Masakazu Matsuda

Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma.

Objective:This prospective randomized multicenter study aims to evaluate the efficacy of extensive intraoperative peritoneal lavage followed by intraperitoneal chemotherapy (EIPL-IPC) on the overall 5-year survival of advanced gastric cancer patients with intraperitoneal free cancer cells without overt peritoneal metastasis (CY+/P−). The study also aims to determine the merit and reliability of EIPL-IPC therapy as a prophylactic strategy for peritoneal metastasis. Summary Background Data:Although the prognosis of advanced gastric cancer patients with CY+/P− is extremely poor, a suitable standard regimen for treating such patients has not yet been established. Methods:A total of 88 patients with CY+/P− from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were randomly allocated to 3 groups: surgery alone group, surgery plus intraperitoneal chemotherapy (IPC) group, and surgery plus EIPL and IPC (EIPL-IPC) group. Prognostic significance of EIPL-IPC therapy was evaluated by Kaplan-Meier curves, and its value as an independent prognostic factor was assessed by univariate and multivariate analyses. Results:The overall 5-year survival rate of the patients with EIPL-IPC was 43.8%, and this data were significantly better than that of the IPC group (4.6%, P < 0.0001) and the surgery alone group (0%, P < 0.0001). Among various recurrent patterns, the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence than both of the other groups (P < 0.0001). Univariate and multivariate analyses revealed that EIPL was the most significant impact factor. Conclusions:The present study clearly revealed that EIPL-IPC therapy significantly improved the 5-year survival span of advanced gastric cancer patients with CY+/P−. Thus, EIPL-IPC therapy is strongly recommended as a standard prophylactic strategy for peritoneal dissemination.

Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer.

PurposeVascular endothelial growth factor (VEGF) is an important factor involved in angiogenesis. Many studies have reported that the expression of VEGF in breast cancer is an unfavorable prognostic factor. However, there are few studies that have analyzed blood VEGF levels because most used serum VEGF, generally thought to originate from platelets. We measured plasma VEGF levels, which evaluate the level of tumor-derived VEGF, in various breast diseases.MethodWe analyzed 15 patients with benign breast disease, 187 patients with primary breast cancer, 32 patients with no postoperative recurrence, and 56 patients with recurrence. Plasma VEGF levels were measured by ELISA.ResultsPlasma VEGF levels were higher in malignant than in benign breast disease, and were also high in patients with recurrence or distant metastasis. In primary cases, higher VEGF levels were clearly correlated with menopause and overexpression of p53, and postmenopausal patients with high levels had a significantly lower disease-free survival rate.ConclusionThese results suggest that plasma VEGF levels in breast cancer have a clinical significance in that they are associated with the extent or metastasis of malignant lesions and are involved in angiogenesis in postmenopausal patients.

A new device for the treatment of coloproctostomic stricture after double stapling anastomoses

OBJECTIVE A new device of staple cutter was developed to evaluate the clinical effect for the treatment of rectal stricture after the double stapling anastomosis. SUMMARY BACKGROUND DATA The double stapling technique has become an established reconstruction method for patients with low anterior resection. The major complication of anastomotic stricture associated with circular stapling has been reported to be harmful and distressing. Because underlying mechanisms of stricture are not well understood, no prophylactic means have been developed and this results in postoperative dilation still being the only treatment available. Although various dilation methods are used for the treatment of stricture, none is fully satisfactory. METHODS Low anterior resection was performed in 30 patients with rectal carcinoma using a double stapling technique. First, the incidence of the anastomotic stricture and the clinical factors that contribute to the stricture formation were studied. Second, the clinical effects and advantages of the treatment of coloproctostomic stricture using the newly developed device (staple cutter) were evaluated. RESULTS Nine (30%) of 30 patients had anastomotic stricture with the symptom of distressing frequent bowel movement. There was no significant relation between the clinical factors and the stricture when compared with that of nonstricture patients. Excellent dilation was performed in all of the nine strictures using the staple cutter, and the symptom of stricture disappeared dramatically in eight patients (89%) within 1 week. The recurrence of stricture occurred in two patients; however, it has not been observed after one further use of this treatment. The staple cutter is safe and easy to use even at the bedside, and except for a conventional anoscope, no special equipment, including fluoroscope, was needed. CONCLUSIONS From the significant effects and advantages, the procedure using staple cutter is recommended highly for the treatment of circular stapling anastomotic stricture of the rectum.

