Utility of Smart Arc CDR for intensity-modulated radiation therapy for prostate cancer

Volumetric-modulated arc therapy (VMAT) is a widespread intensity-modulated radiation therapy (IMRT) method, however, VMAT requires adaptation of the radiation treatment planning system (RTPS) and linear accelerator (linac); these upgrades are quite expensive. The Smart Arc of Pinnacle³ (Philips), which is the software used in VMAT calculations, can select constant dose rate (CDR) mode. This approach has a low initial cost because the linac upgrade is not required. The objective of this study was to clarify the utility of CDR mode for prostate IMRT. Pinnacle³ and Clinac 21EX linac (Varian, 10 MV X-rays) were used for planning. The plans were created for 28 patients using a fixed multi-field IMRT (f-IMRT), VMAT and CDR techniques. The dose distribution results were classified into three groups: optimal, suboptimal and reject. For the f-IMRT, VMAT and CDR results, 25, 26 and 21 patients were classified as ‘optimal’, respectively. Our results show a significant reduction in the achievement rate of ‘optimal’ for a CDR when the bladder volume is <100 cm³. The total numbers of monitoring units (MUs) (average ± 1σ) were 469 ± 53, 357 ± 35 and 365 ± 33; the average optimization times were ∼50 min, 2 h and 2 h 40 min, and the irradiation times were ∼280 s, 60 s and 110 s, respectively. CDR can reduce the total MUs and irradiation time compared with f-IMRT, and CDR has a lower initial cost compared with VMAT. Thus, for institutions that do not currently perform VMAT, CDR is a useful option. Additionally, in the context of patient identification, bladder volume may be useful.     

Measurement of Sterigmatocystin Concentrations in Urine for Monitoring the Contamination of Cattle Feed

This study aimed (1) at determining the levels of the fungal toxin sterigmatocystin (STC) in the feed and urine of cattle and (2) at evaluating the effects of supplementing the feed with a mycotoxin adsorbent (MA) on STC concentrations in urine. Two herds of female Japanese Black cattle were used in this study. The cattle in each herd were fed a standard ration containing rice straw from different sources and a standard concentrate; two groups of cattle from each herd (n = six per group) received the commercial MA, mixed with the concentrate or given as top-dressing, whereas a third group received no supplement and served as control. Urine and feed samples were collected at various time points throughout the experiment. STC concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-TMS). STC concentrations in straw were higher in Herd 1 (range 0.15–0.24 mg/kg DM) than in Herd 2 (range <0.01–0.06 mg/kg DM). In Herd 1, STC concentrations in urine significantly declined 2 weeks after replacing the contaminated feed, whereas MA supplementation had no effect. In conclusion, mycotoxins in urine samples are useful biological markers for monitoring the systemic exposure of cattle to multiple mycotoxins, as well as evaluating the effectiveness of interventions.     

Gastrointestinal stromal tumors with exon 8 c-kit gene mutation might occur at extragastric sites and have metastasis-prone nature

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the human gut. Most sporadic GISTs have somatic gain-of-function mutations of the c-kit gene. The mutations are frequently found at exon 11, sometimes at exon 9 and rarely at exon 13 or 17. Recently, exon 8 c-kit gene mutations were reported in very minor proportion of sporadic GISTs. We also found 3 GISTs with exon 8 c-kit gene mutations in approximately 1,000 sporadic GISTs examined. In the present report, we showed the clinicopathological data of those GISTs. One case had a deletion of codon 419 of aspartate, and 2 cases had a substitution of 3 amino acids of codon 417 to codon 419 to tyrosine. The former was the same mutation recently reported in 2 GIST cases, but the latter has not been reported in any GISTs. All three cases occurred at extragastric sites and two of three showed distant metastasis. Since the remaining case was regarded as high risk for recurrence, imatinib adjuvant treatment has been done without evidence of metastasis. Our results confirmed the idea that exon 8 mutations are minor but actually existing abnormalities in sporadic GISTs, and suggested that such GISTs have a feature of extragastric development and a metastasis-prone nature. Since the exon 8 mutations appeared to be really sensitive to imatinib as shown in the present case study, accurate genotyping including exon 8 of the c-kit gene is necessary in GISTs to predict response to imatinib in both the unresectable/metastatic and adjuvant settings.     

