[Quantitative evaluation of the burden of those giving home care for senile dementia of Alzheimer type subjects using the burnout scale of pines].

We quantitatively measured the physical and psychological burden of caregivers of 25 patients with senile dementia of Alzheimer type (SDAT). The Barthel Index (BADL, full score: 20 points) and the caregiver burden in terms of physical symptoms correlated well (r = -0.964, p < 0.001), as did the degree of abnormal behavior and caregiver burden in terms of psychological symptoms (r = 0.946, p < 0.001). The correlation with the burnout scale (BOS) of Pines was best when both factors of psychological and physical symptoms were included. The correlation between BOS and the caregiver burden in terms of both physical and psychological symptoms was r = 0.874, p < 0.001, and the correlation between BOS and "the degree of abnormal behavior" +(20- "BADL") was r = 0.853, p < 0.001. The burden in terms of physical symptoms increased as the BADL score decreased, but the burden in terms of psychological symptoms increased initially and decreased in the last phase of the disease. We conclude that the BOS score of SDAT caregivers was stable in the initial phase, then increased rapidly, thereafter preserved high, and dropped rapidly as the BADL score decreased.

Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hypopharyngeal carcinomas.

PURPOSE: DNA-dependent protein kinase (DNA-PK), a serine/threonine kinase composed of p470 catalytic subunit (DNA-PKcs) and p85/p70 heterodimer (Ku antigen), is considered a critical enzyme in the repair of the DNA double-strand breaks (DSB) that are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors. MATERIALS AND METHODS: We examined immunohistochemically the biopsy specimens of 44 patients with oropharyngeal carcinoma and 32 patients with hypopharyngeal carcinoma who had been treated with radiotherapy. RESULTS: Immunopositivity to Ku85 and DNA-PKcs was found in all patients. The staining of Ku85 and DNA-PKcs was nuclear, with none of the normal epithelial cells or malignant cells exhibiting cytoplasmic or membrane immunoreactivity. Normal epithelial cells were all stained intensely. In tumors, intense nuclear staining of DNA-PKcs was seen in 75 of 76 tumors, while that of Ku85 was seen in all 76 patients. The radiation responses of a primary tumor that was stained weakly with DNA-PKcs were excellent. CONCLUSION: Our results suggest the possibility of predicting the intrinsic radiosensitivity of human tumors in clinics able to perform immunohistochemical analysis of DNA-PK.

[Model of biological equivalent dose distribution modified by volume effect in radiotherapy].

This paper demonstrates that a biologically equivalent dose distribution including volume effect can be generated. Since the time-dose-fractionation (TDF) concept is convenient for comparing various radiation treatment schedules, TDF distribution maps are made on the basis of the physical dose distribution. On the other hand, the dose volume histogram is useful to evaluate volume effect, but is not necessarily an easy approach owing to the absence of spatial linkage. If distribution maps also representing the volume effect could actually be made, it would become easier to simultaneously predict both tumor control probability and the normal tissue complication rate. Because such tools should be very useful for planning radiotherapy, we proposed an experimental volume effect model. In this, one pixel is affected by all its surrounding pixels and the effect depends on the distance between pixels, volume, and the irradiated dose of another pixel. When the model was adapted to the conventional power law model, we could acquire a new equation with mathematical analysis. This permitted us to calculate the volume effect on each voxel within the treatment volume. Using a personal computer and treatment planning system, we calculated the "TDF-volume" distribution and drew maps based on this equation and the TDF values of each voxel for radiotherapy of a pelvic tumor.

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues.

BACKGROUND: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbs1 play a critical role in DNA DSB repair. METHODS: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbs1 in 134 specimens from various normal and tumor tissues with different radiosensitivity. RESULTS AND CONCLUSION: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbs1 was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbs1, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues.

Four cases of meningeal hemangiopericytoma treated with surgery and radiotherapy.

We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation.

Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index.

