Case of radiation-induced esophageal ulcer worsened after endoscopic biopsy.

Esophageal ulcer is one of the most important late complications of the esophagus treated with radiation therapy, especially with intraluminal brachytherapy. We encountered a patient with esophageal cancer treated with external radiation therapy and intraluminal brachytherapy, who developed radiation ulcer and who had severe dysphagia soon after endoscopic biopsy of the ulcer edge. A 55-year-old man was diagnosed as esophageal cancer without symptoms. He received 60 Gy/30 Fr of external radiation therapy and 12 Gy/3 Fr of intraluminal brachytherapy at a point of 5 mm in depth from the mucosa surface. He developed an asymptomatic esophageal ulcer 13 months after treatment, and endoscopic biopsy was obtained from the edge of the ulcer. Thereafter, swallowing difficulties appeared, and endoscopy revealed severe esophageal stenosis and a deep ulcer. A possibility that the biopsy contributed to worsening the ulcer can be considered. Except for cases where relapse is apparent, endoscopic biopsy is considered to be avoided.

Local radiation therapy for localized relapsed or refractory ovarian cancer patients with or without symptoms after chemotherapy.

The purpose of this paper is to prospectively evaluate the effects of local radiation therapy upon localized ovarian cancer following chemotherapy. Patients with objective relapses or refractory disease but with localized epithelial ovarian cancers and who had undergone at least one regimen of chemotherapy were enrolled in this study. External irradiation was performed on all patients. Twenty patients, with a mean age of 53.8 +/- 10.3 y, were enrolled in this study. The median number of previous chemotherapies was 2. The interval between previous chemotherapy and radiation therapy was 4.5 months. The maximum diameter of the lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3 Gy. Neither hematologic nor intestinal toxicity >grade 3 was observed. Forty-four disease sites, including the lymph nodes, vaginal cuff, pelvis, abdomen, subcutaneous regions, and the brain were irradiated. Thirty of these sites were symptom-free before irradiation. In patients with symptoms, the symptomatic relief was obtained in approximately 50% of patients. Smaller lesions (P = 0.024) and lymph nodes (P = 0.042) demonstrated better responses than larger lesions or other sites, respectively. Regression rates correlated with longer survivals (P = 0.0195) after radiation therapy. Survival was significantly better when radiation therapy was given before patients had symptoms (P = 0.001). Survival was also better in patients with lymph node disease only (P = 0.0069). We conclude that local radiation therapy may be one of the treatment options for relapsed or refractory but localized ovarian cancer, particularly when the tumor is small and/or located in the lymph nodes, even when patients had no symptoms.

Breast conservation for huge-sized locally advanced breast cancer: a case report.

A 35-year-old woman with locally advanced stage IIIB breast cancer (medullary carcinoma) 12 cm in diameter underwent neoadjuvant chemotherapy consisting of three courses of intraarterial infusion [adriamycin (ADR), mitomycin (MMC), cisplatin (CDDP), 5-fluorouracil (5FU)] and four cycles of systemic chemotherapy (ADR, epirubicin, cyclophosphamide, MMC, CDDP) for three months. The tumor markedly diminished after the first course of intraarterial infusion chemotherapy, with a 3-cm tumor remaining after the completion of preoperative administration. Pathologically complete response was noted in specimens resected following breast conservation surgery. Postoperative radiotherapy was added and adjuvant chemohormonal therapy was continued for two years. The patient is alive without recurrence and has been able to conserve the breast for the past eight years, neoadjuvant chemotherapy including intraarterial infusion enabled breast conservation treatment even for huge-sized locally advanced breast cancer.

Florid endocervical glandular hyperplasia with pyloric gland metaplasia: a radiologic pitfall.

A case of florid endocervical glandular hyperplasia with pyloric gland metaplasia is described. MR images showed multiple and conjugated cysts in the uterine cervix, which suggested adenoma malignum. A postoperative examination revealed florid but definitely benign endocervical glandular hyperplasia. Hitherto described radiologic features considered suggestive of adenoma malignum are not necessarily specific and can be a diagnostic pitfall.

Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma.

OBJECTIVE: We attempted to prospectively determine the role of magnetic resonance imaging (MRI) in very early cervical cancer. STUDY DESIGN: T2-weighted and T1-dynamic enhanced images from patients with invasive or noninvasive lesions of the cervix were reviewed by two radiologists who had no clinical information on these patients. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. RESULTS: Seventy-nine cases were entered into the study and 75 were evaluable. Accuracy of T2 MR images for invasive and noninvasive disease by Radiologist 1 and Radiologist 2 was 0.8533 and 0.7733, respectively. Accuracy was greater (0.9867 and 0.9467, respectively) for the detection of noninvasive plus microinvasive lesions 5 mm. Dynamic technique provided only limited additional value in the detection of microinvasive cervical carcinoma. CONCLUSION: Simple T2 MRI is useful in differentiating noninvasive or microinvasive cervical lesions from invasive cervical carcinoma of the cervix >5 mm.

