Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Appendiceal mucocele and peritoneal inclusion cyst mimicking right adnexal masses: a diagnostic challenge in gynecologic practice

Mucocele of the appendix (MA) is an uncommon disease. Preoperative differential diagnosis of MA and a peritoneal inclusion cyst (PIC) from gynecologic diseases is still a challenge. We herein report a very rare case with MA and PIC. As far as we know, this is the first report of a case having MA and PIC found simultaneously at surgery. A 31-year-old woman complained of lower abdominal pain and high fever. Based on her symptoms and laboratory tests, pelvic inflammatory disease (PID) was considered to be the most probable diagnosis. She underwent antibiotics therapy and her conditions subsided. However, ascites reappeared in a month, and ultrasound and MRI demonstrated a right ovarian cyst and a suspected right hydrosalpinx. Laparotomy revealed large PIC and MA with normal bilateral adnexa. Patients with an adnexal mass or symptoms suggesting PID should be examined carefully considering such conditions in a daily gynecologic practice.     

Spinal cord compression due to extramedullary hematopoiesis associated with polycythemia vera--case report

A 69-year-old woman with a 14-year history of polycythemia vera suffered progressive paraparesis due to epidural involvement of hematopoietic tissue. Magnetic resonance (MR) imaging demonstrated extensive epidural masses. Decompressive surgery and radiotherapy were performed and she made an almost complete clinical recovery. Serial MR imaging showed no regrowth of the other epidural masses. Extramedullary hematopoiesis occurs in patients with various hematologic disorders involving a chronic increase in the production of red blood cells, and is often associated with thalassemia, but is less common with polycythemia vera. The most frequent sites are the spleen, liver, and kidney. Extramedullary hematopoietic tissue occurring within the spinal canal and causing cord compression is very rare. Total surgical excision is not usually feasible because of the diffuse nature of extramedullary hematopoietic tissue and the possibility of recurrence, but acute neurological deterioration does require emergency surgery. Extramedullary hematopoiesis is radiosensitive and displays a rapid response to low dosages, so radiation therapy is recommended for residual tumors. Considering the possibility of central nervous system extramedullary hematopoiesis in patients with polycythemia vera, an early diagnosis is necessary for a favorable prognosis.     

Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial

BACKGROUND: The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur (UFT) for colorectal cancer. METHODS: In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes' B or C colorectal cancer, a surgery alone group (control group) and a treatment group (UFT group) to which UFT was administered at 400 mg/day for 2 years following surgery were compared. A total of 320 patients were registered between March 1991 and April 1994, and 289 of these patients were analyzed as a full-analysis set. RESULTS: The 5-year disease-free survival rate was 75.7% in the UFT group and 60.1% in the control group, respectively, and the stratified log-rank test showed the statistical significance ( P=0.0081). This difference was marked in rectal cancer ( P=0.0016) and, in particular, the local recurrence was reduced. No significant difference was observed in the 5-year survival rate. The incidence of adverse reactions on administration of UFT was low, and there was no serious adverse reaction. CONCLUSION: It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.     

Ketamine Suppresses Platelet Aggregation Possibly by Suppressed Inositol Triphosphate Formation and Subsequent Suppression of Cytosolic Calcium Increase

Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.

Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.

Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively.     

Prospective evaluation of prostate cancer detection by prostate specific antigen related parameters: comparison in serum and plasma samples.

PURPOSE: We compared the usefulness of serum and plasma samples for enhancing the specificity of prostate cancer detection. MATERIALS AND METHODS: We analyzed receiver operating characteristics curves to evaluate prospectively the cancer detection performance of prostate specific antigen (PSA) related parameters derived from serum and plasma samples in 248 and 249 consecutive patients, respectively. RESULTS: Receiver operating characteristics curve analysis showed that PSA density and transition zone PSA density were more powerful predictors of prostate cancer than total or free PSA in the group overall at intermediate serum PSA 2.1 to 10 ng./ml. and in the subgroup with total PSA 4.1 to 10 ng./ml. regardless of digital rectal examination findings. Percent free PSA performed significantly better than total PSA in patients with serum total PSA 4.1 to 10 ng./ml. PSA density, transition zone PSA density and percent free PSA did not differ substantially in patients with serum total PSA 4.1 to 10 ng./ml. However, none of these parameters distinguished patients with prostate cancer from those with benign histology when PSA was in the lower range of 2.1 to 4 ng./ml. The performance of these parameters was worse when plasma sample data were used for calculation. CONCLUSIONS: The performance of percent free PSA appears at least comparable to that of PSA density and transition zone PSA density in patients in this cohort with serum total PSA 4.1 to 10 ng./ml. without regard to digital rectal examination. The poor performance of these parameters in the lower PSA range underscores the need for other parameters to improve the specificity of cancer detection in elderly Japanese males. Continued use of serum samples is justified for measuring PSA related parameters by current assay techniques.     

Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma

The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.     

Management of enterovesical fistula in patients with Crohn's disease

PURPOSE: Enterovesical fistula in patients with Crohn's disease is intractable. Although there are some reports that the enterovesical fistula were successfully treated conservatively, closure of the fistula cannot always be achieved and surgical intervention may required for those patients. Since surgical closure of entero-entero fistula has a high risk of relapse, the strategy for treating enterovesical fistula has not been established. We evaluated the clinical findings especially in management of enterovesical fistula in Crohn's disease. PATIENTS AND METHODS: Two hundred two patients (mean age was 28.4 year old, range 12-69; 152 men and 50 women) were diagnosed as Crohn's disease during a period of 15 years between 1986 and 2000 in our institute. The incidence and the clinical results regarding the diagnosis and the treatment of enterovesical fistula in these patients were retrospectively evaluated. RESULTS: Seven in 202 patients were diagnosed to have an enterovesical fistula (3.5%, 6 men and 1 woman). The period from the initial diagnosis of Crohn's disease to the recognition of the enterovesical fistula was 11 to 204 months (mean 92.1 months). Enterovesical fistula was revealed and/or visualized by radiological enterography in 6, cystography in 2, cystoscopy in 6, and CT in 4 patients. Surgical interventions were finally conducted in all 7 patients after the failure of conservative treatment for 10 to 146 days (mean 68.2 days). Surgical procedures performed for closing the enterovesical fistula were partial cystectomy with fistulectomy in 5, fistulectomy with bladder wall overlay-suture in 2, and bladder wall overlay-suture alone in 1. No relapse of enterovesical fistula was recognized in any patient in the average observation of 41.6 months. CONCLUSION: Although the treatment of Crohn's disease has been advanced, enterovesical fistula is shown to be resistant to conservative treatment options and it makes patients in unfavorable status for relatively long duration. Our evaluation shown here demonstrated the sufficient surgical results on the closure of enterovesical fistula without any relapse, and was different from the high relapse rate after the surgical management of entero-entero fistula in similar observation period. Surgical interventions of enterovesical fistula caused by Crohn's disease might have an advantage to make diseased patients improved in shorter duration.     

Prognosis of hepatocellular carcinoma associated with Child class B and C cirrhosis in relation to treatment: a multivariate analysis of 411 patients at a single center

Background/Purpose: Given that the prognosis of patients with hepatocellular carcinoma (HCC) complicating severe cirrhosis remains uncertain, particularly with regard to various therapeutic strategies, we have evaluated the prognosis in a series of patients with homogeneous diagnostic and therapeutic histories. Methods: From 1990 to 1998, 411 consecutive HCC patients associated with Child class B and class C cirrhosis who did not have lymph node or distant metastasis were treated by partial hepatectomy (PH; n = 48), percutaneous ethanol injection (PEI; n = 105), transcatheter arterial chemoembolization (TACE; n = 189), chemotherapy, or supportive care (chemo/supportive; n = 69). Univariate survival curves were estimated. The Cox model, stratified by the treatment groups, was used for multivariate analysis. Results: As of January 1999, 305 patients (74.2%) had died. Overall median survival was 23.4 months. There were statistically significant differences between the survival times of patients receiving PH or PEI and TACE, as compared with those receiving chemo/supportive care. According to multivariate analysis, the independent predictive survival factors were: albumin level (≥3.0 g/dl), esophageal varices (i.e., absence), tumor size (≤3.0 cm), tumor number (solitary), and α-fetoprotein (AFP) level (<400 ng/ml). According to the total number of risk factors and the median survival, all patients were divided into four subgroups. For the score 0 group (no risk factor group), 3- and 5-year survival rates were 83.1% and 68.0% for PH, and 87.5% and 62.3% for PEI, respectively. In the score 1–2 group (one or two risk factors), survival rates at 3 and 5 years were 53.1% and 40.3% for PH, 54.8% and 33.2% for PEI, and 35.4% and 22.8% for TACE, respectively. For patients with a score of 3 or more, there were no differences among the treatment groups, excluding those with chemo/supportive care. Conclusions: These findings indicate that, in HCC patients with complicating Child B and C cirrhosis, PEI and PH should be considered first for subgroups of patients with scores (risk factors) of 0–2, as an acceptable survival rate was obtained in such patients. Therefore, the advantages and disadvantages of these therapies regarding tumor size and location should be counterbalanced. In patients with a score of 3 or more, TACE, when possible, could be a first choice because of its applicability and its adjuvant nature with respect to other therapies such as liver transplantation. Received: February 6, 2002 / Accepted: May 22, 2002 Offprint requests to: S. Ueno     

Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.