PURPOSE: Hyperfractionated and accelerated radiotherapy without a split was performed to improve the local control probability of early glottic carcinomas. We analyzed the results of this regimen by using the Ki-67 index. METHODS AND MATERIALS: Over a 12-year period, 85 T1N0M0 glottic cancers and 50 T2N0M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with accelerated fractionation (AF) since 1990. The CF program consisted of five daily fractions of 2 Gy per week, for a total of 64 Gy. The AF program consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, for a total of 55 or 58 Gy. The specimens, taken before radiotherapy, were immunohistochemically stained with anti-Ki-67 antibody. RESULTS: The 5-year local control probability for T1 tumors was 79.6 +/- 6.9% with CF treatment, whereas with AF it was 86.9 +/- 5.6%. For T2 tumors it was 62.7 +/- 12.2% with CF, whereas it was 74.7 +/- 7.8% with AF. The difference between CF and AF did not reach the point of statistical significance. However, when T1 tumors had a Ki-67 index lower than 50%, the local control rate achieved with AF was significantly better than that with CF (p = 0.018). When the tumors had a Ki-67 index that was 50% or more, there was no difference in the local control rate between CF and AF, whether they were T1 or T2. The peak mucosal reactions at the larynx and/or hypopharynx were much more severe and appeared at smaller doses and earlier in AF than in CF. The patients with AF showed no severe late complications. CONCLUSIONS: AF could not obtain statistically significant improvement in local control probability of T1 or T2 glottic carcinomas.

Spontaneously reduced midgut malrotation: CT diagnosis.

Midgut malrotation is a relatively rare congenital malformation that arises from an error of rotation and fixation of the midgut. We report a case of spontaneously reduced duodenal malrotation diagnosed by computed tomography and roentgenography after the ingestion of barium.

Prognostic factors of nasopharynx tumors investigated by MR imaging and the value of MR imaging in the newly published TNM staging.

PURPOSE: To examine the usefulness of MR imaging for predicting local control of nasopharyngeal carcinoma (NPC) and the value of MR imaging in the newly published fifth edition of the TNM classification. METHODS AND MATERIALS: We studied 29 patients with NPC with MR imaging and CT before and after treatment. Staging was done according to the fourth and newly published fifth editions of the International Union Against Cancer (UICC) staging system. The radiotherapy protocol was designed to deliver 66 to 68 Gy to the primary tumor and clinically involved nodes. RESULTS: MR proved better than CT at identifying obliteration of the pharyngobasilar fascia, invasion of the sinus of Morgagni, through which the cartilaginous portion of the eustachian tube and the levator veli palatini muscle pass, invasion of the skull base, and metastases to lymph nodes in the carotid and retropharyngeal spaces. All seven patients without invasion of the pharyngobasilar fascia had local control. The local control rates of patients with invasion of the skull base were not good (60 to 73%). There was no apparent relationship between tumor volume determined by T1-weighted MR images and local control when the tumor volume was more than 20 cc. The newly published N staging system appears to successfully identify the high-risk group for distant metastasis as N3. In our series, four of five patients with N3 disease developed distant metastases. CONCLUSION: Deep infiltration of the tumor is a more important prognostic factor in NPC than tumor volume. Since the newly published T staging system requires a search for tumor invasion into soft tissue such as parapharyngeal space and bony structures, MR imaging may be indispensable for the newly published NPC staging system.

Radiotherapy in the management of Graves' ophthalmopathy.

