Kunimitsu Kawahara

Down-regulation of drs mRNA in human colon adenocarcinomas

We have previously reported that the drs gene, whose mRNA expression is down‐regulated by retroviral oncogenes such as v‐src and v‐K‐ras, has the ability to suppress transformation by v‐src and v‐K‐ras in the rat cell line F2408. We have also isolated a human homolog of this gene (h‐drs) and shown that expression of h‐drs mRNA is markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down‐regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down‐regulation of the drs gene and malignant tumor formation in human cancer tissues, we examined expression of drs mRNA in human normal tissues, colon adenoma, and adenocarcinoma tissues by in situ hybridization. Expression of drs mRNA was detected in most normal tissues tested, including those of the colon, bladder, and ovary. However, drs mRNA was hardly expressed in any of the colon adenocarcinoma tissues examined. Northern blot analyses confirmed these results. Neither gross deletion nor re‐arrangement of the drs genome was detected by Southern blot hybridization in these adenocarcinoma tissues. drs mRNA was significantly expressed in colon adenoma with mild atypia but down‐regulated in adenomas with moderate atypia and focal carcinoma. Our results indicate that down‐regulation of drs mRNA is closely correlated with development of colon adenocarcinoma, suggesting a tumor‐suppressor function of the drs gene in human cancers. Int. J. Cancer 87:5–11, 2000.

Hyperfunctioning intrathyroid parathyroid adenoma: Report of two cases

We report herein two cases of intrathyroid parathyroid adenoma, which is a rare condition in patients with hyperparathyroidism. In the first patient, an excised intrathyroid nodule was diagnosed to be parathyroid adenoma postoperatively. In the second patient, preoperative localization studies suggested the possibility of an intrathyroid adenoma. When a pathological gland is not found during surgery for primary hyperparathyroidism, an ectopic parathyroid gland including an intrathyroid adenoma should thus be considered.

Gastrointestinal stromal tumor of the rectum with activating mutation of c-kit

Nonepithelial malignancies of the large bowel are rare. A new disease entity, gastrointestinal stromal tumors, has attracted attention among primary mesenchymal tumors of the gastrointestinal tract. Here we present a case of spindle-cell sarcoma of the rectum, lacking either smooth muscle cells or neural elements. Immunohistochemical findings and sequencing of the c-kit proto-oncogene diagnosed this tumor as a malignant gastrointestinal stromal tumor of the rectum.

A Retrospective Study of Breast Cancer Patients Treated with Quadrantectomy without Radiation Therapy.

BackgroundRadiation therapy after breast-conserving surgery (BCS) reduces the risk of local recurrence. However, whether radiation therapy is necessary for all patients undergoing BCS remains unclear.MethodsIn order to determine the selection criteria for patients who can safely omit radiation therapy and to confirm the survival benefit of quadrantectomy without radiation therapy, we reviewed 107 patients who underwent quadrantectomy without radiation therapy between February 1988 and July 1995.ResultsThe 5-year overall survival, disease-free survival and cumulative local recurrence rates were 93.7%, 80.7% and 12.1% respectively. There were no significant differences of 5-year overall survival (94.0% vs 94.1%) and disease-free survival rates (83.1% vs 70.0%) between patients with or without tamoxifen. The 5-year cumulative local recurrence rate of patients with tamoxifen, however, tended to be lower (p=0.0810) than that of patients without tamoxifen. The 5-year cumulative local recurrence rate of the patients aged 45 or less was significantly higher than that of patients aged from 45 to 55 years and those over 55 (p=0.0090 and 0.0089, respectively). In ER positive patients, the 5-year cumulative local recurrence rate of patients with tamoxifen tended to be lower (p=0.0791) than that of patients without tamoxifen.ConclusionThe survival rate of quadrantectomy without radiation therapy was acceptable. While the risk of local recurrence following quadrantectomy without radiation therapy is substantial, radiation therapy following quadrantectomy might not be necessary in elderly ER positive women receiving adjuvant tamoxifen therapy.

Correlation between clinical features and prognosis of local recurrence after breast-conserving therapy.

AbstractBackground. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled.nMethods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients.nResults. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy.nConclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery.

Risk factors for local recurrence after breast-conserving therapy

AbstractBackground. Breast-conserving therapy has been widely accepted as a standard treatment for early breast cancer both in Western countries and in Japan. In Western countries, many studies have investigated the risk factors for local recurrence after breast-conserving therapy (BCT), but few such studies have been done in Japan.nMethods. To determine the risk factors for local recurrence in 399 breast cancer patients (stage I and II, n = 396; stage III, n = 3) who had undergone BCT with or without postoperative radiation therapy, we evaluated their clinicopathological features by univariate and multivariate analyses. The patients were treated at Osaka National Hospital between February 1988 and December 1997.nResults. Univariate analysis showed that a young age (≤45 years; P = 0.0005) was a significant risk factor for local recurrence, while radiation therapy (P = 0.0058) and adjuvant endocrine therapy (P = 0.0041) significantly reduced the risk of local recurrence. In patients with BCT, without radiation therapy a positive surgical margin significantly increased the risk of local recurrence (P = 0.0470). Multivariate analysis showed that a young age (P = 0.0285) was a significant independent risk factor for local recurrence, while radiation therapy (P = 0.0457) significantly decreased recurrence. In patients with a negative surgical margin, radiation therapy (P = 0.0158) and adjuvant endocrine therapy (P = 0.0421) significantly reduced the relative risk of local recurrence, to 0.160 and 0.366, respectively. In patients with a positive surgical margin, radiation therapy marginally significantly (P = 0.0756) reduced the relative risk of local recurrence, to 0.181, and adjuvant endocrine therapy significantly (P = 0.0119) reduced the risk, to 0.076.nConclusions. Young age and lack of radiation therapy or adjuvant endocrine therapy were risk factors for local recurrence in breast cancer patients treated with breast-conserving therapy, with surgical margin status also being a possible risk factor.