Arthrodesis of knee joint by vascularized fibular graft

Knee arthrodesis has been performed in 17 patients using vascularized fibular graft (VFG); 15 of them could be followed more than 1 year. Twelve were bone defect following tumor resection, two were traumatic bone defect, and one was intractable traumatic non-union. Three types of graft were performed; single VGF as supplement (Type I) in 5 cases, double VFG for femoral defect (Type II) in 8 cases, and double VFG for tibial defect (Type III) in 4 cases. Bone union was achieved in all cases except one. The average time to primary bone union was 4.7 months. Hypertrophy of the graft was observed significantly in some of Type II and in all of Type III. VGF is a useful method for knee fusion in patients with a large bone defect or with an intractable non-union. © 1996 Wiley-Liss, Inc.     

Antibodies to β2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Objective. To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to β₂-glycoprotein I (β₂GPI), and to search for a relationship between the presence of IgG and/or IgM anti-β₂GPI antibody and clinical manifestations in SLE patients. Methods. IgG and IgM anti-β₂GPI in 308 Japanese SLE patients were measured using phospholipid-independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. Results. The values of anti-β₂GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti-β₂GPI assay was more useful in distinguishing β₂GPI-dependent aCL from β₂GPI-independent aCL. The presence of IgG anti-β₂GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti-β₂GPI may fluctuate with disease activity. Conclusion. The results suggest that pathogenic aCL is directed against structurally altered β₂GPI and that enzyme immunoassay for anti-β₂GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.     

Diagnostic utility of programmed cell death ligand 1 (clone SP142) immunohistochemistry for malignant lymphoma and lymphoproliferative disorders: A brief review

The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune control and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and -negative subgroups, but their clinicopathological significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future.     

Significant association between high serum CCL5 levels and better disease‐free survival of patients with early breast cancer

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C‐C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead‐based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease‐free survival (DFS) of patients with high CCL5 levels (cut‐off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10‐0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis.     

Erythrocyte rosette inhibition as an assay for naturally occurring t lymphocytotoxic antibody in systemic lupus erythematosus

By means of a modified sheep erythrocyte rosette inhibition assay, we were able to detect naturally occurring lymphocytotoxic antibodies in sera from patients with systemic lupus erythematosus (SLE). The incidence of lymphocytotoxic antibodies was 86% in all SLE patients, and 100% in patients with active disease. Since this assay detects only the antibodies that react with the determinants on T cells or on both T and B cells, it has a great advantage of demonstrating in combination with appropriate absorptions the antibodies specific for T cells. When an appropriate panel of target cells was used, most of the antibodies in SLE sera as detected by this assay appeared to be analogous to a natural thymocytotoxic autoantibody (NTA) of New Zealand mice in its specificity and nature. The changes in the antibody titer of a patient with SLE during the course of disease correlated well with those in the total number of T cells in the blood, the antinuclear antibody titer, and some delayed skin hypersensitivities.     

Plasma Cholecystokinin Responses after Ingestion of Liquid Meal and Intraduodenal Infusion of Fat, Amino Acids, or Hydrochloric Acid in Man: Analysis with Region Specific Radioimmunoassay

A highly sensitive and precise radioimmunoassay system for plasma cholecystokinin (CCK) was developed with the anli-CCK-8 specific antiserum which raised against N-terminal amino acids residue of sulfated CCK-8 and reacted with CCK-8, CCK-33, and CK-39 but not with gastrin and its related peptides. Mean concentration of the fasting plasma CCK determined with this method using CCK-8 as standard was 12.9 ± 5.9 pg/ml in normal subjects (n = 26), and in patients with hepatic cirrhosis it was significantly higher (36.7 ± 16.9 pg/ml, n = 9, p < 0.01) than in normal subjects. In six young healthy volunteers, intraduodenal infusion of fat caused a significant increase ( p < 0.05) of plasma CCK from a basal level of 8.0 pg/ml to a peak of 43.0 ± 12.0 pg/ml at 20 min after starting of infusion. In the same subjects, a significant increase of plasma CCK was also observed by amino acids infusion, but no elevation of plasma CCK level was found during intraduodenal acidification.