Efficacy of the Mirasol pathogen reduction technology system against severe fever with thrombocytopenia syndrome virus (SFTSV).

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4.11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV.

Parallel comparison of apheresis-collected platelet concentrates stored in four different additive solutions.

BACKGROUND AND OBJECTIVES: Partially replacing plasma with additive solutions in platelet (PLT) concentrates (PCs) may help to reduce transfusion reactions. Constituents of PLT additive solutions (PASs) have been revealed to affect the quality of PCs. Previous studies involved pairwise comparison of identical PLTs with two different PASs or multicomparison using random PLTs with three or more PASs. In this study, we performed parallel comparison using PCs from identical donors with four PASs. In addition to traditional parameters, the release of bioactive substances and plasma proteins was assessed. MATERIALS AND METHODS: Platelets collected four times by apheresis from three donors were suspended in Intersol, SSP+, Composol or M-sol with 35% autologous plasma. The PC parameters, including PLT activation markers, glucose consumption, chemokines and plasma proteins, were assessed during 5-day storage. RESULTS: Mean PLT volumes were decreased in SSP+, Composol and M-sol after 5-day storage, with significant differences, whereas the hypertonic shock response (HSR) was decreased only in Intersol. Glucose consumption was faster in Intersol and M-sol than in SSP+ or Composol. PLT activation, determined as CD62P, sCD62P, sCD40L and RANTES, was significantly higher in Intersol than the other three PASs. No marked change was observed in fibrinopeptide A and C3a in any PASs. CONCLUSIONS: M-sol, SSP+ and Composol effectively preserved the quality of PCs. PLT activation was significantly enhanced in Intersol compared with the other three PASs. These effects seem to depend on magnesium and potassium as a constituent. Parallel comparison further verified that the PC quality largely depended on PASs but not donors.

Radiation therapy for early glottic cancer (T1N0M0): I. Results of conventional open field technique.

From November 1977 through April 1982, a total of 91 patients with glottic cancer (T1N0M0) were treated with the open field technique of 4 MV X ray using bilateral parallel-opposed fields. Total radiation dose administered was 60 Gy in 30 fractions over a 6-week period. Actuarial 5-year disease-free survival rate was 89%. Significant prognostic factors of local control were tumor length (p = 0.021), tumor width (p = 0.001), tumor type (p = 0.004), tumor response to irradiation at 40 Gy (p = 0.000) and 60 Gy (p = 0.000) by chi-square test. Ultimate local control rate by radiation therapy and salvage surgery was 97% and voice preservation rate was 91%.

Radiation therapy for early glottic cancer (T1N0M0): II. Prospective randomized study concerning radiation field.

A prospective randomized study to determine the effect of radiation field on the local control of early glottic cancer was performed. From May 1982 through December 1985, a total of 87 patients with early glottic cancer (T1N0M0) were treated at our department with an individualized wedge filter technique using a shell to improve the dose distribution and immobilization during radiotherapy with 4 MV X ray. Patients were randomly allocated to either treatment group A (radiation field size: 5 x 5 cm2) or B (6 x 6 cm2) using bilateral parallel opposed portals. Total radiation dose administered was 60 Gy in 30 fractions over a 6-week period. The 3-year recurrence-free survival rates were 93% in group A and 96% in group B (no significant difference). Comparison with historical control showed that both arms achieved better results. These results were mainly due to the improved local control of whole-length lesions of single vocal cords. Acute mucosal reaction (p less than 0.05) and persistent arytenoid edema lasting more than 6 months (p less than 0.02) were more frequently observed in group B than in group A. It is concluded that the critical factor in getting optimal results in the treatment of early glottic cancer is careful attention to the technique of treatment.

High-dose rate intracavitary therapy for carcinoma of the uterine cervix: II. Risk factors for rectal complication.

From August 1978 through December 1982, a total of 267 patients with carcinoma of the uterine cervix were treated using remote afterloading high-dose rate intracavitary therapy (RALS) with non-rigid applicator at our department. The data from 199 previously untreated patients with standard application out of 267 were available for this analysis of rectal complication. The incidence of moderate to severe rectal complication (Kottmeier's grade 2 and 3) was 7% (13/199). Cox's regression model was used for the analysis of risk factors for rectal complication in which even minor injuries (grade 1) were included. By using this method, it was clear that the first significant risk factor was z-coordinates of weighted geometric center (WGC-z) (p = 0.0007) and the second corresponding factor was rectal TDF (p = 0.0082), the sum of the rectal dose measured by semiconductor dosimeter (ICD-5) and the dose of external whole pelvic irradiation. From the analysis of application pattern of intracavitary sources, WGC-z indicated the approximation of intracavitary sources to the anterior wall of rectum quantitatively and three-dimensionally. The significance of rectal TDF also implied that the monitoring of rectal dose by ICD-5 had an important role for the prediction and prevention of rectal complication after RALS.