Expression of cell cycle regulator genes in KB, a human squamous cell carcinoma cell line, after irradiation.

DNA damage induced by irradiation causes overexpression of the p53 gene, and subsequently the upregulation of p53 downstream genes involved in cell cycle modification. Irradiated malignant cells which possess wild-type p53 have been known to undergo G1 arrest due to p21/Cip1/Waf1 upregulation. Other p53 downstream genes related to the modification of the cell cycle such as gadd45 may cause G2 arrest. Many of the genes which regulate the cell cycle progression have been identified, including the G1 phase specific ink4 family of cyclin-dependent kinase inhibitors (CDK-I), another group of CDK-Is, which affect the cyclin-CDK complexes ubiquitously, and S/G2 accelerator genes. The sequential changes in these cell cycle regulator genes after irradiation has not been clarified. We analyzed the appearance of the apoptotic fraction and cell cycle perturbation after irradiation using KB, a human squamous cell carcinoma line derived from oral floor, and examined the alteration of gene expression for cell cycle regulator genes. The KB cells proceeded to undergo apoptosis in a time and dose dependent manner after irradiation and showed G2 arrest accompanied by upregulation of p53, ubiquitous CDK-Is, and S and G2 accelerator genes.

Interstitial brachytherapy for recurrent breast cancer using a high dose rate Ir-192 remote afterloading system: a report of two cases.

We employed interstitial brachytherapy using a high dose rate Ir-192 remote afterloading unit in two breast cancer patients with locoregional recurrence. In the first case, skin metastasis was treated, with favorable control of the infield tumor but subsequent persistent sequelae and multiple outfield metastases. This experience caused us to be cautious when choosing brachytherapy for the second case, in whom a solitary metastasis to an axillary lymph node was successfully treated. Although this method is still investigational, it may play a critical role in the treatment of locoregional recurrence resistant to other treatment modalities.

Role of magnetic resonance imaging (MRI) in early cervical cancer.

The aim of this study was to prospectively determine if invasive carcinoma of the cervix can be ruled out by negative magnetic resonance image (MRI) findings. Eligible patients were those who were scheduled to undergo either hysterectomy or conization because of invasive or non-invasive lesions of the cervix. T2-weighted and T1-dynamic enhancement images were reviewed by two radiologists who had no information on these patients except for the preoperative diagnosis. Clinical information regarding location of the disease was not given. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist who was not provided with MRI information. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and 0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647, respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist 1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and specificities were calculated for prediction of non-invasive plus microinvasive lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The dynamic technique provided only limited additional value in the detection of early invasive cervical carcinoma.

The efficacy of conventional radiation therapy in the management of pituitary adenoma.

PURPOSE: To evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas. METHODS AND MATERIALS: We reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1-14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed. RESULTS: Mass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushing's disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushing's disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation. CONCLUSION: We conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.

[A case of clear cell carcinoma of the ovary responding to a paclitaxel-carboplatin combination chemotherapy].

Clear cell carcinoma of the ovary is believed to be chemoresistant; therefore, choosing anticancer agents is often difficult. In this report we present a case of ovarian clear cell carcinoma that showed a significant response to a combination chemotherapy with paclitaxel and carboplatin. The patient is a 51-year-old Japanese female with a history of Gn-RH treatment for endometriosis that was terminated three years before the presentation of this disease. She was referred to our hospital because of a huge abdominal mass. The initial surgery revealed the tumor was a clear cell carcinoma of the left ovary, showing a predominantly solid growth pattern as well as papillary and tubular patterns. Both architectural and nuclear grades were interpreted as 3, and mitotic count was up to 5/10 high-power fields. Therefore, the tumor was considered to be grade 2. A huge para-aortic lymph node metastasis was not resectable. Combination chemotherapy using paclitaxel at 175 mg/m2 in 3 hr intravenous infusion followed by intraperitoneal infusion of carboplatin at AUC of 7.5 as a bolus was administered. The regression rate of the para-aortic lymph node metastasis was 85%, lasting more than 5 months. We believe that the combination of paclitaxel and carboplatin is one treatment choice for clear cell carcinoma of the ovary.

High dose rate microselectron mould ratiotherapy of a widespread superficial oral cancer.

Treatment of a case of widespread superficial oral squamous cell carcinoma with external beam irradiation, followed by high dose rate Microselectron mould radiotherapy, is reported. The tumor disappeared macroscopically after treatment, but there was infield recurrence in the buccogingival sulcus where the radiation dose might have been inadequate. Apart from some radiation mucositis within the treated area, edema and a superficial ulcer were observed in the tongue. These were considered to be due to radiation overdose. Although there is room for improvement, this mode of treatment has something to offer patients with hard-to-cure cancer.

