Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Selective ablation of porcine and rabbit liver tissue using radiofrequency: preclinical study

Temperature changes and their distribution induced by 13.56-MHz radiofrequency (RF) heating of agar phantom and porcine and rabbit liver were investigated. It was possible to produce selective local heating of approximately 50 degrees C in the RF field of 2 x 2 x 2 cm(3) of the pig or rabbit liver. Coagulation necrosis after heating became pronounced and the margin between the coagulated lesion and normal tissue became clearer with time. Within 1 week after RF heating at 50 degrees C for 20 min, the coagulated area was replaced selectively and totally by necrotic tissue.     

Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium

OBJECTIVE: The purpose of this study is to evaluate the correlation between the intranodular blood supply revealed by CT during intraarterial injection of contrast medium, mainly using helical CT, and the grade of malignancy of hepatocellular nodules associated with liver cirrhosis as classified by the International Working Party of the World Congress of Gastroenterology. SUBJECTS AND METHODS: We studied 201 histologically proven nodules (101 resected and 100 biopsied nodules), including 47 low-grade dysplastic nodules (low-DNs), 56 high-grade dysplastic nodules (high-DNs), 24 well-differentiated hepatocellular carcinomas (wd-HCCs), and 74 moderately or poorly differentiated HCCs (mp-HCCs), in 139 cirrhotic patients. Findings on CT during arterial portography (n = 201) and CT during hepatic arteriography (n = 74) were reviewed and compared with the histologic diagnosis. RESULTS: CT findings were classified into four types relative to the surrounding liver: type A (isodense), type B (slightly hypodense), type C (partially hypodense), and type D (markedly hypodense) on CT during arterial portography and type I (isodense), type II (hypodense), type III (partially hyperdense), and type IV (hyperdense) on CT during hepatic arteriography. On CT during arterial portography, the distributions of each type were low-DN (n = 47 [A, n = 36; B, n = 8; C, n = 3]), high-DN (n = 56 [A, n = 18; B, n = 20; C, n = 10; D, n = 8]), wd-HCC (n = 24; [B, n = 4; C, n = 13; D, n = 7]), and mp-HCC (n = 74 [D, n = 74]). On CT during hepatic arteriography, the distributions were low-DN (n = 26 [I, n = 18; II, n = 7; III, n = 1]), high-DN (n = 19 [I, n = 6; II, n = 7; III, n = 4; IV, n = 2]), wd-HCC (n = 15 [I, n = 1; III, n = 8; IV, n = 6]), and mp-HCC (n = 14 [IV, n = 14]). We found a statistically significant correlation between the four types and the grade of malignancy of these nodules. CONCLUSION: Findings on CT during arterial portography and CT during hepatic arteriography correlated positively with histologic grading when overlap in appearance between dysplastic nodules and HCCs occurred. The concept revealed in this study can apply to diagnoses made on the basis of Doppler sonography, dynamic CT, and MR imaging.     

Pseudolesion in segments II and III of the liver on CT during arterial portography caused by aberrant right gastric venous drainage

We report three cases of pseudolesions caused by aberrant right gastric venous drainage (AGVD) in segment II/III of the liver as demonstrated on CT during arterial portography (CTAP). On CTAP, the lesions were seen as wedge-shaped perfusion defects, and on hepatic arteriography, AGVD directed to the area with the perfusion defect was visible in all three cases. When a perfusion defect is detected at the edge of segments II/III at CTAP, a pseudolesion caused by AGVD should be suspected.     

Neurochemical evidence for inflammation-induced activation of the coeruleospinal modulation system in the rat

By using the microdialysis technique, the concentration of noradrenaline (NA) in the dorsal horn during unilateral hindpaw inflammation was compared between rats receiving bilateral lesions of the locus coeruleus (LC) and non-operated control rats. Bilateral lesions of the LC were made using an anodal current one week before testing. Unilateral hindpaw inflammation was produced by a subcutaneous injection of carrageenan (6 mg in 0.15 ml saline). Under conditions of sodium pentobarbital anesthesia, the microdialysis probe was inserted into the dorsal horn either ipsilateral or contralateral to the site of inflammation. The NA concentration in the dialysate was measured by high-performance liquid chromatography with electrochemical detection. Prior to carrageenan injection, the NA level (baseline level) did not differ between the LC-lesioned and the non-operated groups. After carrageenan injection, in the non-operated rats, the NA level increased significantly compared to the baseline level only in the dorsal horn ipsilateral to the site of inflammation, but not in the dorsal horn contralateral to the site of inflammation. An increase of the NA level was not observed in the LC-lesioned rats and in rats receiving an injection of saline. The result suggests that unilateral hindpaw inflammation produces excitation of descending NA-containing neurons from the LC, resulting in an increase of the NA level in the dorsal horn ipsilateral to the site of inflammation.     