High-dose rate intracavitary therapy for carcinoma of the uterine cervix: I. General figures of survival and complication.

From August 1978 through December 1982, a total of 200 patients with previously untreated carcinoma of the uterine cervix were treated using remote afterloading high-dose rate intracavitary therapy (RALS) at our department. According to the staging of UICC (1978), 8 patients were classified into Stage Ia, 22 Ib, 22 IIa, 53 IIb, 85 III, and 10 IV. Actuarial 5-year survival rates by Stage were 100% in Stage Ia, 86% Ib, 67% IIa, 72% IIb, 41% III, and 20% IV (p = 0.0001). Significant prognostic factors in Stage II were the value of hemoglobin (p = 0.0115) and age (p = 0.0431) by logrank test. Corresponding factors in Stage III were the value of hemoglobin (p = 0.0005) and total protein (p = 0.0036). Late complications after RALS developed in 22 patients (11%), that is, rectum 14 (7%), bladder 6 (3%), small intestine 4 (2%) and sigmoid colon 1 (1%). Severe complications requiring surgery were noted in 7 patients (4%). There was no fatal case attributable to complication. It is concluded that RALS is one of the most effective and safe means for the treatment of carcinoma of the uterine cervix based on our results.

Percutaneous brachytherapy for small-sized non-small cell lung cancer.

A patient with a small-sized pulmonary adenocarcinoma was successfully treated by percutaneous high dose rate interstitial brachytherapy alone. The patient, who had an adenocarcinoma with 12-mm diameter in the lingular lobe of left lung, was judged to be inoperable because of poor pulmonary function due to emphysema and extensive pleural adhesion. The tumor was punctured with a 21-gauge fine applicator needle followed by the introduction of an iridium 192 (192Ir) radioactive source through the applicator needle using a remote afterloader. The tumor was irradiated for 225.1 s in one fraction. The tumor was in the inside of the iso-dose line of 40 Gy. The delivered doses calculated at nine reference points, which were 12.5 mm distant from the center of the tumor, distributed between 19.225 and 32.169 Gy, with a mean of 24.8 Gy. No apparent side effect including pneumothorax and hemoptysis was observed. The tumor shrank and showed no increment of the size for about 2 years.

Radiation therapy of the para-aortic lymph nodes in carcinoma of the uterine cervix: the concurrent use of cimetidine to reduce acute and subacute side effects from radiation.

A prospective study of the effects of radiation therapy (RT) on para-aortic lymph nodes in uterine cervical cancer was conducted. As part of the study, cimetidine (800 mg daily) was administered during RT to relieve and prevent adverse reactions of the gastrointestinal tract caused by RT. In half of the patients, cimetidine (400 mg daily) was continued after RT was finished. The RT field was 7 to 8 cm wide and covered the area from the 4th lumbar to 11th thoracic vertebrae. The total dose administered was 45 Gy in 25 fractions over a five-week period. From September 1986 through October 1987, 89 patients were entered in this study. During RT, only slight gastrointestinal symptoms, such as nausea, vomiting, appetite loss, fatigue, and epigastralgia, were observed. These symptoms increased when cimetidine was withdrawn, but not in the patients who continued to receive cimetidine. It is concluded that cimetidine during and after RT can reduce the acute and subacute side effects of RT.

Radiation therapy for carcinoma of the hypopharynx with special reference to nodal control.

From October 1977 through December 1983, 61 patients with carcinoma of the hypopharynx were treated with radiation therapy (RT) and surgery or with RT alone. Five-year survival rates by N-stage, according to the TNM classification by UICC (1978), were 52% for N0 cases, 23% for N1, and 17% for N2-3 (N1 vs. N2-3, not significant). For N1-3 cases, corresponding figures by level of cervical nodal involvement by UICC (1978) were 29% for level 3 cases, 15% for level 2, and 8% for level 4 (level 3 vs. level 4, p less than 0.04). Therefore, the level of cervical nodal involvement was a more useful prognosticator for patients with nodal metastasis than the N-stage. Effective nodal control for patients with clinically positive nodes (N1-3) was obtained with a combination of neck node dissection and RT of 50 Gy or more. For N0 cases, elective RT of 50 Gy or more, encompassing an adequate field, was required.

Antibody response against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) in nasopharyngeal carcinoma.

Specific antibody responses against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) were evaluated. Thirty-five sera from pretreatment patients of nasopharyngeal carcinoma (NPC) and 12 from healthy adults were tested. Although the anti-EBNA2 response did not show any correlation with T stage, overall stage, or histopathology, it showed a correlation with the N stage of the disease. In a serological follow-up study, 17 (85%) of 20 patients showed a correlation on the change of antibody levels to EBNA2 and clinical progression. This suggests that EBNA2 serology might represent a useful marker relative to tumor status.

