Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock.

PURPOSE: We evaluated the relations among the arterial carbon monoxide (CO) concentration, heme oxygenase (HO)-1 expression by monocytes, oxidative stress, plasma levels of cytokines and bilirubin, and the outcome of patients with severe sepsis or septic shock. METHODS: Thirty-six patients who fulfilled the criteria for severe sepsis or septic shock and 21 other patients without sepsis during their stay in the intensive care unit were studied. HO-1 protein expression by monocytes, arterial CO, oxidative stress, bilirubin, and cytokines were measured. RESULTS: Arterial blood CO, cytokine, and bilirubin levels, and monocyte HO-1 protein expression were higher in patients with severe sepsis/septic shock than in non-septic patients. Increased HO-1 expression was related to the arterial CO concentration and oxidative stress. There was a positive correlation between survival and increased HO-1 protein expression or a higher CO level. CONCLUSIONS: Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.

Long-term results and management of ureteral transitional cell carcinoma using the holmium: YAG laser via rigid-ureteroscopy.

The standard operative procedure for ureteral transitional cell carcinoma is nephrouterectomy with partial cystectomy at the affected ureteral orifice. However, nephron-sparing surgery and endoscopic surgery and management have become common practice for low-grade and low-stage cases. We investigated the follow-up results of patients who underwent endoscopic surgery using the holmium:YAG laser, and evaluated its treatment effect. The patients were 4 men and 3 women aged from 68 to 87 years (mean: 74.7 years). Two were imperative cases and 5 were elective cases. The tumor size ranged from 8 to 25 mm (mean: 15.4 mm). Hydronephrosis was not found in any case, and urinary cytology was negative in all cases. Biopsy revealed 5 cases of grade 1, and 2 of grade 2. A Versa Pulse Select 80 laser generator, a 365-microm slim line laser fiber, and a rigid ureteroscope with 8F-point diameter were used. A 6F double J catheter was placed postoperatively for 3 weeks. Pulse energy was set at 0.5-1.0 J (mean: 0.8 J) with a frequency of 10 Hz. The total amount of energy was 0.9-11.22 KJ (mean: 2.89 KJ) and the operation time including ureteral stent placement was 20-97 min (mean: 66 min). Neither urinary tract perforation nor ureteral stricture associated with laser irradiation was observed. The postoperative follow-up period ranged from 23-88 months (mean: 67.8 months). Patients underwent urinary cytological examination once a month, and cystoscopy, retrograde pyelography and urethroscopy once every 3 months for 2 years, then once every 6 months thereafter. One patient developed tumor recurrence 23 months after surgery and received another laser treatment, but no recurrence has been observed in the other 6 patients (85.7%). Transurethral endoscopic surgery and management using the holmium:YAG laser is safe and effective nephron-sparing surgery for ureteral transitional cell carcinoma, and good long-term treatment results can be expected even in elective cases if the indications are carefully selected.

Cyclooxygenase-2 expression in invasive transitional cell carcinoma of the urinary bladder.

Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.

Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis.

We analyzed clinical data to identify prognostic indicators in prostate cancer patients with bone metastasis. The subjects were 60 patients with bone metastasis out of 165 patients diagnosed with prostate cancer at our clinic over 6 years from January 1998 to December 2003. The age at the initial diagnosis was 61 to 91 (mean: 73.7 +/- 7.5) years old. The following items were considered to be possible prognostic indicators: T (type) classification, N (node) classification, Gleason score, prostate specific antigen (PSA) value before therapy, disease grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum calcium (Ca), hemoglobin (Hgb), and platelet count (Plt). The 5-year overall survival rate was 45.7% in the 60 patients. Univariate analysis showed statistically significant differences in N (1), Gleason score 7 + 8/Gleason score 9 + 10, and LDH level (p = 0.0053, 0.0261, and 0.0049, respectively). Multivariate Cox proportional hazard analysis of these three items showed a statistically significant difference in LDH level and Gleason score 9 +/- 10 (p = 0.0167 and 0.0371). LDH was suggested to be an excellent prognostic indicator, because of its objectivity and convenience of measurement, in prostate cancer patients with bone metastasis.

Potential for molecular-targeted therapy targeting human epidermal growth factor receptor-2 for invasive bladder cancer.

Expression of human epidermal growth factor receptor-2 (HER-2/neu or HER-2) oncoprotein in invasive bladder cancer was examined by immunohistochemical staining in order to evaluate the potential for molecular-targeted therapy targeting HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients who were examined at Aichi Medical University Hospital and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). Immunohistochemical staining using a Hercep test kit was performed to detect HER-2 expression, which was classified into four levels from 0 to 3+ by two experienced pathologists, with 2+ and 3+ determined as positive. HER-2 staining in the primary tumor was determined as 0 in 9 (22.5%) patients, 1+ in 14 (35%), 2+ in 10 (25%), and 3+ in 7 (17.5%), resulting in 17 (17/40, 42.5%) HER-2-positive patients. According to the classification of grade, one (1/3, 33.3%) grade 2 patient and 16 (16/37, 43.2%) grade 3 patients were HER-2 positive (p=0.99). According to the classification of stage, 12 (12/22, 54.5%) pT2 patients, 2 (2/13, 15.3%) pT3 patients, and 3 (3/5, 60%) pT4 patients were HER-2 positive (p=0.05). Lymph node metastasis was found in 10 patients, and 3 (3/6, 50%) pN2 patients were HER-2 positive (p=0.32). There was a statistically significant difference between patients with HER-2-positive primary tumors and those with HER-2-positive metastatic lymph nodes (p=0.02). This study suggested that 42.5% of patients with invasive bladder cancer may benefit from molecular-targeted therapy targeting HER-2, and that the efficacy of molecular-targeted therapy can be expected even for patients with lymph node metastases as long as their primary tumors are HER-2 positive.

Transvascular fluid distribution of hyperoncotic Dextran solution.

PURPOSE: The purpose of this study was to confirm the changes in extra-aand intravascular fluid distribution during an i.v. influsion of hyperoncotic Dextran solution. METHODS: Twenty-three mongrel dogs with normal capillary integrities were divided into four groups. The R1 and R2 groups received i.v. infusion of Ringer lactate (RL) with a rate of 10 and 30 ml·kg-1·h-1, the D group 6% Dextran 70 solution (DEX) of 10 ml·kg-1·h-1. and the RD group DEX of 10 plus RL of 20 ml·kg-1·h-1. The distribution of infused fluid was assessed with the changes in circulating blood volume (CBV), extravascular fluid volume (EVW), and thoracic duct lymph volume (QL). RESULTS: In the R1 and R2 groups, EVW increased by 63% and 51%, respectively, of total infusion volume (tInf), while CBV increased by only 10% and 13% of tnf. In the D and RD groups, CBV increased by 103% and 51% of tInf. However, EVW decreased by 21% and increased by 32% of tInf, respectively. In the latter groups, the plasma volume filtered out into the extravascular compartment was less than in the corresponding former group by 52% and 6% of tInf, respectively and the restoration ratio of EVW by lymph was about 3 to 1.8 times greater. CONCLUSION: One-fourth to one-third of the plasma expanding effect of 6% Dextran 70 solution was ascribed to direct fluid drawing from the extravascular space, and the rest was due to both the decrease in plasma filtration into extravascular space and the increase in lymphatic restoration of EVW.