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M Kokubo

Publications and source records attributed to M Kokubo.

At least 19 recordsLinked to original sources

Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities.

PURPOSE: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved.

Adolescent↗

The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy.

PURPOSE: To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS: Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patient's body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patient's abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS: Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS: The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.

Adolescent↗

Meningeal carcinomatosis in patients with breast cancer: report of 8 patients.

BACKGROUND: Meningeal carcinomatosis (MC) is an uncommon but aggressive complication of advanced breast cancer with a recently increasing incidence. Although the prognosis is extremely poor for MC patients, early diagnosis and appropriate treatment are important. SUBJECTS AND METHODS: We reviewed 8 cases of MC from breast cancer at Kyoto University Hospital from 1990 to 1999. The median age was 51.5 years. All patients had widespread systemic metastases when diagnosed with MC. clinical symptoms were categorized into 3 groups: cranial nerve symptoms, spinal nerve symptoms, and other symptoms. Imaging studies were positive for MC in only 4 patients. Initial CSF cytology studies were positive in 4 patients, and repeated CSF cytology yielded positive results in the remaining 4 patients. Thus the median interval between the onset of any clinical symptom of MC and the initiation of treatment was 22.5 days (range 7 to 120 days ). All patients received whole brain radiotherapy (WBRT). Four patients were given intrathecal chemotherapy and/or intrathecal immunotherapy in addition to WBRT. RESULTS: Improvement of cranial nerve symptoms, spinal nerve symptoms, and other symptoms were observed in 3/5, 1/3, and 5/7 patients, respectively. Patients with cranial nerve symptoms who started WBRT within 29 days of the onset of the symptoms showed at least partial recovery whereas patients who started WBRT later showed no recovery. The median survival was 123 days (53 to 310 days). MC was the direct cause of death in 1 of 8 patients. CONCLUSION: When MC is clinically suspected, neither a negative imaging study nor a single negative CSF cytology can rule out MC. Prompt initiation of WBRT with or without intrathecal chemotherapy may be important for recovery from cranial nerve symptoms.

Adult↗

A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy.

We report a case of a 28-year-old woman with right-sided breast cancer. The patient had been treated for atopic dermatitis since her infancy. She underwent breast-conserving surgery (BCS) in July 1998, and three titanium clips were placed at the margin of the excision cavity at the time of surgery. Two months after surgery, the patient exhibited a rapid exacerbation of atopic dermatitis. Various drugs were suspected to be the cause of the allergic reaction, but the results of a bi-digital O-ring test (BDORT) suggested an allergic reaction to titanium clips. In August 1999, the patient underwent a second operation to remove the titanium clips under local anesthesia. Allergy to surgical titanium clips is a rare complication, but in patients with a history of severe allergic diseases, a preoperative immunologic examination should be performed and the patient's history of metal allergy should be investigated.

Adult↗

Results of breast-conserving therapy for ductal carcinoma in situ: the Kyoto University experiences.

BACKGROUND: The purpose of this study was to evaluate the results of breast-conserving therapy (BCT), defined as the combination of breast-conserving surgery with axillary dissection and definitive radiation therapy for ductal carcinoma in situ (DCIS). METHODS: Between November 1987 and March 1998, 33 patients with DCIS undergoing BCT at our hospital were examined. The mean age was 48. All patients underwent quadrantectomy or wide excision as well as axillary dissection. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was given to 15 patients with close or positive margins. Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. RESULTS: The minimum and median follow-up periods were 32 and 80 months, respectively. All patients but one were followed. Only one patient had a non-invasive local recurrence, 23 months after her operation. This patient was salvaged with simple mastectomy. Her prognostic index score was 8. The five-year local control rate was 97%. No serious acute or late complications were noted. CONCLUSION: The results of this retrospective study substantiate favorable data and appear to confirm the efficacy and reasonable local recurrence rate of BCT for the treatment of DCIS.

Adult↗

Impact of boost irradiation with surgically placed radiopaque clips on local control in breast-conserving therapy.

