for example, PLX4032) and MEK inhibitors (for example, AZD6244 and PD0325901) effectively inhibited ERK1/2 phosphorylation and reduced DR5 levels in both human thyroid cancer and melanoma cells. Similar to the observed effect of genetic knockdown of the B-Raf gene, pre-treatment of cancer cell lines with either B-Raf or MEK inhibitors attenuated or abolished cellular apoptotic response induced by TRAIL or the DR5 agonistic antibody AMG655 or cell killing by activated T cells. Our findings clearly show that inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs DR5 activation-induced apoptosis and T cell-mediated killing of cancer cells. These findings suggest a potential negative impact of B-Raf or MEK inhibition on TRAIL- or DR5-mediated anticancer therapy and on TRAIL/DR5-mediated immune-clearance of cancer cells.

Abdominal Aortic Calcification in Living Kidney Donors.

OBJECTIVE: This study assesses the association between abdominal aortic calcification (AAC) and renal function of living kidney donors and evaluate AAC as a surrogate marker for nephrosclerosis. METHODS: Between January 2010 and March 2013, 287 donors who underwent living donor nephrectomy were enrolled. We analyzed computed tomography angiographies and quantified AAC scores by calculating the Agatston score for the abdominal aorta. The donors were stratified into the non-AAC group (AAC score = 0; n = 238) and the AAC group (AAC score >0; n = 49). The relationship between AAC and perioperative estimated glomerular filtration rate was analyzed. For the 180 donors consenting to implantation biopsy, the nephrosclerosis score was defined as the sum of abnormalities, including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. RESULTS: The mean AAC score was 185.5 ± 263.3 in the AAC group. The AAC group was older than the non-AAC group (51.1 ± 6.1 vs 37.9 ± 11 years; P < .001). Perioperative renal function was not different between the 2 groups. However, among the AAC group, donors with an AAC score of >100 were associated with delayed renal function recovery (P = .035). Donors with AAC were more likely to have glomerulosclerosis (50.0% vs 29.1%; P = .022), tubular atrophy (62.5% vs 33.1%; P = .002), and a higher nephrosclerosis score (P = .002). CONCLUSIONS: Living donors with an AAC score of >100 require close observation because they have a higher probability of delayed renal function recovery after donation. AAC is associated with nephrosclerosis in healthy adults.

The effect of external electron beam on neointima in rat carotid artery injury model.

PURPOSE: Endovascular irradiation with either a gamma or a beta source has shown to reduce neointimal proliferation. However, the effect of external-beam radiation on neointimal hyperplasia is controversial. The objective of this study was to determine the effect of external-beam irradiation with different doses on neointimal hyperplasia in the rat carotid artery injury model. METHODS AND MATERIALS: Twenty-seven Sprague-Dawley rats underwent endothelial denudation injury by 2F Fogarty balloons on carotid artery. Immediately after the injury, rats were irradiated externally using 6-MeV electrons. Rats were grouped according to the radiation doses, 0 Gy as controls (n = 5), 5 Gy (n = 5), 10 Gy (n = 5), 15 Gy (n = 6), and 20 Gy (n = 6). Then, rats were sacrificed after 2 weeks and the carotid arteries were perfusion-fixed in paraformaldehyde. External elastic lamina (EEL) area, lumen area, maximal intimal thickness (MIT), and intimal area (IA) of the injured segments were measured on the basis of histomorphometry. RESULTS: In EEL and lumen area, there was no statistically significant difference between the irradiated groups and the controls. In MIT and IA, low-dose radiation (5 Gy and 10 Gy) did not induce any significant reduction. High-dose radiation (15 Gy and 20 Gy), however, reduced MIT and IA significantly. CONCLUSION: External electron beam reduced the intimal area, and the inhibition of neointimal proliferation was dependent upon radiation doses. This study suggests that the minimal effective dose for the inhibition of neointimal hyperplasia following denudation injury in the rat carotid model is between 10 Gy and 15 Gy.

