A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat

We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED₅₀=0.5 μM) on the respiratory rhythm was stronger than NA (ED₅₀=5 μM). The adrenaline respiratory rhythm depression was partially blocked by the α₁-antagonist prazosin or by the α₂-antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the α₁-antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or depressed (n=5 of 39) by adrenaline, and excited by α₁-agonist phenylephrine or depressed by α₂-agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA_A-antagonists bicuculline or picrotoxin, but not by the GABA_B-antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through α-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via α₁-receptors and inhibition via α₂-receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA_Aergic neurons. Received: 8 April 1997 / Accepted: 6 October 1997     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Clinicopathological features of hereditary breast cancer

The possible role of germline mutations ofBRCA1 andBRCA2 as causative agents of familial breast cancer was assessed. Their possible involvement in the carcinogenesis of hereditary breast cancer was investigated using 63 clinically suspect families. Twenty-one lineages (33.3%) had mutations in one of the twoBRCA genes. This relatively low incidence suggested that germline mutations in unknown genes are involved in the carcinogenesis of hereditary breast cancer in the Japanese population. However, the clinicopathological features characteristic of hereditary breast cancer, such as early disease onset, a high incidence of bilateral breast cancer, and a high incidence of multiple primary carcinomas in other organs were confirmed in the present study.     

Efficacy of postoperative adjuvant therapy for stage ilia breast cancer: Futraful vs futraful+tamoxifen for er-positive patients and futraful vs futraful + adriamycin for er-negative breast cancer

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located throughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage IIIa breast cancer. Patients with estrogen receptor-positive [ER( + )] breast cancer were treated with two types of regimens, ie, cyclophosphamide + adriamycin + fluorouracil (CAF; 2 cycles) + Futraful (FT) or CAF (2 cycles) + FT + tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER( + ) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation. The 5-year survival rate was 77.2% for the CAF + FT group and 74.6% for the CAF + FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF + FT + TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF + FT + TAM group was significantly higher than that for the corresponding patients in the CAF + FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF + FT+TAM group than in the CAF + FT group). Patients with estrogen receptor-negative [ER( -)] breast cancer were treated with two types of regimens, ie, CAF + FT or CAF + FT + adriamycin (ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478 (93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF + FT group and 63.0% for the CAF + FT + ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF + FT and CAF + FT + ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF + FT+ADR group than in the CAF + FT group.     

Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats

In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by perforated whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca²⁺ concentration was lowered to 0.2 mM and the Mg²⁺ concentration was increased to 5 mM. In Iow-Ca²⁺, high-Mg²⁺ solution (referred to here as low Ca), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5–12 mV in low Ca, at a rate of 12±6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonictype neurons was 2.3±1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1–1 M tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n=3) were also silent with 1 M TTX perfusion. Inspiratory neurons either became silent (n=4) or fired tonically (n=1) in low Ca. The present study by perforated whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.     

Endosalpingiosis of nonmetastatic lymph nodes along the stomach in a patient with early gastric cancer: Report of a case

We report herein the case of a 32-year-old woman who underwent distal gastrectomy with D2 lymph node dissection for gastric cancer. Microscopic examination of the resected specimen revealed signet-ring cell carcinoma of the stomach with lymph node metastases, and endosalpingiosis in the normal lymph nodes. There was no evidence of malignancy in the peritoneal cavity. To our knowledge, no other case of endosalpingiosis in the lymph nodes along the stomach has ever been reported. The possible significance of endosalpingiosis is discussed following this case report.     

RE‐EPITHELIALIZATION OF SQUAMOUS EPITHELIUM FOR A RADIATION‐INDUCED RECTAL ULCER WHILE GIVING AN ECABET SODIUM ENEMA

The present patient developed a severe rectal ulcer more than 1 month after having received external beam radiation therapy for prostate cancer. Surveillance endoscopy every 3 months demonstrated healing of this rectal ulcer using a novel therapy. He was given enemas with ecabet sodium, which provides physical protection and promotes healing by increasing prostaglandin E₂, and this process induced squamous metaplasia that halted the progression of the ulcer of radiation proctitis as a late‐phase reaction. Intrapapillary capillary loops were visualized with magnified narrow band imaging at the healing ulcer site as seen via the esophagus and, moreover, demonstrated histologically.     

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development

Background/Purpose

Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms.

Methods

Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0–III in the gallbladder and grades 0–II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens.

Results

The incidence of gallbladder carcinoma was 13/21 in grades I–II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively.

Conclusions

PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.     

An autopsy case of isolated eosinophilic coronary periarteritis: a limited form of Churg-Strauss syndrome or a new entity?

A 52-year-old man without a history of asthma or allergic diseases died of ventricular fibrillation early in the morning. His autopsy revealed no significant findings, except for a mild mural-thickening localized at the proximal region of the right coronary artery. Microscopic examination showed periarteritis with infiltration of numerous eosinophils in the adventitia. No significant vasculitis was found in any other organs. Based on the findings this seems to be the second reported case of isolated eosinophilic coronary periarteritis.