[Optimal thoracic irradiation for stage IV lung cancer].

To investigate optimal thoracic irradiation (TI) for stage IV lung cancer, we retrospectively reviewed 150 patients. In all, 101 patients underwent radiotherapy for the primary lesion, and 130 had radiotherapy for metastasized sites. TI fields were basically divided into two groups; whole thoracic lesion irradiation (WTLI) and partial thoracic lesion irradiation (PTLI). Overall survival rates at 6 months, 1 year and 2 years were 58%, 27% and 11%, respectively, and MST was 7.1 months. There was no difference in survival according to histological type. On univariate analysis, the factors of good prognosis included good PS, free of bone metastasis, metastasis limited to a single organ, TI, chemotherapy, age (less than or equal to 75 years), and TN factors (T0-2 and N0-1). Multivariate analysis showed PS was the predominant factor. Among the patients treated with TI, survival rates of patients with PS 0-1 were superior to those of patients with PS 2-4. Radiation pneumonitis was more frequent in WTLI than in PTLI. The rates of thoracic failure death were 31.7% in patients treated with TI and 63.3% without TI. However, the size of the thoracic radiation field did not affect the rates of thoracic failure death. We concluded that TI for stage IV patients could reduce thoracic symptoms and increase the survival rate in the subgroup with good PS. Furthermore, we considered PTLI was worth while in the subgroup with poor PS.

[Clinical results and prognostic factors of radiotherapy for bone metastases from breast cancer].

The purpose of this study was to analyze the results of initial radiotherapy for bone metastases (BM) from breast cancer and to investigate the prognostic factors. Between 1981 and 1995, 65 women (109 lesions) received initial radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG score. The control rates of pain including the prevention of pathological fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median survival time of all patients was 11 months, and the survival rates were 56% at 1 year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long-term survivors. Univariate analysis showed that a normal state of LDH, no other metastatic organs, a disease-free interval longer than two years, good performance status (0 or 1), BM limited to the axial bones, maintenance chemo-hormonal therapy and an age of more than 55 years were good prognostic factors. Multivariate analysis showed that LDH, age and performance status were significant predictors of prognosis. It is important to note the prognostic factors at the initial treatment of BM from breast cancer. We consider that further prospective studies are needed to determine the optimal treatment schedule, including radiotherapy and its combination with chemohormonal therapy, for BM.

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma.

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

[A case of local advanced cervical esophageal cancer treated with concurrent radiochemotherapy followed by surgery].

A 61-year-old-male with local advanced inoperable cervical esophageal cancer (squamous cell carcinoma, T4N1M0 stage III) was treated by concurrent radiochemotherapy. A dose of 50.6 Gy/46 Fr/36 days and one course each of CDDP-5-FU and nedaplatin-5-FU were delivered safely. Radical surgery could be performed thereafter because of the good tumor response. Pathological CR was obtained in metastatic cervical lymph nodes and almost total necrosis in primary cancer. Concurrent radiochemotherapy produced a significant improvement in this case of advanced cervical esophageal cancer.

[Experience in treatment of patients with locally advanced or recurrent breast cancer: intraarterial infusion chemotherapy combined with radiotherapy].

For the purpose of local control and breast conservation, intraarterial infusion chemotherapy combined with radiotherapy has been indicated in patients with locally advanced breast cancer both in primary and recurrent cases. The present series, evaluated during the past 4 years, consisted of 15 patients 35-83 years of age, with invasive ductal carcinoma, including 10 with primary breast cancer (stage IIIb: 1; IV: 9) and 5 with postoperative recurrence (stage IIIb: 2, IV: 3). Intraarterial chemotherapy is started, basically infusing ADM 50 mg, MMC 10 mg and CDDP 50 mg into the internal thoracic and/or subclavian artery 1-3 times, followed by reduction surgery (quadrantectomy: 4, wide resection: 2) and radiotherapy to the breast, supraclavicular, parasternal and cervical regions according to tumor extent. Local response after arterial infusion was CR: 2, PR: 10, NC: 3 (response rate: 73%). The response rate of distant metastases after arterial infusion was 73%. Of 10 patients with primary breast cancer, recurrence was noted in 1. Breast conservation was successful in 8 of 10 patients. One of them, in stage IIIb, has survived for 4.5 years with no evidence of disease and with breast conservation. Five patients with postoperative recurrence showed CR with no recurrence after intraarterial chemotherapy and radiotherapy. Acute skin reaction occurred in 6 patients, and was especially frequent in patients with postoperative recurrence (4 of 5). According to these results, combined therapy affords breast conservation even in patients with locally advanced breast cancer, and improves patient's QOL in stage IV.