Proper use of serum antibody titres against Epstein-Barr virus in nasopharyngeal carcinoma: IgA/virus capsid antigen for diagnosis and EBV-related nuclear antigen-2 for follow-up.

Sera from patients with nasopharyngeal carcinoma (NPC) show high titres of IgA antibodies to Epstein-Barr viral capsid antigen (IgA/VCA). We reported previously that the serum titres for Epstein-Barr virus-related nuclear antigen-2 (EBNA2) correlated with NPC patients' prognosis. To investigate which is better for diagnosing NPC and predicting patient prognosis, the titration of serum IgA/VCA or EBNA2, we examined the same serum titres. Sixteen cases of NPC in which serum EBNA2 antibody titres had been tested, were investigated for the serum IgA/VCA antibody titres before and after radiation treatment. All NPC cases showed positive reactions with indirect immunofluorescence staining, and the median titre was 252. Twelve normal controls, 5 mesopharyngeal carcinoma patients, 4 hypopharyngeal carcinoma patients, 4 laryngeal carcinoma patients and 6 malignant lymphoma were also examined, but they showed negative or relatively low titres. A follow-up study revealed that IgA/VCA titres remained mostly stable. These results indicate a close relationship between IgA/VCA and NPC, however, prognosis correlated better with EBNA2 titres than with IgA/VCA titres.

Radiation therapy for primary non-Hodgkin's lymphoma of the head and neck.

From October 1977 through September 1986, a total of 77 patients (Stage I, 26; II, 35; and III-IV, 16) with primary non-Hodgkin's lymphoma (NHL) of the head and neck were treated with radiation therapy and chemotherapy (CVP or CHOP regimen) or radiation therapy alone. Actuarial 5-year survival rates by stage were 79% in Stage I, 35% in II, and 8% in III-IV. Significant prognostic factors were clinical stage (p = 0.0001), histological grade by the Working Formulation (p = 0.0089), and surface marker (T and B cell analysis) (p = 0.0001). In Stage II patients, the serum lactate dehydrogenase (LDH) level (p = 0.0286), the number of cervical lymph nodes involved (p less than 0.03), and maintenance chemotherapy after initial treatment (p = 0.0077) were significant prognostic factors. In conclusion, more intensive chemoradiotherapy is necessary as the first-line treatment in those with poor prognosis, especially those with T-cell type and high grade histology. In addition, maintenance chemotherapy after initial chemoradiotherapy is very important for Stage II NHL patients, especially those with a high LDH value or multiple cervical lymph node involvement.

Prognostic factors for patients with esophageal cancer treated with radiation therapy in PCS: a preliminary study.

PURPOSE: We investigated the prognostic factors, with special reference to age, for esophageal cancer patients, who did not receive surgery but were treated with radiation in the context of a Patterns of Care Study (PCS) in Japan. PATIENTS AND METHODS: The fifth PCS database format employed in the United States was used to collect information on 455 esophageal cancer patients by external audit. The data of patients who had not received surgery (n=252) were further selected and divided into two age groups, patients 75 years old or older (n=90) and patients younger than 75 years (n=162). Cox's proportional hazards model was used for the statistical analysis, with crude survival as the endpoint. Variables tested were age; Karnofsky performance status (KPS); history of pulmonary disease, cardiovascular disease, and diabetes; AJCC stage; external dose; treatment period; combination with chemotherapy; utilization of brachytherapy, and stratification of institutions. RESULTS: Statistically significant prognostic factors for all patients in the non-surgery group were KPS p=.0001), stage (p=.0001), and utilization of brachytherapy (p=.0102). For younger patients, KPS (p=.0001), stage (p=.0007), external dose (p=.0001), and utilization of brachytherapy (p=.0034) were significant, and for the elderly, stage (p=.0001) and external dose (p=.0006). CONCLUSION: Although this was a preliminary study, age was not a significant prognostic factor for esophageal cancer patients in the non-surgery group, and making the external dose more than 60 Gy appears to be effective for improving survival of elderly as well as younger patients.

[The state of the art: radiation therapy for non-small cell lung cancer].

The standard radiation schedule for non-small cell lung cancer is conventional fractionated 60-70 Gy/6-7 weeks in Japan, while a split-course or hypofractionated schedule is also used in some institutions in other countries. Hyperfractionated radiotherapy with/without chemotherapy is increasing while no definitive treatment schedule has been established as a standard treatment method. Dose escalation study by 3D-conformal radiotherapy is also an attempt at a breakthrough of radiotherapy in unresectable non-small cell lung cancer.

[Treatment of head and neck cancer: radiation therapy].

