Lesion regression rate based on RECIST: prediction of treatment outcome in patients with head and neck cancer treated with chemoradiotherapy compared with FDG PET-CT

The aim of this study was to evaluate whether the lesion regression rate (ΔLR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria could be used for the prediction of treatment outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy (CRT) compared with FDG PET-CT. A total of 33 patients underwent MRI and PET-CT at pretreatment and at 8 weeks after CRT. We assessed the treatment outcome by analyzing the following parameters: the RECIST criteria, ΔLR, the European Organization for Research and Treatment of Cancer (EORTC) criteria, and pretreatment SUV_max of the primary tumor and node. The correlation between the analysis of the parameters and the results of the long-term follow-up of the patients was determined. The RECIST did not significantly correlate with locoregional control (LRC) or survival. The ΔLR was significantly lower for the lesions with locoregional failure (LRF) than for those with LRC. A threshold ΔLR of 48% revealed a sensitivity of 72.7% and specificity of 77.3% for the prediction of LRF. Progression-free survival (PFS) of patients with ΔLR ≥ 48% was significantly better than that of patients with ΔLR < 48% (P = 0.001), but not overall survival. There was a significant correlation between LRC and the EORTC (P = 0.02). The patients who achieved a complete response by the EORTC criteria showed significantly better PFS and overall survival (P = 0.01 and 0.04, respectively). The ΔLR was inferior to FDG PET-CT with respect to the prediction of patient survival; however, it may be useful for selecting patients in need of more aggressive monitoring after CRT.     

Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 ± 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 ± 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effects of salt intake on serum lipoprotein and apolipoprotein metabolism

Recently, food intake in Japan has been characterized by an increase in fat intake, especially animal-fat intake and the maintenance of excess salt (sodium chloride) intake. It is generally accepted that the increase in fat intake is closely related to atherosclerosis, and excess salt intake is a high risk factor for the development of hypertension and cerebrovascular lesions. So far, in almost all reports, the increase in fat intake and excess salt intake have been studied independently, and there have been few reports on the combined effects of these two factors. Taking the above things into consideration, it would seem to be very interesting to investigate the effect of excess salt intake on lipid metabolism. In this paper, we studied the effects of excess salt intake on lipoprotein and apolipoprotein metabolisms, using stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY) as model animals. The results obtained were as follows: A significant increase in the concentration of serum total cholesterol (TC) was observed in SHRSP and WKY, when the rats were given a regular diet (CE-2, Clea Japan Inc.) and 1% sodium chloride solution (1% NaCl) as drinking water for 4 weeks. This was accompanied by a tendency toward increases in the concentrations of serum apolipoproteins in both strains. These results suggest that excess salt intake could accelerate the production of serum total lipoproteins in SHRSP and WKY, when the rats are fed a regular diet. Next, 1% NaCl and a high-fat and high-cholesterol diet (HFC diet) were simultaneously given to SHRSP and WKY for 6 weeks. The effects of simultaneous administration on lipoprotein and apolipoprotein metabolisms were compared with those of HFC feeding. One percent NaCl did not markedly affect hypercholesterolemia in WKY, while it induced more marked hypercholesterolemia in SHRSP that was associated with extreme elevations of serum TC and the atherogenic index (A.I.). This deleterious effect of 1% NaCl in SHRSP was due to drastic elevations of cholesterol contents in the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fractions. This was also associated with marked increases in apo B contents in the VLDL, IDL and LDL fractions and significant increases in apo E contents in the VLDL and IDL fractions. These results indicate that 1% NaCl induced much larger increases in serum atherogenic beta-lipoproteins in SHRSP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal.

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.     

Dopamine agonists and valvular heart disease in Japanese patients with Parkinson's disease

Journal of Neurology - A high incidence of valvular heart disease in Parkinson's disease (PD) patients treated with ergot-derived dopamine agonists, such as cabergoline and pergolide, has been...