Prevalence and symptomatology of comorbid obsessive-compulsive disorder among bulimic patients

This study sought to assess the prevalence and symptomatology of comorbid obsessive-compulsive disorder (OCD) among Japanese subjects who met the DSM-III-R criteria for bulimia nervosa (BN). The Structured Clinical Interview for DSM-III-R Patient Version was used to distinguish 26 BN patients with concurrent OCD from 52 BN patients without OCD. Obsessive-compulsive symptoms in BN subjects with concurrent OCD were evaluated using the Japanese version of the Yale-Brown Obsessive-Compulsive Scale. There were no differences in the prevalence of concurrent OCD between BN subjects with and without a lifetime history of anorexia nervosa. Among BN subjects with concurrent OCD, symptoms related to symmetry and order were most frequently identified, followed by contamination and aggressive obsessions, and checking and cleaning/washing compulsions. Bulimia nervosa subjects with concurrent OCD were more likely than subjects without OCD to have more severe mood and core eating disorder psychopathology. Comorbid OCD is a common phenomenon in Japanese bulimics (33%) similar to that suggested in BN subjects in the Western countries. Obsessive-compulsive symptoms related to symmetry and order were most frequently observed in BN subjects with concurrent OCD, which was a similar finding to that reported among restricting anorexic subjects.     

Serum C-reactive protein level and the impact of cytoreductive surgery in patients with metastatic renal cell carcinoma

PURPOSE: The prognosis of metastatic renal cell carcinoma is extremely poor. In this type of metastatic tumor cytoreductive surgery of the primary tumor is often performed to confirm the histological type or improve the response to immunotherapy with agents such as interferon or interleukin-2. However, the timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We determined the type of metastatic renal cell carcinoma for which cytoreductive surgery is beneficial. MATERIALS AND METHODS: We retrospectively reviewed the records of 58 patients in whom metastatic renal cell carcinoma was diagnosed at our hospital between 1986 and 1997. Three patients were excluded from study because they were judged to be poor candidates for surgery due to poor performance status. Of the remaining 55 patients 34 consented to cytoreductive surgery of the primary tumor and 21 did not. All except 1 patient were treated with interferon therapy. We evaluated the association of pretreatment serum C-reactive protein and the effect of surgery. RESULTS: We noted no significant difference in age at diagnosis, pretreatment serum immunosuppressive acidic protein, site of metastasis or performance status in 34 patients who underwent cytoreductive surgery and 21 who did not. Of the 21 patients in whom pretreatment serum C-reactive protein was within normal limits (less than 1.0 ng./ml.) no significant difference in disease specific survival was observed in those who did and did not undergo surgery (p = 0.4133). On the other hand, of 34 patients in whom pretreatment serum C-reactive protein was elevated (1.0 ng./ml. or greater) the prognosis was significantly better in those who did versus those who did not undergo surgery (p = 0.0054). Particularly the prognosis in patients in whom postoperative nadir C-reactive protein decreased to within normal limits was markedly better than in those in whom it remained elevated (p = 0.0025). CONCLUSIONS: Our study suggests that cytoreductive surgery is beneficial to patients in whom pretreatment serum C-reactive protein is elevated. Particularly, those in whom serum C-reactive protein decreases to within normal limits may expect longer survival when surgery is combined with postoperative immunotherapy. Currently to our knowledge the prognostic factor that predicts postoperative nadir C-reactive protein has not been identified, indicating that cytoreductive surgery of the primary tumor should be performed in patients with elevated pretreatment C-reactive protein and as performance status permits.     

Multicenter clinical trial for evaluating methylprednisolone pulse treatment of idiopathic optic neuritis in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG).

BACKGROUND: A randomized, controlled clinical trial was conducted in 1991 to compare an intravenous megadose of methylprednisolone with a control drug (mecobalamin) for treating acute idiopathic optic neuritis. CASES: Sixty-six cases from 22 clinical centers throughout Japan were examined to evaluate the treatment on visual function parameters, such as visual acuity, visual field, color vision, contrast sensitivity, and critical flicker frequency. OBSERVATIONS: The methylprednisolone pulse treatment group showed faster recovery of visual function, particularly the visual acuity at 1 week (P<.05), Humphrey field analyzer mean deviation at 3 weeks (P<.05), and color vision at 1 week (P<.05). Recovery of contrast sensitivity at several different spatial frequencies was significant in the pulse treatment group at 1 (P<.01), 2 (P<.05), and 4 weeks (P<.05) after the start of treatment. Visual function test results at 12 weeks and 1 year were essentially the same in the two treatment groups. Side effects appeared more frequently in the pulse treatment group than in the control (P<.05). CONCLUSIONS: Pulse treatment does not appear effective for idiopathic optic neuritis even though visual function in the pulse treatment group of this trial recovered more quickly during the initial phase compared to the controls. More effective and specific treatment should be established for optic neuritis.     

Phase I and pharmacologic study of oral (E)-2′-deoxy-2′-(fluoromethylene) cytidine: on a daily × 5-day schedule

(E)-2-deoxy-2-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3–4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.