Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.     

In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus

We evaluated the therapeutic efficacy and neurotoxicity of adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for experimental malignant brain tumors. The 5-FC sensitivity in 9 L cells infected by an adenovirus vector expressing CD (AdexCACD) was increased 1700-fold compared with control cells. Rats bearing 9 L brain tumors were treated with an intratumoral injection of AdexCACD followed by intraperitoneal administration of 5-FC. The rats demonstrated remarkable inhibition of tumor growth by magnetic resonance imaging, and 7 of 10 rats survived for >90 days. To evaluate the potential side-effects of the 5-FC/CD gene therapy, rats were treated with an intracerebral injection of AdexCACD into the right basal ganglia and with 5-FC. The magnetic resonance imaging showed a highly enhanced area on the gadollinium-enhanced T1-weighted image at 18 days postinjection. Pathologically, this corresponded to an area of necrosis with surrounding apoptotic cells. In addition, there was demyelination and gliosis with enlargement of the lateral ventricles. These results suggest that the 5-FC/CD gene therapy may provide an anticancer effect for malignant brain tumors in humans, but also show that there are neurotoxic effects on normal brain tissue.     

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.     

A pilot study of intermittent androgen ablation in advanced prostate cancer in Japanese men

BACKGROUND: Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment. METHODS: This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached. RESULTS: Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological. CONCLUSIONS: Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.     

Three cases in which CR was obtained in residual metastatic lesions by intrahepatic arterial infusion after resection of hepatic metastases from colorectal carcinoma

We report three cases in which CR was maintained after infusion (WHF) was performed for residual metastatic lesions following resection of hepatic metastases from colorectal cancer. (Case 1) A 55-year-old female with sigmoidal cancer and hepatic metastases, H2 (4 lesions). Right lobectomy and partial resection of the left lobe were performed. On the third month following surgery, CT showed two lesions in the lateral segment of the left lobe, and WHF was then begun. One month after the start of infusion, the lesions calcified and following that, disappeared. Infusion was performed for 12 months and the total amount of 5-FU was 52.8 g. Eight years and nine months following surgery, the patient is currently alive and without recurrence. (Case 2) A 65-year-old male with rectal cancer and hepatic metastases, H3 (6 lesions). Four lesions were removed by hepatic resection; however, 2 deep lesions in S4 and S5 were left unresected. WHF was begun one month following surgery, following which the lesions were undetectable by either CT or US. Infusion was performed for 18 months and the total amount of 5-FU was 81 g. Two years and ten months after surgery an isolated lung metastasis was discovered in the right lung and a thoracoscopic partial resection was performed. Eight years and four months following the original surgery and five years and four months following the lung operation the patient is alive and without recurrence. (Case 3) A 55-year-old male with rectal cancer and subsequently discovered hepatic metastases, H3 (5 lesions). Resection of the lateral segment and a partial resection of the right lobe were performed; however, one deep lesion in S7 was left unresected. WHF was begun on the 10th day following surgery. At about eight months there was a change in shape and shrinkage of the lesion. Infusion was performed for 11 months and the total amount of 5-FU was 48 g. Ten months following surgery, CT showed a new lesion in S7 and a partial resection was performed. Intraoperative US confirmed the disappearance of the previous residual lesion in S7. One year and one month following the original surgery, the patient is alive and without recurrence. From these results, it is suggested that with postoperative WHF it is possible to obtain a complete cure in cases of colorectal cancer with hepatic metastases without the resection of all lesions. (*WHF: 5-FU 1,000 mg/m2/5 hrs/week).     

Retrospective study of the prognostic factors of remission induction for single-agent chemotherapy with cisplatin in advanced epithelial ovarian cancer

A retrospective study to explore the prognostic factor was conducted in 39 patients with advanced epithelial ovarian cancer, FIGO stage III-IV, who underwent single-agent adjuvant chemotherapy with cisplatin following primary debulking surgery. The survival rate following the adjuvant chemotherapy was 50.9% after 3 years and 44. 7% after 5 years, with a median survival time of 40.4 months. The actual dose intensity of the cisplatin ranged from 14.38 to 46.30 mg/m2/week, and the total dose/m2 was 143.79 to 645.83 mg/m2. Under these therapeutic conditions, the actual dose intensity was found to correlate with survival time (p<0.05), but there was no correlation between the total dose/m2 and survival time.     

Angiogenesis in metastatic verrucous carcinoma of the uterine cervix

A 65-year old woman operated on for verrucous carcinoma of the uterine cervix 13 years previously was found to have multiple small recurrent tumors in the retroperitoneal space. Tumor cell expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) was investigated at the second operation. Expression of VEGF was strongly positive in the tumor cells and expression of PD-ECGF was strongly positive in both the tumor cells and the interstitial cells.     

Clinical significance of mucin staining in keratinizing-type squamous cell carcinoma of the uterine cervix

Tumor tissue from 57 cases of keratinizing-type squamous cell carcinoma of the uterine cervix that had been stored in the archives of Osaka City University Hospital between May 1986 and October 1994 were stained with periodic acid-Schiff (PAS) reagent following amylase and alcian blue to identify the presence of intracellular mucin and to assess the value and significance of demonstrating the presence of mucin. Nineteen specimens (33.3%) stained positive for mucin with alcian blue or PAS following diastase. The results of mucin staining were not significant in terms of survival by Kaplan-Meier's analysis.     

Quality of life in Japanese couples during the transition to parenthood

Objective: This study aimed to examine the quality of life (QOL) in Japanese couples during the transition to parenthood with their first child.

Background: Relevant literature suggests that the health status of women drop during pregnancy and the postpartum period. However, less is known about their partner’s well-being during the transition to parenthood and little research has addressed the relationship between couples’ QOL across multiple domains.

Method: Participants included 9216 married Japanese men and women, including 3729 couples, who were expecting or raising their first child under the age of three. They independently completed questionnaires on baseline demographics and on WHOQOL-BREF.

Results: Men showed higher scores for psychological QOL, while women had higher scores for social and environment QOL. A significant interaction between gender and stage of transition to parenthood was found. The moderating effect of age between the stage and QOL was found for men on the physical and psychological domains. Couples’ QOL scores were weakly to moderately correlated.

Conclusion: Findings suggest that both men and women had lower QOL, with the exception of women’s physical QOL, after childbirth, but they showed different trends during the transition to parenthood across different domains of QOL.     

Transient phrenic nerve palsy after cardiac operation in infants.

OBJECTIVE: The aims of this study were to prove the presence of transient phrenic nerve palsy in children after cardiac surgery by successive recordings of diaphragmatic action potentials (DAPs), and to decide the indication of diaphragmatic plication in infants with postoperative phrenic nerve palsy. METHODS: The DAPs were recorded from 11 infants (age 0-54 months) under artificial ventilation after cardiac surgery. The successive DAP recordings were performed within 3-4 days (0W), 1 week (1W) and 2 weeks (2W) after operation to make a final decision for diaphragmatic plication to wean artificial ventilation. RESULTS: The patients were divided into 3 groups according to the DAP changes in successive recordings, namely, patients with normal DAPs at 0W, patients with transient depression of DAPs at 0W followed by recovery to normal DAPs by 1W and/or 2W, and patients with persistent depression of DAPs of the affected side necessitating plication of hemidiaphragm. CONCLUSIONS: In infants with phrenic nerve palsy after cardiothoracic surgery, persistently abnormal DAPs in repeated electrophysiologic examinations for at least 2 weeks after surgery are a useful guidance to support clinical and radiological evidence for an indication of diaphragmatic plication.