BACKGROUND: The purpose of this study was to determine whether boost irradiation relying on radiopaque clips placed surgically around the resected margin of breast cancer contributes to increasing the local control rate in patients with close or positive margins in breast-conserving therapy (BCT). METHODS: Among 837 patients with breast cancer who underwent BCT between November 1987 and December 1998, 181 patients with close or positive surgical margins received boost irradiation following conventional tangential whole breast irradiation. Since 1994, four radiopaque clips were surgically placed around the resected margin of the breast cancer in 155 patients treated with wide excision. The four clips were clearly and accurately identified with a CT-simulator (CT-S). The boost irradiation field was automatically determined with a safety margin of 3 cm according to one-to-one correspondence of radiopaque clips to pathologically close or positive surgical margins. In the remaining 26 patients treated before 1994, the boost irradiation field was determined according to the skin tattoo of the primary tumor. RESULTS: The median follow-up period of the 155 patients receiving the radiopaque clips was 42 months (range: 19 to 78), and that of the 26 patients without the clips was 87 months. Local recurrence was observed in two of the 155 patients who underwent boost irradiation using the radiopaque clips 39 and 54 months after the surgery, while 4 of the 26 patients developed local recurrence 14, 23, 51, and 76 months after BCT. In three of the four patients without the clips developing local recurrences, local recurrences were observed at the margin of the boost irradiation field. The 5-year local recurrence-free survival rate of patients who received boost irradiation with the radiopaque clips was 97%, and that of patients without the clips was 88%. The difference of local recurrence-free survival rates between the patients with and without the clips was significant (p<0.05). CONCLUSION: Surgically placed radiopaque clips appear to be useful for determining adequate boost field in the BCT using the CT-S and help increase the local control rate.

Adult↗

Isolation and characterization of a new immortal rat astrocyte with a high expression of NGF mRNA.

We have established a new line of immortalized rat astrocytes through transfection of plasmid pSV3-neo encoding the large T antigen of simian virus 40 into normal astrocytes. One of these immortalized astrocytes (ACT-57) with a flat and polygonal cell shape, exhibited stable growth in a chemically defined medium (modified N-2 medium) as well as in medium containing ordinary serum. ACT-57, retained a detectable level of expression of glial fibrillary acidic protein (GFAP) and its mRNA, and exhibited a stronger expression of nerve growth factor (NGF) mRNA than that of normal rat astrocytes or C6 glioma cells. NGF mRNA was significantly up-regulated by phorbol ester (12-O-tetradecanoylphorbol 13-acetate, TPA) and gamma-amino-n-butyric acid (GABA) but not by hydrocortisone. None of stimulants (TPA, dibutyryl cyclic AMP (db-cAMP), hydrocortisone, L-glutamate, carbacol, GABA, dopamine, or isoproterenol) changed the expression level of either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). There was a discrete difference between ACT-57 and normal astrocytes in the response to GABA and isoproterenol. These findings imply that normal cortical astrocytes possess a functional heterogeneity whereas the clonal astrocyte, ACT-57, does not, indicating that ACT-57 cells may be useful for in vitro studies of neuron-astrocyte interactions involving the induction of neurotrophic factors such as NGF.

Animals↗

Advanced technique for three-dimensional visualization of compound distributions in a rice kernel.

A three-dimensional (3D) visualization technique for the compound distribution in a rice kernel was developed. This technique is a combination of sectioning, staining, and digital image postprocessing. By using a special microtome system with adhesive tapes, a set of sequential sections of a rice kernel, which can be preserved with their own set of relative position data, was obtained. A single set of sequential sections was stained by various chemical techniques for the visualization of protein, starch, or lipid content. Each stained section was digitally captured using a CCD imaging device. As the stained areas represent areas containing dye-target complex, the distribution of each compound in the section was visualized in two dimensions. The digitally captured images of a single set of sequential sections were reconstructed to produce a 3D plotting image. As a result, the distributions of various compounds in a rice kernel could be visualized in a new 3D model.

Coloring Agents↗

Concurrent chemoradiotherapy for oropharyngeal carcinoma.

The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma who received definitive radiation therapy between January 1986 and June 1998 were analyzed. The median age was 61 years. All patients had squamous cell carcinoma. According to the Union International Contre le Cancer 1997 classification system, stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding the primary site, 23 tumors were in the lateral wall, whereas 2 were in the superior wall, and 3 each were in the anterior and posterior walls. The median total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment time ranged from 39 days to 113 days, with a median of 50 days. Seven patients underwent hemilateral radical neck dissection. Fourteen patients received concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times. The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%, respectively. All local recurrences occurred within 2 years. The CSS rate in patients with lateral or superior wall origin was significantly superior to that of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS rate was 83% for patients treated with concurrent chemoradiotherapy using weekly cisplatin at least 3 times, whereas that was 53% for the remaining patients (p < 0.05). No serious adverse effects were observed. It is concluded that definitive concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma appear promising.

Adult↗

Endotracheal/endobronchial metastases : clinicopathologic study with special reference to developmental modes.