BACKGROUND: To report the results of radiotherapy for patients with failure, adverse reactions or relative contraindications to the use of steroids or immunosuppressants, by using newly developed quantitative indexes. METHODS: Fourteen female and six male patients with Graves' ophthalmopathy were treated with radiotherapy between 1989 and 1996. Prior to radiotherapy, eight patients received treatment with prednisone, four received immunosuppressants and four received a combination of both. Four patients with contraindications to steroids were initially managed with radiotherapy. Most of the patients received a dose of 24-28 Gy in 2 Gy fractions. We used the newly developed motility limitation index to assess extraocular motility. RESULTS: Treatment was well tolerated. There have been no late complications. All 12 patients with soft tissue signs such as edema, irritation, tearing and pain were improved. Proptosis did not improve or improved only slightly, 3 mm at best. However, proptosis in all but two has been stabilized and has not deteriorated in the follow-up period. Most of the patients have experienced an improvement of eye-muscle motility. Extraocular muscles that work for elevation were impaired more severely than the other muscles and this tended to remain. Of the 16 patients using steroids before or when radiotherapy was initiated, 15 were tapered off and only one patient required additional steroids, thus sparing the majority from steroid adverse reactions. CONCLUSION: Radiotherapy was effective in preventing exacerbations of active inflammatory ophthalmopathy in patients with Graves' disease with minimal morbidity and thus eliminated the adverse reactions associated with protracted corticosteroid use. The newly developed motility limitation index was useful in detecting delicate changes in motility of individual extraocular muscles.

Treatment of localized non-Hodgkin's lymphomas of the head and neck: focusing on cases of non-lethal midline granuloma.

This report clarifies the prognostic factors for survival in localized non-Hodgkin's lymphoma (NHL) of the head and neck and defines optimal regimens for this disease. One hundred-seven untreated patients with Stage I or II NHL of the head and neck were treated with involved field radiation therapy for orbital, nasal, or paranasal lymphoma and extended field radiation for Waldeyer's ring or neck lymphoma. Radiation doses were 39-48 Gy. In the latter half of the study, adjuvant chemotherapy was administered. Of 107 patients, 95 achieved complete response (CR). Of the 12 patients that did not achieve CR, 9 had nasal T-cell lymphoma (NTL) of the lethal midline granuloma type (LMG-NTL). Only one patient who obtained CR relapsed in a previously irradiated area. Age, sex, stage, bulky mass, number of involved sites, LMG-NTL, histologic subtypes, radiation dose, and adriamycin dose were analyzed for prognostic significance for disease-specific survival in NHL by multivariate analysis. LMG-NTL was the most significant prognostic factor (P < 0.001). Patients with higher age also experienced a higher relative risk than patients of > or =60 years of age (P = 0.0063). Dose of adriamycin reached the borderline significance (P = 0.0600). Radiotherapy is excellent for obtaining local control of head and neck NHL. Randomized trials are required to determine the appropriate radiation field and dose in patients previously treated with chemotherapy. LMG-NTL and age were the significant prognostic factors for disease-specific survival.

Mucoepidermoid carcinoma of the larynx: a case which responded completely to radiotherapy and a review of the literature.

Most laryngeal cancers are squamous cell carcinomas, and adenocarcinomas account for < 1% of cancers of the larynx. Among them, mucoepidermoid carcinoma is extremely rare and there is little agreement about the treatment of this carcinoma. We encountered one patient with mucoepidermoid carcinoma of the bilateral vocal cords (T1bN0M0, Stage 1). For this, most investigators recommended a surgical procedure. However, because of his old age, the early stage and low grade of histopathology, we treated this patient with radiotherapy alone, delivered by accelerated hyperfractionation, which is a more effective strategy for treating radioresistant tumors than conventional irradiation. Following radiotherapy, the tumor disappeared and the patient has been alive and well for more than six years. An old patient with mucoepidermoid carcinoma of the larynx was successfully treated with radiotherapy alone.

Diagnosis and treatment of malignant lymphoma of the parotid gland.

