Naomi Hayashi

Combination therapy with intraventricular interferon-α and ribavirin for subacute sclerosing panencephalitis and monitoring measles virus RNA by quantitative PCR assay

Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the central nervous system that leads to death within a few years. Recently, it has been reported that combination therapy with intraparenchymal interferon-alpha (INF-alpha) and intraventricular ribavirin is effective. An 11-year-old SSPE patient whose clinical symptoms progressed rapidly, was treated first with intraventricular INF-alpha and then with combined intraventricular INF-alpha and ribavirin therapy. To monitor viral load over the course of the therapy, measles virus RNA was quantified using a real-time polymerase chain reaction assay. Measles virus RNA decreased rapidly after the INF-alpha therapy was started, paralleling the decrease in the measles antibody titer in the cerebrospinal fluid and the improvement in the neurological disability. After intraventricular ribavirin was combined with INF-alpha therapy, no further improvement was observed. The neurological disability gradually progressed, although the amount of virus RNA remained low.

Low skeletal muscle density is associated with poor survival in patients who receive chemotherapy for metastatic gastric cancer

Low skeletal muscle density (SMD) and low skeletal muscle index (SMI) are associated with poor overall survival (OS) in patients with various types of cancer. We retrospectively studied SMD and SMI using computed tomographic (CT) scans in patients with gastric cancer receiving chemotherapy to evaluate its prognostic significance. SMD and SMI were obtained from CT-based analysis using Slice-O-Matic® medical imaging software in patients who received S-1 plus cisplatin chemotherapy for metastatic gastric cancer. The CT images taken within 1 month before starting chemotherapy were used. The cut-off values for determining low SMD [<33 Hounsfield units (HU) in obese and <41 HU in non-obese patients] and low SMI (<41 cm2/m2 in females, <43 cm2/m2 in non-obese males and <53 cm2/m2 in obese males) were referenced from a large population based study. The CT images of 53 patients were reviewed. The median SMD was 36.8 HU (range, 19.5-59.3 HU), and the median SMI was 39.8 cm2/m2 (range, 23.7-60.0 cm2/m2). Patients with low SMD had significantly shorter OS compared with patients having normal SMD (8.9 vs. 12.8 months, P=0.03). However, OS did not differ significantly between patients with low and normal SMI (11.1 and 14.3 months, P=0.18). Multivariate analyses confirmed that low SMD was an independent predictor of poor outcomes (P<0.01). SMD is an important prognosticator of survival in patients with metastatic gastric cancer receiving chemotherapy.

Opioid-induced constipation.

Abstract Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and bear pain instead of OIC. Laxatives have commonly been used as a prophylaxis and treatment of OIC but they are frequently ineffective because the commonly available laxatives do not target the underlying mechanism of OIC, which is the blockade of peripheral mu-receptors. Recently, there have been a number of advances in the treatment of OIC, which any physician involved with opioid-prescribing discipline should be aware of. This review will update the new options and strategies available for treating OIC along with the relevant clinical trials. Finally, this review also provides a recommendation on the preferred way to approach a patient with OIC in the modern era as well as highlight on the importance of doctor–patient communication in this setting.

Linkage of the athymic nude locus with the myeloperoxidase locus in the rat.

In rats of the BUF/Mna strain epithelial thymoma development is regulated by a single autosomal susceptible gene, Tsr‐1. In pre‐thymoma stage, BUF/Mna rats have extremely large thymuses, when compared with those of other strains of rats. The large thymus size of this strain is contributed by a thymus‐enlargement gene, Ten‐1. On the other hand, reduced thymus size and suppression of thymoma development were found in heterozygous BUF/Mna‐rnu/+ rats. Linkage studies between RNU and microsatellite and restriction fragment length polymorphism markers in ([BUFIMna‐runl rnu × WKY/NCrj]F1 × WKY/NCrj)‐ and (WKY/NCrj × [BUF/ Mna‐rnu/rnu × WKY/NCrj] F1)‐ backcross rats have led to the localization of RNU on chromosome 10. The rat homolog of mouse Mpo (myeloperoxidase) was also assigned to the chromosome 10. The gene order on the chromosome was MYHSE (myosin heavy chain of embryonic skeletal muscle) — (1.0 centimorgan [cM]) — SHBG (sex hormone‐binding globulin) — (4.0 cM) — RNU (Rowett rat nude) — (10.0cM) — MPO — (13.0 cM) — AEP (anion exchange protein). Conserved linkage of homologous loci mapped to rat chromosome 10 and mouse chromosome 11 supports the hypothesis that the RNU and MPO loci are rat homologs of the mouse nu and Mpo loci.

Impact of relative dose intensity on the outcome of metastatic colorectal cancer.

508 Background: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. There is established evidence supporting the significance of RDI in patients with various cancer, however data in patients with metastatic colorectal cancer (mCRC) are limited. In this study, we evaluate the significance of RDI of irinotecan and oxaliplatin-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into two prospective clinical trials, testing FOLFIRI (CCOG-0502) and mFOLFOX6 (CCOG-0704), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Results: The median RDI of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80% and 79%. ORRs In higher RDI (>median) group and lower RDI (

Clinical effectiveness of geriatric assessment for predicting the tolerability of outpatient chemotherapy in older adults with cancer

Oncologists have increasing opportunities to treat older adults with cancer in clinical practice. However, the tolerability of chemotherapy in older patients is not supported by adequate evidence because such patients have long been underrepresented in routine clinical trials [1]. Older patients are less likely to receive standard chemotherapy; alternative regimens supposed to be less toxic than the standard regimens tend to be selected according to the chronologic age and performance status (PS) of older patients. However, since the aging process is highly variable among individuals, chronologic age is not a sufficient biomarker for this heterogeneous population [2]. Healthcare provider-assessed PS tends to underestimate the degree of functional impairment in older patients [3]. Therefore,more reliablemethods for evaluating older adults with cancer are needed to predict the tolerability of chemotherapy. The Geriatric Assessment (GA) is a multidimensional, interdisciplinary process for evaluating the health status of older individuals. In patients with cancer, two large multicenter studies have recently shown that GA can predict grade 3 or higher toxicities due to chemotherapy [4,5]. However, since older patients are generally reluctant to compromise their quality of life only to achieve survival benefits [6], predicting only severe toxicity provides an insufficient basis for decision-making in older adults with cancer. In other words, even grade 2 or lower toxicity might result in the harmful discontinuation of successful chemotherapy. Weprospectively validatedGA for predicting the tolerability of outpatient chemotherapy in older adults with cancer (UMIN000015991).

Accessory left gastric artery aneurysms in granulomatosis with polyangiitis : a case report and literature review

ABSTRACT Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.

The impact of dose reduction and time delay in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer.

631 Background: This study was designed to evaluate the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). Methods: Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and time delay, we defined ‘dose index (DI)’ as the ratio of the actual delivered total dose to the planned total dose and ‘time index (TI)’ as the ratio of the planned duration to the actual duration of therapy. Relative dose intensity (RDI) was computed by multiplying DI by TI. DI and TI of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In patients receiving FOLFIRI ther...