BACKGROUND: Endotracheal/endobronchial metastases (EEMs) from nonpulmonary neoplasms are rare. However, their definition and developmental modes have not yet been fully elucidated. METHODS: EEMs were defined as documented nonpulmonary neoplasms metastatic to the subsegmental or more proximal central bronchus, in a bronchoscopically visible range. The clinical and pathologic features of 16 cases were reviewed, with special emphasis on the developmental modes based on five criteria: location in the tracheobronchial tree, number of lesions, laterality of lesions, depth of lesions, and relationship with the associated bronchus. RESULTS: The developmental modes were proposed on the basis of the above five criteria as follows: type I, direct metastasis to the bronchus; type II, bronchial invasion by a parenchymal lesion; type III, bronchial invasion by mediastinal or hilar lymph node metastasis; and type IV, peripheral lesions extended along the proximal bronchus. Primary tumors included colorectal in six patients, breast in three patients, uterus in two patients, osteosarcoma of the bone in two patients, and maxillary, larynx, and parotid carcinoma in one patient each, respectively. The mean recurrence interval was 65.3 months. The developmental modes were as follows: type I, five patients; type II, one patient; type III, four patients; and type IV, nine patients. Three patients underwent surgical resection. One patient has remained well for 5 years after operation. Median and mean survival times were 9 months and 15.5 months, respectively. CONCLUSION: The mean recurrence interval was long at 65.3 months, but the mean survival time was short at 15.5 months. Type I accounted for only 5 of 16 patients. Type II was found in only one patient. It is thought that this type is a rare form. Type IV affected nine patients. Treatment plans must be individualized, because in some cases, long-term survival can be expected.

Bone Neoplasms↗

Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer.

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.

Adult↗

Head-and-neck stages I and II extranodal non-Hodgkin's lymphomas: real classification and selection for treatment modality.

PURPOSE: We re-evaluated histopathological specimens of head and neck early-stage extranodal non-Hodgkin's lymphoma (NHL) using the revised European and American lymphoma (REAL) classification, and also investigated the relationship between the clinical characteristics and histopathological classification in an attempt to evaluate the usefulness of this new classification system in selecting treatment modalities. MATERIALS AND METHODS: Between 1979 and 1995, 117 patients with histologically confirmed stages I and II NHL of head-and-neck extranodal regions were treated. Of these patients, 110 specimens were available for re-evaluation. Sixty-four patients had Stage I, and 46 had Stage II diseases. All but 3 had received radiation therapy, and 59 patients were also treated with intensive combination chemotherapy. RESULTS: There were 32 extranodal marginal-zone B-cell lymphomas, 57 diffuse large B-cell lymphomas, 11 peripheral T/NK-cell lymphomas, and 10 others. The 5- and 10-year cause-specific survival rates for all patients were 72% and 62%, respectively. Patients with extranodal marginal-zone B-cell lymphoma or other low-grade B-cell lymphomas demonstrated higher survival rates than patients with other lymphomas. Patients with peripheral T/NK lymphomas showed the lowest survival rate. CONCLUSION: The REAL classification accurately indicated the prognosis of patients with NHL. These results suggest that appropriate treatment modalities can be selected using this classification.

Adolescent↗

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Journal Article↗

Cosmetic results and complications after breast conserving therapy for early breast cancer.

BACKGROUND: The cosmetic and functional results of breast conserving therapy for early breast cancer were evaluated. These are important endpoints in the assessment of breast conserving therapy in addition to tumor control and survival. The factors suspected to influence cosmesis were also analyzed. METHODS: In 206 patients with stage I and II breast cancer treated by wide excision and axillary dissection followed by radiation therapy, the cosmetic results and complications were analyzed. The cosmetic outcome was assessed by a scoring method and breast retraction assessment (BRA). As complications, arm edema and restriction of shoulder movement and late skin reactions were analyzed. RESULTS: Of the 206 patients 92% showed an excellent to good cosmetic score before radiation therapy. The score deteriorated, but gradually improved and stabilized after 1 year. Eighty-one percent of the patients had an excellent to good cosmetic score at 3 years. The BRA of the 206 patients was 1.8 cm on average before radiation therapy. It increased to 2.3 cm after termination of radiation therapy, and did not change thereafter. Tumor size over 2 cm (p = 0.005) and tumors in the inner quadrant (p = 0.003) were factors which negatively affected the cosmetic score at 3 years. Tumor size over 2 cm (p = 0.003), tumors in the upper quadrant (p = 0.005), or a nipple-tumor distance of more than 2 cm (p = 0.01) were also negative factors for the BRA at 3 years. Arm edema, restriction of shoulder movement, and late skin reaction were generally mild, and were observed in 12%, 0% and 34% of patients at 3 years, respectively. CONCLUSIONS: The overall cosmetic results of breast conserving therapy are acceptable and the complication rate is low. Tumor characteristics, tumor size, location and nipple-tumor distance are factors that affect cosmesis.

