Risk factors for joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.

BACKGROUND: Endocrine treatment-related adverse events have a strong impact on patients' quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings. PATIENTS AND METHODS: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness). RESULTS: We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause [odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90-0.99; P = 0.02] and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06-4.95; P = 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms. CONCLUSION: Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.

Chronic liver disease increases the risk of linezolid-related thrombocytopenia in methicillin-resistant Staphylococcus aureus-infected patients after digestive surgery.

Linezolid is an effective antibiotic for treatment of infections caused by resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). However, thrombocytopenia has been reported in a certain proportion of patients receiving linezolid treatment. We investigated the risk factors for linezolid-related thrombocytopenia in MRSA-infected patients after digestive surgery. Forty-three patients who were treated with linezolid for postoperative MRSA infection were enrolled. We compared the characteristics of the patients who developed thrombocytopenia during linezolid therapy with those of the patients who did not. Thrombocytopenia was defined as a platelet ratio (post/pre-treatment with linezolid) of < 0.7. Twenty-one (48.8%) patients developed thrombocytopenia. In univariate analysis, long treatment duration, high pre-treatment levels of total-bilirubin and transaminases, and the coexistence of chronic liver disease (CLD) were found to be significant risk factors for development of thrombocytopenia. Other factors, for example pre-treatment platelet count, serum creatinine and albumin levels, and previous hepatic resection were not associated with thrombocytopenia. In the multivariate regression analysis, only CLD remained as an independent factor associated with thrombocytopenia. In addition, thrombocytopenia was more common among patients with indocyanine green retention at 15 min (ICG-R15) of more than 10% than in those with an ICG-R15 of 10% or less. Our results suggest that patients with CLD are at high risk of developing linezolid-related thrombocytopenia. Therefore, they should be targeted for more intense platelet count monitoring during linezolid therapy.

[Effective made of octreotide intravenous administration for malignant gastrointestinal obstruction in terminal cancer patients].

Continuous subcutaneous administration of octreotide acetate (SMS201-995: SMS) has not been done in Meiwa Hospital for malignant gastrointestinal obstruction in terminal patients for the following reasons: First, patients and families refuse an indwelling needle on the abdominal wall; second, an additional route limits daily activity; third, the needle site becomes inflamed or sclerosed; and fourth, an infusion pump is required. Hence, the effectiveness of three types of intravenous administration was investigated retrospectively in 15 patients in our hospital: 7 cases received intermittent IV drip infusion; 4 continuous IV drip infusion; and 4 bolus IV injection. As a result, 6 cases (86%), 2 cases (50%), and 1 case (25%), respectively, were successfully treated. These results suggested that intermittent IV administration of SMS is efficient, safe, and very convenient, while continuous IV administration is also efficient as long as the SMS potency is not reduced by mixed drugs.

Large mucinous cystic neoplasm of the pancreas associated with pregnancy.

Mucinous cystic neoplasms (MCNs) of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.

Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma.

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

Oncocytic non-functioning endocrine tumor of the pancreas.

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.