Radiation therapy is an effective modality for curative treatment with organ preservation, palliative treatment for pain control and combined/prophylactic treatment for local-regional control after surgery in head and neck cancer. For early lesions, 70-90% of local control may be expected in radiation therapy. However, some hurdles must be cleared with regard to advanced lesions. We reviewed the prospective randomized controlled trials (phase III trial) concerning adjuvant chemotherapy and multiple fractions per day of radiotherapy for advanced head and neck cancer. Adjuvant chemotherapy may be used in three ways in the treatment, i.e., induction therapy, concomitantly with radiotherapy and maintenance therapy. We reviewed the former two treatments because no "pure" phase III trial could be found in maintenance therapy after radiotherapy. As for multiple fractions per day of radiation therapy, the following definition is used. Hyperfractionation: Total dose is increased; dose per fraction is reduced; fractian number is increased,; overall time is relatively unchanged. Accelerated fractionation: Overall time is reduced; number of fraction total dose, and dose per fraction are either unchanged or somewhat reduced, depending on the extent of overall time reduction. Adjuvant chemotherapy combined with radiotherapy and multiple fractions per day of radiotherapy have been attempted to increase local-regional control and survival in a few randomized studies. However, these survival results were disappointing despite good local control. We need a more effective chemotherapy regime, fractionation schedule and also to clarify the indications for these treatments by analyzing the prognostic factors.

[Indication and problems of radiation therapy of elderly patients with cancer].

The incidence of cancer and the patients treated with radiation therapy increased with age. Of 5778 patients treated with radiation therapy at the Center for Adult Diseases, Osaka, 37.5% are over 65, and 10.8% are over 75 years old. Older patients with cancer have a lower survival rate. Patients over the age of 75 with carcinoma of the pharynx, esophagus, lung, and uterine cervix have decreased survival compared with younger patients. However, for the patients with carcinoma of the larynx, age is not a determinant of prognosis. With respect to radiation therapy, it is not clear whether elderly patients differ from younger ones in responsiveness. However, a decreased tolerance for radiation therapy might be expected and under-dosing with radiation therapy may be more prevalent. More study of the optimal management of elderly patients with cancer is needed.

[Cis-diamminedichloroplatinum (CDDP)-radiation therapy in nasopharyngeal carcinoma].

Between July 1977 and October 1983, 40 patients with nasopharyngeal carcinoma were treated by radiation therapy. From the investigation of this series, prophylactic treatment for distant metastases was recommended for good prognosis. Between November 1983 and May 1985, 10 patients with nasopharyngeal carcinoma were treated using a combination of cis-diamminedichloroplatinum (CDDP) and radiation therapy. Treatment results showed complete response in all 10 patients. One patient failed in the out field of boost therapy after whole-neck irradiation. This patient has shown no distant metastases. The remaining 9 patients have been controlled well. Major side effects were renal toxicity, and nausea and vomiting, which were mostly transient. However, severe mucositis of the oral cavity was observed in 4 patients (40%) of the CDDP-radiation group in contrast with 3 patients (8%) of the radiation-therapy-only group (p less than 0.01).

[Local control after radiation therapy for T1N0M0 glottic carcinoma].

From 1978 through 1984, we had 151 patients with T1N0M0 glottic carcinoma. They were treated by radiotherapy with 4MV x-ray in parallel opposing field of 5 X 5 cm2 or 6 X 6 cm2. The total dose was 60 Gy/30 fractions/6 weeks. The local control rate was 88.1%, the local recurrence being noted in 18 cases (11.9%). Of these 18 cases, 6 underwent partial laryngectomy, and 10 total laryngectomy. The remaining two cases died: one refused further treatment for recurrence and the other died in spite of total laryngectomy due to recurrence after partial laryngectomy. The salvage rate was 94.1%. The cumulative survival rate was 82.6% in Tla, 71.5% in Tlb and 81.1% in 151 T1N0. The tumor response was poor in the presence of lesion occupying the whole length of the vocal cord. Also, in the cases with ulcer formation or thickened vocal cord as seen on laryngogram, local control rate was not good. Better results will be achieved by improving treatment techniques, specially by improving dose-distribution by wedge-filtered technique and method for immobilization in plastic shell during radio-therapy.

[Radiation therapy of early glottic cancer (T1N0M0); retrospective review of historical control].

From November 1977 through April 1982, a total of 91 patients with early glottic cancer (T1N0M0) were treated with the open field technique of 4 MV X-ray using parallel opposed fields in bandage. Radiation dose administered was 60 Gy in 30 fractions over 6-week periods. Actuarial 5-year disease-free survival rate was 88.7%. Significant prognostic factors of local control were tumor length, tumor width, tumor type, tumor response at 40 Gy and 60 Gy. Ultimate local control rate by salvage surgery was 97% and voice preservation rate was 91%.