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum from 41 patients with untreated NSCLC (Stage: IIB, 3; IIIA, 6; IIIB, 17; IV, 15; HISTOLOGY: squamous cell carcinoma, 18; adenocarcinoma. 14; undetermined, 9). RESULTS: The median VEGF level was 312 pg/ml, ranging from 70 to 1440 pg/ml. Patients were divided into high VEGF (>312 pg/ml) and low VEGF (< or =312 pg/ml) groups using the median value as a cut-off. There were no significant associations between the serum VEGF levels and various clinicopathologic characteristics including age, gender, histologic type, stage and treatment. A significant positive correlation was found between serum VEGF levels and platelet counts (r=0.495; P=0.001). In addition, serum VEGF levels also correlated with leukocyte counts (r=0.478; P=0.002). In seven patients with measurement of follow-up serum VEGF levels at the end of treatment (chemotherapy and/or radiotherapy), the median serum VEGF level significantly decreased after the treatment (416 pg/ml; range, 96-812 pg/ml vs. 185 pg/ml; range, 49-487 pg/ml; P=0.028). However, the median platelet count (317,000/microl; range, 190,000-395,000/microl vs. 246,000/microl; range, 72,000-271,000/microl; P=0.028) and leukocyte count (10,000/microl; range, 8700-17,200/microl vs. 5100/microl; range, 3900-9500/microl; P=0.018) also decreased after the treatment. There was no statistically significant difference in the median survival of the patients between high VEGF group and low VEGF group (8 months vs. 9 months, P=0.647). CONCLUSIONS: Although serum VEGF level was significantly associated with platelet and leukocyte counts in NSCLC patients, it did not correlate with tumor burden and prognosis of the patients.

Characterization of human immunodeficiency virus type 1 integrase mutants expressed in Escherichia coli.

The eight mutant integrase (IN) proteins of human immunodeficiency virus type (HIV-1), which have a single point mutation at a highly conserved central region, were prepared, and characterized in terms of their endonucleolytic activities and disintegration activities in vitro. Mutation of two highly conserved amino acids, Asp116 or Glu152, leads to complete loss of both the activities, suggesting that these two amino acids are directly associated with enzymatic functions. In addition, the mutant of the position Ser147 was found to have highly depressed endonucleolytic activity showing that the reaction was very delayed in comparison with that of the wild type. However, significant disintegration was detected in the mutant Ser147, indicating that the enzymatic mechanisms of the endonucleolytic and disintegration activities are not exactly reverse. The integrase protein with a mutation at the conserved amino acid Asn117 or Gly118 had a slight loss of the endonucleolytic activity, while a mutation at the three positions, Tyr143, Ser153, and Lys159, had no detectable effect on their enzymatic activities. These results indicate that only a few of the conserved amino acids are critical for enzymatic activities.

Minimal core domain of HIV-1 integrase for biological activity.

The human immunodeficiency virus type-1 (HIV-1) integrase (IN) mediates insertion of viral DNA into human DNA, which is an essential step in the viral life cycle. In order to study minimal core domain in HIV-1 IN protein, we constructed nine deletion mutants by using PCR amplification. The constructs were expressed in Escherichia coli, and the proteins were subsequently purified and analyzed in terms of biological activity such as enzymatic and DNA-binding activities. The mutant INs with an N-terminal or C-terminal deletion showed strong disintegration activity though they failed to show endonucleolytic and strand transfer activities, indicating that the disintegration reaction does not require the fine structure of the HIV-1 IN protein. In the DNA-binding analysis using gel mobility shift assay and UV cross-linking method, it was found that both the central and C-terminal domains are essential for proper DNA-IN protein interaction although the central or C-terminal domain alone was able to be in close contact with DNA substrate. Therefore, our results suggest that the C-terminal domain act as a DNA-holding motive, which leads to proper interaction for enzymatic reaction between the IN protein and DNA.

Analysis of integration activity of human immunodeficiency virus type-1 integrase.