BACKGROUND: To correlate the imaging and pathological features and to discuss therapeutic modalities and the prognosis of malignant lymphoma originating in the parotid gland, which is relatively rare. METHODS: The subjects were five patients with malignant lymphoma originating in the parotid gland. Three and two patients were stage I and stage II, respectively. CT examination was applied to all, whereas only one case was examined by MRI. All were treated with radiotherapy following surgery or chemotherapy. Three patients underwent combination chemotherapy, such as with MACOP-P or VEPA, following surgery. RESULTS: Although malignant lymphoma originating in the parotid gland is histologically described as low-grade non-Hodgkin's lymphoma, two and one of the cases were classified as intermediate and high grade in the present series, respectively. These three exhibited a tendency for infiltration into the adjacent tissue and tumor inhomogeneity in the imaging findings, suggesting a correlation with histologically intermediate or high-grade non-Hodgkin's lymphoma. It was successfully controlled by radiotherapy, with dosages ranging from 40 to 44 Gy. The patients were followed for 2-8 years. No relapse was found in the three patients with stage I. However, both stage II patients had relapses and were subjected to additional radiotherapy combined with chemotherapy. Since then, no tumor relapse has been noted at either this or other sites. CONCLUSIONS: Malignant lymphoma including intermediate or high grade originating in the parotid gland indicated satisfactory prognosis following radiotherapy and chemotherapy.

Radiotherapy for Kimura's disease: the optimum dosage.

PURPOSE: To evaluate retrospectively the optimum dosage of irradiation for Kimura's disease. METHODS AND MATERIALS: Twenty patients with Kimura's disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS: At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS: Radiotherapy is an effective treatment for Kimura's disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

The effect of radiation on the expression of intercellular adhesion molecule-1 of human adenocarcinoma cells.

PURPOSE: To investigate the changes in antigenic expression of intercellular adhesion molecule-1 (ICAM-1) caused by ionizing radiation of cultured human adenocarcinoma cells. METHODS AND MATERIALS: Human colonic BM314 and gastric MKN45 adenocarcinoma cells were irradiated to investigate the expression of ICAM-1 on the cell membrane and in the supernatant. In addition, the ICAM-1 gene expression (mRNA) was analyzed using a ICAM-1 cDNA as a probe. RESULTS: The expression of ICAM-1 on the membrane was found to increase by irradiation. This effect was also observed in the supernatant. In addition, the irradiated cell population showed slight, but clear increases in ICAM-1 mRNA expression. CONCLUSIONS: These results show that the enhancement of expression of ICAM-1 by radiation takes place at the ICAM-1 gene expression (mRNA) level. The results suggest that the low dose radiation may be useful for accumulating LFA-1 positive cytotoxic T lymphocytes (CTL) at the local tumor tissue, by which tumor cells may be attacked.

Long survival of patients with unresectable cervical carcinoma after radiotherapy.

We report our experience with radiotherapy for three patients with cervical carcinoma in whom surgery had been downgraded to the performance of exploratory laparotomy only, because of extensive primary tumor or nodal invasion to the surrounding organs and vessels. Tumor invasion to the bladder, side wall invasion or unresectable nodal disease at the time of exploration prevented definitive surgery in our case series. After laparotomy, we carried out radiation therapy consisting of external irradiation to the pelvis and intracavitary irradiation with high dose rate 60Co or low dose rate 137Cs sources. Local and regional control was obtained in all three patients, and there was no locoregional recurrence during > 5 years of follow-up. One patient died of paraaortic lymph node metastases, but she had no pelvic recurrence. Several authors have reported an increased risk of small bowel obstruction in patients who undergo laparotomy before radiotherapy. None of our patients developed small bowel obstruction, although one had anal bleeding which was cured by conservative therapy. Radiotherapy was effective for locoregional control in all three patients with unresectable cervical carcinoma.

Radiotherapy of vertebral hemangiomas.