Adult↗

Determination of optimal radiation energy for different breast sizes using CT-simulator [correction of simulatior] in tangential breast irradiation.

BACKGROUND: The purpose of this study is to determine and recommend the optimal radiation source according to breast size for tangential irradiation in breast conserving therapy. METHODS: Twenty-eight patients treated at our department from January 1994 to January 1996 were studied. The dose distribution within the irradiated breast was calculated using a (60)Co-gamma ray and 6 MV-X ray. Then we compared 3-D dose distributions of the (60)Co-gamma ray and 6 MV-X ray in different-sized breasts. Three parameters (breast volume, chest wall separation, and breast height) were adopted as representative of breast size. We also examined correlations among the three parameters. RESULTS: When the breast size was large (breast volume >400 cm(3), chest wall separation > 19.5 cm, or breast height > 6.5 cm), the average volume of normal tissue which received more than 110% of the isocenter dose ("hot spot") was significantly greater with the (60)Co-gamma ray than with the 6 MV-X ray (p < 0.05). A similar result was obtained with regard to hot spots in the clinical target volume. The cold area that received less than 95% of the isocenter dose was greater using a 6 MV-X ray when the breast size was small (breast volume <200 cm(3), chest wall separation <17.5 cm, or breast height <5.0 cm). However, the difference was not significant. There was a significant correlation between breast volume and chest wall separation (r =0.849, p <0.001). Breast volume and breast height were also significantly correlated (r =0.813, p <0.001). CONCLUSIONS: Since breast volume and shape are different in each patient, the optimal energy should be selected for each case to obtain uniform dose distribution in breast-conserving therapy. Chest wall separation or breast height, which are measurable without a 3-D planning system, can substitute for breast volume as parameters for breast size. We recommend that the (60)Co-gamma ray not be used for treating large breasts, those with chest wall separation > or =19.5 cm or breast height > or =6.5 cm.

Anthropometry↗

Reproducibility of geometric distortion in magnetic resonance imaging based on phantom studies.

BACKGROUND AND PURPOSE: Image distortion is one of the major drawbacks of magnetic resonance (MR) imaging for use in radiotherapy treatment planning (RTTP). In this study, the reproducibility of MR imaging distortion was evaluated by repeated phantom measurements. MATERIALS AND METHODS: A grid-pattern acrylic phantom was scanned with a 0.2-Tesla permanent magnetic unit. We repeated a series of scans three times to evaluate the reproducibility of the distortion. In each series, co-ordinates at 432 intersections of the grid were measured for both T1- and T2-weighted spin-echo (SE) pulse sequences. Positional displacements and their variations at the intersections were calculated. RESULTS: Averages of the displacements were distributed between 1.58 and 1.74 mm, and maximum values (MAX) between 12.6 and 15.0 mm. Within 120 mm of the image center, the average values ranged from 0.73 to 0.80 mm, and from 3.4 to 5.0 mm for MAX. The absolute values of the positional variations among three series were distributed between 0.41 and 0.88 mm for average values, and between 1.4 and 4.5 mm for MAX. CONCLUSIONS: The positional variations were mostly within 3 pixels, and most of the positional displacements within the radius of 120 mm of the image center were 2 mm or less. Therefore, it will be possible to use this MR system in RTTP under limited situations, although careful applications are required for RTTP of the body. The development of a computer program to correct image distortion is expected.

Artifacts↗

Efficacy of conventional radiotherapy for recurrent meningioma.

Results of radiation therapy for 20 patients with recurrent meningioma were analyzed. The patients included 8 men and 12 women, with a median age of 55 years. All of the patients had undergone at least one operation prior to the reoperation preceding radiotherapy. Ten patients had benign meningiomas, while 4 and 6 patients had atypical and malignant meningiomas, respectively, at the time of radiotherapy. The median radiation dose was 59.4 Gy (range: 50-61.2 Gy). The local control rate at 5 years was 36% for all 20 patients (41% for benign meningiomas and 30% for atypical or malignant meningiomas). The 5-year survival rate was 47%. Excluding 2 patients whose follow-up period was shorter than the preradiotherapy interval from the previous operation, the postradiation recurrence-free period was longer than the preradiotherapy interval in 50% (9/18) of the patients. No serious complications of radiotherapy were observed. Radiotherapy seemed to be effective in controlling the tumor or delaying recurrence in at least half of the patients. However, higher doses of radiation, using sophisticated radiation techniques, may be necessary to obtain higher control rates.

Adolescent↗

Long-term results of radiation therapy for pituitary adenoma.

PURPOSE: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. CONCLUSION: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.

Adolescent↗