The integration activity of human immunodeficiency virus type-1 (HIV-1) integrase was characterized in vitro by using pre-processed oligonucleotide substrates. The highest level of integration activity was found at pH 6.5 to 7.0, while the endonucleolytic activity was highest at pH 7.4 to 8.0. Although the endonucleolytic and integration reactions are consecutive in retroviral integration, our result indicates that the optimal conditions of the two reactions are quite different. In addition, it is suggested that the endonucleolytic and integration steps can be separated by control of the cellular physiological state in retroviral therapy. Strong integration was detected in the presence of 0.5-10 mM Mn2+ ion, but weak integration at around 10 mM Mg2+ ion. This observation explains that the Mn2+ ion is preferred to the Mg2+ ion as a cofactor in the integration reaction. Although there was no sequence-specificity in the integration site of the target DNA, integration was found to frequently occur at particular regions of the target DNA. Furthermore, the mutant integrases such as Asp116, Ser147, and Glu152, which had been reported previously, were shown to lose integration activity completely, indicating that these residues are critically involved in catalytic action.

Measurement of radiation absorbed dose in endovascular Ho-166 brachytherapy using a balloon angio-catheter.

The purpose of this study was to estimate the absorbed dose distribution of Ho-166 endovascular beta irradiation using an angio-catheter. The liquid form of Ho-166 was produced at the Korea Atomic Energy Research Institute (KAERI) by an (n,gamma) reaction. Ho-166 has a half-life of 26.8 h and emits a high-energy beta particle with a maximum energy of 1.85 MeV. GafChromic film was used for the estimation of the absorbed dose of beta particles. A Co-60 teletherapy source and a 6 MV photon beam from a linear accelerator were used to generate dose-optical density calibration curves. The exposed films were read using a videodensitometer. With a modified micrometer, the film was positioned accurately on the surface of the balloon in water. The balloon was filled with Ho-166 solution to a pressure of 4 atm. Several film exposures were made with varying irradiation times and activities. The radiation absorbed dose rates were 1.02, 0.51 and 0.35 Gy x min(-1) x GBq(-1) x ml(-1) at the balloon surface, 0.5 and 1 mm from the balloon surface, respectively. The absorbed dose distribution revealed that Ho-166 is a good source for endovascular irradiation as the beta range is very short, avoiding unnecessary irradiation of normal tissue. A clinically applicable irradiation and duration of exposure were achievable utilizing our system.

Epicatechin inhibits radiation-induced auditory cell death by suppression of reactive oxygen species generation.

Radiation-induced toxicity limits the delivery of high-dose radiation to head and neck lesions. The aim of this study was to investigate the effectiveness of epicatechin (EC), a minor component of green tea extract, on radiation-induced ototoxicity in vitro and in vivo. The effect of EC on radiation-induced cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of hearing protection and drug toxicity of EC were explored in a zebrafish and rat model. Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI-OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. EC markedly attenuated the radiation-induced embryotoxicity and protected against radiation-induced loss and changes of auditory neuromast in the zebrafish. In addition, intratympanic administration of EC was protective against radiation-induced hearing loss in the rat model, as determined by click-evoked auditory brainstem (P<0.01). EC significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and cleaved PARP compared to their significant increase after radiation treatment. The results of this study suggest that EC significantly inhibited radiation-induced apoptosis in auditory hair cells and may be a safe and effective candidate treatment for the prevention of radiation-induced ototoxicity.

Comparison of enzymatic activities of the HIV-1 and HFV integrases to their U5 LTR substrates.

The human immunodeficiency virus type 1 (HIV-1) and human foamy virus (HFV) integrase proteins were overexpressed in Escherichia coli, and purified to a near homogeneity by one- or two-step purification scheme. The endonucleolytic, integration, and disintegration activities for the HIV-1 and HFV integrases were characterized in vitro. The endonucleolytic activities for the HIV-1 and HFV integrases were found only on their own substrates, respectively, indicating that the cognate U5 LTR sequences in the substrates is critical for specific cleavage. However, the integration and disintegration activities showed less specificity on the substrate usage. Our results suggest that the disintegration activity have more preference for substrates based on Y-shaped structure rather than on viral donor DNA sequence.

High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspects and results.