An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

Carcinoma arising in fibroadenoma of the breast--a case report and review of the literature.

A 47 year old woman with two isolated lumps in her right breast underwent an excisional biopsy and the histological findings of both lesions revealed fibroadenoma with anin situ lobular carcinoma. Patey’s modified radical mastectomy was performed after which careful follow-up was continued. To date, a total 161 cases of carcinoma arising in a fibroadenoma have been reported in the world literature and a review of these literature is given following the case report.

Elevated Serum CA15-3 Levels Correlate with Positive Estrogen Receptor and Initial Favorable Outcome in Patients who Died from Recurrent Breast Cancer

BackgroundThe clinical usefulness of circulating tumor markers in breast cancer as recurrence indicators during follow-up or monitoring treatment response is still an open question. There are some patients with normal tumor marker levels who have apparent recurrence foci. In this study, we evaluated the relationships between CEA or CA15-3 levels and clinicopathological factors or outcome in patients who had died from recurrent breast cancer.MethodsTwo hundred-twenty deceased patients who had had recurrent or advanced breast cancer and who had been treated between 1986 and 2000 were enrolled in a retrospective study. Serum CEA and CA15-3 were measured regularly during the clinical course until death.ResultsThe rates of CEA and CA15-3 positivity were 41.4% and 50.9% at the time of recurrence, and rose to 67.3% and 76.8% after recurrence, respectively. The CA15-3 and CEA positivity rates significantly correlated with ER and PgR status. Serum CA15-3 status correlated significantly with survival after recurrence. Patients with CA15-3 negativity had poorer prognoses than CA15-3 positive patients. Multivariate analysis revealed that CA15-3 status was one of the significant factors for survival after recurrence.ConclusionsTumor markers, especially CA15-3, might reflect the biological characteristics of tumors such as ER or PgR status, and may be useful prognostic predictors in recurrent breast cancer. Elevated CA15-3 levels correlated with positive estrogen receptor and favorable outcome in deceased patients with recurrent breast cancer.

Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis.

Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer.

Diagnostic problems of evaluating vertebral metastasis from breast carcinoma with a higher degree of malignancy

Bone metastases from breast carcinoma are frequently observed as postoperative pathologic conditions; however, in many cases, diagnosis and treatment are difficult. Although most diagnoses of bone metastases are made by plain radiography (X‐P) or bone scintigraphy, the use of magnetic resonance imaging (MRI) has enabled detailed imaging of foci, and many more lesions have become detectable. In the current study, the authors evaluated the relation between the diagnosis of bone metastases of breast carcinoma and clinicopathologic factors, especially those of proliferative activity and effects of treatment.

Benefits of medroxyprogesterone acetate (MPA) in advanced or recurrent breast cancer with higher serum concentration

The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatogra-phy (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response (2 complete responses [CR] and 22 partial responses [PR]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of body surface (mg/cm2) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer.

An evaluation of DNA polymerase α as a prognostic predictor in early breast cancers smaller than 2 cm

We examined the relationship between proliferative activity determined by DNA polymerase α and clinicopathologic variables in breast cancer patients, and evaluated the usefulness of DNA polymerase α as a prognostic predictor in 337 early breast cancers with tumors smaller than 2 cm, which had favorable outcomes. About 60% of tumors had lower proliferative activity. A significant correlation was found between DNA polymerase α and ER, PgR, histological type, or the degree of infiltration into lymphatic vessels which reflect the prognosis. Cancers with higher DNA polymerase α activity were associated with shorter disease-free and overall survival times. In a multivariate analysis the DNA polymerase α was found to be an independent and significant factor in early breast cancer.