Between 1975 and 1996, 14 patients (11 females, 3 males) with vertebral hemangioma received treatment with radiotherapy. Thirteen patients had a history of back pain or lumbago and 2 patients had neurological symptoms such as sensory impairment or paraplegia. The standard dose administered was 36 Gy in 18 fractions (five treatments per week). In the 13 patients with pain, this was completely or partially relieved. The condition of a man with hypesthesia of the legs deteriorated and a woman with paraplegia who was treated with decompressive laminectomy followed by radiotherapy recovered completely after irradiation. CT scan before irradiation showed thickened trabeculae as small punctate areas of sclerosis in all patients. At MR imaging before irradiation, T2-weighted MR images showed areas of high intensity in all patients and MR images demonstrated lesion enhancement. However, none of the patients who were treated successfully with radiation demonstrated any changes of the affected vertebra in the conventional radiographic films. CT scan or MR imaging, even 5 years after irradiation. Radiological imaging is indispensable for the diagnosis of vertebral hemangiomas but does not appear to be useful for evaluating the effects of radiotherapy.

Retropharyngeal abscess after radiation therapy and cis-platinum, 5-fluorouracil treatment for nasopharyngeal carcinoma with collagen disease: report of two patients and a review of the literature.

Collagen disease are frequently associated with malignant tumors. Recently, radiotherapy combined with chemotherapy has been recommended for improving the efficacy of treatment for nasopharyngeal carcinoma. Two patients with nasopharyngeal carcinoma complicated by collagen diseases (dermatomyositis in one, and Sjögren's syndrome with mixed connective tissue disease in the other) were given radiotherapy combined with chemotherapy consisting of cis-platinum and 5-fluorouracil. Following this combination therapy, both patients developed retropharyngeal abscess and ulceration of the mucosal membrane on the posterior wall of the oropharynx; there was no tumor cell involvement. Because these injuries were more severe than would have been expected from radiotherapy alone, it is recommended that special attention be paid to combination therapy in patients with nasopharyngeal carcinoma complicated by collagen disease.

Results of cesium needle interstitial implantation for carcinoma of the oral tongue.

One hundred thirty previously untreated patients with invasive squamous cell carcinoma of the oral tongue received interstitial radiotherapy with curative intent using cesium needles. Ninety-nine patients were treated with interstitial radiotherapy alone and 31 patients received interstitial radiotherapy combined with external beam irradiation. The recurrence-free rates in the primary lesions were 94.4% (17/18) in T1, 91.2% (52/57) in T2, and 70.9% (22/31) in T3 lesions. The local recurrence-free rates with single-plane and two-plane implantation were good: 89.7% (70/78) and 85.7% (12/14), respectively. The rate of 64.2% (9/14) for volume implantation was significantly poorer (p < 0.05). It is evident that tumor volume is an important factor in the control of cancer following interstitial therapy. The overall incidence of ulceration of the tongue and mandibular complication was 20% (26/130) and 13% (17/130), respectively. Using both interstitial and external radiotherapy, the incidence was 22.5%, compared with 10.1% using interstitial radiotherapy alone. The mandibular complication incidence of 8.9% with single-plane implants was much lower than 20.8% for two-plane and 23.5% for volume implants. Interstitial radiotherapy is most suitable in T1 and T2 cases in which single-plane implantation is possible; for these patients interstitial radiotherapy, which has the advantage of preserving the structure and function of the tongue, should continue to be used in the future in spite of the progress in reconstructive surgery.

Effect of radiation on the expression of carcinoembryonic antigen of human gastric adenocarcinoma cells.

The changes of antigenic expression of cultured human gastric adenocarcinoma MKN45 cells caused by irradiation were investigated to elucidate the immune responses to localized irradiation. The expression of carcinoembryonic antigen (CEA) showed remarkable increases in the culture supernatant and on the surface of the membrane of irradiated cells. The expression of major histocompatibility complex Class I antigen on the membrane also was enhanced by irradiation. In addition, the irradiated cell groups, when analyzed using a CEA-specific probe, showed remarkable increases in the CEA mRNA. These enhancements increased in the 10-Gy and 15-Gy irradiated populations compared with the 5-Gy irradiated population. These results suggest that the enhancement of expression of CEA by radiation takes place at the CEA gene expression (mRNA) level but not at the protein level.