BACKGROUND: Radiation is essential for function preservation in the management of soft tissue sarcoma (STS). One of the advantages of brachytherapy is that it allows for specific localization of radiation dose to the tumor bed. We examined the results of our clinical experiences with immediate postoperative high dose rate (HDR) brachytherapy and external beam radiation treatment (EBRT) for STS. METHODS: A total of 17 patients (11 primary and six recurrent) between 1995 and 1999 were included in this review. The inclusion criteria for HDR and EBRT were as follows: (1) high-grade tumor, (2) low-grade tumor of > or = 10 cm, (3) recurrent tumor, (4) tumor abutting or invading critical structures and (5) positive margin. The catheters (six French) were placed parallel to the long axis of the tumor with a 1-1.5 cm spacing in between. If necessary, muscle or gel-foam was placed over the critical structures to maintain a minimum space of 0.5 cm from the catheters. On postoperative day 6, patients received HDR (2-3 Gy/fraction x6, twice daily). Three weeks later, patients received EBRT (total 36-60 Gy). The follow-up duration was between 13 and 60 months (median 31 months). RESULTS: There was no local failure within the radiation field in any of the patients. One patient required wound revision for delayed healing after brachytherapy. During EBRT, most patients experienced only mild erythema (grade 1 or 2 skin reaction). In long-term follow-up, there were no patients with neuropathy or significant fibrosis. CONCLUSIONS: Our results suggest that immediate postoperative HDR with a total dose of 12-18 Gy over 3 days is an effective treatment combined with EBRT in the management of STS.

A rat model for radiation-induced proctitis.

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.

Gallbladder adenomyomatosis: findings on MRI.

BACKGROUND: To describe the characteristic magnetic resonance imaging (MRI) findings of gallbladder adenomyomatosis in two cases. METHODS: Two patients had abdominal MRI findings of gallbladder adenomyomatosis confirmed at cholecystectomy. RESULTS: The surgical specimen showed findings typical of adenomyomatosis, including marked thickening of both epithelial and muscular elements with multiple Rokitansky-Aschoff sinuses. On gadolinium-enhanced spoiled gradient-echo images and single-shot fast spin-echo images, mild gallbladder wall thickening with multiple intramural cystic components from Rokitansky-Aschoff sinuses were readily visualized. CONCLUSION: Adenomyomatosis of the gallbladder can be detected and diagnosed from MRI findings.

Effect of transcatheter endovascular radiation with holmium-166 on neointimal formation after balloon injury in porcine coronary artery.

BACKGROUND: Neointimal formation in response to arterial injury is a major contributing element in restenosis after coronary balloon angioplasty and stenting. Endovascular irradiation has been reported to be effective in reducing restenosis. The purpose of this study was to investigate the effect of beta-emitting holmium-166 for the inhibition of neointimal formation in porcine coronary artery. METHODS AND RESULTS: A total of 34 pigs weighing 25 to 30 kg underwent oversized balloon injury (balloon/artery ratio, 1.3:1.4) at the proximal portion of the left anterior descending and circumflex arteries. One artery was randomly assigned to receive radiation after injury. Ho-166 was left in the balloon within the delivery catheter for a period sufficient to deliver 9 Gy and 18 Gy to a depth of 1 mm from the surface of the balloon. Four weeks later, pigs were sacrificed and hearts were perfusion-fixed, followed by histopathologic analysis and planimetry for measurement of maximal intimal thickness, intimal area, and fracture length. The coronary segment of the pigs in the control group had neointimal area of 1.18+/-0.55 mm2; the pigs in the 9-Gy group had neointimal area of 0.68+/-0.40 mm2 (P<.05 vs. control); and the pigs in the 18-Gy group had neointimal area of 0.29+/-0.12 mm2 (P<.01 vs. control). The maximal intimal thickness in the 18-Gy group (0.14+/-0.11 mm) was significantly reduced compared with the maximal intimal thickness in the control group (0.48+/-0.13 mm) (P<.01). CONCLUSIONS: Intracoronary radiation with liquid Ho-166 contained in a perfusion balloon catheter is feasible and effective in reducing neointimal formation after coronary overstretch injury in pigs. Therefore intracoronary irradiation on the injured segment may further reduce restenosis after balloon injury.

The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck.

BACKGROUND: The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients. METHODS: Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group. RESULTS: Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate. CONCLUSIONS: The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck.