Effects of the COX-2 inhibitor FK3311 on ischemia - reperfusion injury in the rat lung.

Ischemia-reperfusion injury is induced by activation of the arachidonic acid cascade following the induction of cyclooxygenase-2. This study evaluated the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury in the lung. Male Wistar rats were divided into two groups. In the FK3311 group (n = 27), FK3311 (4 mg/kg) was administered intravenously 5 min before ischemia, while in the control group (n = 27) only vehicle was injected. Warm ischemia was induced for 1 h by clamping the left hilus. The arterial oxygen pressure (PaO(2)) and saturation (SaO(2)) were measured 30 and 120 min after reperfusion. Serum thromboxane B(2) and 6-keto-prostaglandin F(1alpha) were also measured 30 min after reperfusion. Lung specimens were harvested 120 min after reperfusion for histologic examination and polymorphonuclear counts, and immunostained with cyclooxygenase-2. The 1-week survival rate in the two groups was compared. PaO(2) and SaO(2) 30 and 120 min after reperfusion were significantly (p < .05) better in the FK3311 group. Serum thromboxane B(2) levels were significantly (p < .05) lower in the FK3311 group. However, there was no significant difference in 6-keto-prostaglandin F(1alpha). Histologically, tissue damage was mild and polymorphonuclear infiltration was reduced in the FK3311 group compared to the control group. The expression of cyclooxygenase-2 in the alveolar epithelium based on immunostaining was suppressed in the FK3311 group. The 1-week survival rate was significantly (p < .05) higher in the FK3311 group. We conclude that FK3311 has protective effects on pulmonary ischemia-reperfusion injury, and results in improvement in the 1-week survival rate.

The comparison of mitogen-activated protein kinases that become activated within the left ventricular and right atrial tissues following heart transplantation in canine model.

The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in ischemia/reperfusion injury. Some reports have documented MAPKs activation of the myocardium in human models, using right atrial (RA) tissue for samples. This study compared the activation of MAPKs in left ventricle (LV) and RA tissues in canine heart transplantation. Four dogs were used as baseline data at two points, before and 20 min after warm ischemia (baseline model), and eight dogs (four pairs of donor and recipient) were used at other points: 4 h after cold ischemia, and at 10, 60, and 180 min after reperfusion (transplantation model). In the transplantation model, donor hearts were left in situ for 20 min after cardiac arrest, and were immersed in Celsior solution for 4 h after coronary flushing. Orthotopic heart transplantation was then performed. Two groups were created: the LV and RA groups (n = 4 in each group). Heart tissue was harvested from the left ventricular wall in the LV group and from the right atrial appendage in the RA group. The activation of MAPKs, including p38 MAPK, c-Jun N-terminal protein kinase (JNK), and extracellular signal-regulated protein kinase (ERK), was evaluated at each point. The activation patterns of p38 MAPK and ERK were similar in the RA and LV groups, but JNK activation was different in the two groups, after ischemia and reperfusion. Thus, RA tissue may be deliberately used as a substitute for LV tissue when investigating the activation of MAPKs in a human model.

The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat.

BACKGROUND/AIMS: This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver. METHODOLOGY: Male Sprague-Dawley rats were used in this experimental study. Total hepatic ischemia was induced with a clamping portal triad. The animals were divided into two groups: the control group and the FK group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after reperfusion. The liver tissues obtained from animals at 2h after reperfusion were excised for histopathology. RESULTS: The serum levels of AST, ALT, and LDH were significantly lower in the FK group than in the control group. Similarly, in the FK group, the serum levels of TxB2 were significantly lower than in the control group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The liver tissue blood flow at 120 min after reperfusion was significantly higher in the FK group than in the control group. The histopathological study showed that hepatic tissue damage was milder in the FK group than in the control group. CONCLUSIONS: FK has protective effects on hepatic ischemia-reperfusion injury stemming from the marked inhibition of TxA2.

Mass screening of multiple abdominal solid organs using mobile helical computed tomography scanner--a preliminary report.

OBJECTIVE: The possibility of a new screening procedure for multiple abdominal solid organs using a mobile helical computed tomography (CT) scanner was evaluated. METHODS: A total of 4,543 residents, who were 40 years of age or older, received CT scanning without contrast medium. The mean age of participants was 64 years including 2,022 males and 2,521 females. RESULTS: A total of 2,105 abnormal findings were uniquely detected in 1,594 participants. Liver and kidney diseases including ureter occupied around 30% of total abnormal findings, respectively. Besides frequent cystic or calcified lesions, solid tumours were suspected in 56 lesions, which received further examination by specialized physicians. Five (9%) of them were confirmed as being malignant tumours including pancreatic cancer in two patients, and liver, lung and ovary cancers in one patient each, respectively. All five patients with each malignant lesion received curative operations. Small-sized abdominal aortic aneurysms and heart valve diseases were uniquely found in 22 and two patients, respectively. CONCLUSION: Qualitative diagnoses of solid tumours were difficult using CT findings without contrast medium. CT screening procedures require further investigation in aspect of the selection of examinees, CT scanning procedure, sensitivity and specificity, and cost-effectiveness.

KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts.

BACKGROUND: A novel immunomodulator, KRP-203, the molecular structure of which has some similarity to FTY720, has been developed for use in organ transplantation. The present study was designed to investigate the potency and safety of KRP-203 on allograft survival against both acute and chronic rejection in rat skin and heart transplantation. METHODS AND RESULTS: KRP-203 significantly prolonged skin or heart allograft survival of a minor histocompatibility complex (mHC)-disparate (LEW to F344) rat combination. Histopathological and immunohistochemical analysis at 100 days after mHC-disparate rat heart transplantation revealed that KRP-203 treatment significantly inhibited infiltration of inflammatory cells, including macrophages and T cells; expression of endothelin-1 and transforming growth factor-beta1; and IgG deposition and eventually attenuated neointimal formation and myocardial fibrosis. KRP-203 also prolonged heart allograft survival in a major histocompatibility complex (MHC)-incompatible (DA to LEW) rat combination, but the efficacy was not as significant. However, KRP-203 combined with a subtherapeutic dose of cyclosporin A synergistically prolonged the heart allograft survival. Flow cytometric analysis demonstrated that KRP-203 reduced the number of peripheral blood mononuclear cells (lymphocytes and monocytes) but not granulocytes and enhanced lymphocyte homing into peripheral lymph nodes. The influence of KRP-203 on heart rate changes in Hartley guinea pigs was examined. KRP-203 had less of a tendency to cause bradycardia than FTY720. CONCLUSIONS: These findings demonstrated that KRP-203 prolonged skin and heart allograft survival and significantly attenuated chronic rejection and bradycardia as an adverse effect. Therefore, KRP-203 offers considerable potential as a novel therapeutic immunosuppressant in patients with organ transplantation.

The regulatory effect of tamoxifen on fibronectin expression in estrogen-dependent MCF-7 breast carcinoma cells.

We investigated the regulatory effect of tamoxifen (TAM) on fibronectin (FN) expression in estrogen-dependent MCF-7 breast carcinoma cells both in vitro and in vivo. in vitro, MCF-7 cells were cultured with 17beta-estradiol (E2) and/or TAM. In the animal experiment in vivo, MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release E2 pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into four groups: 1) an E2 (0.72 mg/pellet) pellet [E2(+)]; 2) an E2 and a TAM (5 mg/pellet) pellet [E2(+)TAM]; 3) no treatment [E2(-)] and 4) a TAM pellet [E2(-)TAM]. Following each treatment for 4 weeks, all animals were sacrificed and tumors were removed. Specimens, cells (in vitro) or tumors (in vivo), were homogenized and assayed for FN by Western blots. In the in vitro experiment, FN expression in MCF-7 cells decreased by incubating with 10(-9) M E2 and increased with 10(-6) M TAM. The effect of TAM increasing FN expression was inhibited by incubation accompanied with 10(-9) M E2 or 1 microg/ml transforming growth factor-beta (TGF-beta) neutralizing antibody. In the in vivo animal experiment FN expression in the tumors of E2(+) mice was lower than that of E2(-) mice. However, TAM increased FN expression in the tumors regardless of E2 pellet. These results suggest that TAM increases FN expression of MCF-7 breast carcinoma cells and that these regulatory effects of TAM on FN expression are partly mediated by TAM-induced TGF-beta.

Significance of local recurrence as a prognostic factor in the treatment of breast cancer.

The aim of this study was to evaluate both the risk factors of local recurrence and the prognostic significance of local recurrence in relation to surgical treatment and/or radiation therapy of breast cancer. A total of 1574 primary breast cancer patients, undergoing surgical treatment and/or radiation therapy between 1980 and 2001, were included in this study. Radical mastectomy was performed in 1144 patients, subcutaneous mastectomy in 141 and breast-conserving therapy in 289. The clinical stage was significantly earlier in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. A positive surgical margin was observed in 9 (6.4%) out of 141 patients in the subcutaneous mastectomy group and 51 (176%) out of 289 in the breast-conserving therapy group. Local recurrence occurred more frequently in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. Independent prognostic factors in local recurrence were lymph node metastasis in the radical mastectomy group, and surgical margin in the subcutaneous mastectomy group and the breast-conserving therapy group. Independent prognostic factors in overall survival were local recurrence, lymph node metastasis and estrogen receptor status in the radical mastectomy group, and lymph node metastasis and estrogen receptor status in the breast-conserving therapy group. In conclusion, the surgical margin status is an important factor in the risk of local recurrence in patients who have undergone a subcutaneous mastectomy or breast-conserving therapy. The significance of local recurrence for overall survival may be different among these three treatments.

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report.

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 microg/L. The area under the curve of paclitaxel was 4398.6 microg x h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 micromol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.

Xanthogranulomatous cholangitis causing obstructive jaundice: a case report.

This article reports the case of a 34-year-old woman with xanthogranulomatous cholangitis who developed obstructive jaundice. Microscopically, the bile duct was surrounded and narrowed by a xanthogranulomatous lesion, but no xanthogranulomatous cholecystitis was seen. Although percutaneous cholangiograms done via the transhepatic biliary drainage showed smooth narrowing of the upper to middle bile duct, the cytology of bile was diagnosed as class V adenocarcinoma. Therefore, right extended hepatectomy and extrahepatic bile duct resection were performed. The differentiation of benign and malignant strictures at the hepatic hilum is often difficult. Xanthogranulomatous cholangitis is one possible diagnosis of a bile duct stricture. Precise review of all the preoperative information is required to make a correct diagnosis.

The role of mitogen-activated protein kinases and the participation of intestinal congestion in total hepatic ischemia-reperfusion injury.

BACKGROUND/AIMS: The mitogen-activated protein kinase (MAPK) pathways are comprised of key regulatory proteins that control the cellular responses to both proliferation and stress signals. This study was performed to examine the degree of liver damage and MAPK activation induced by ischemia of varying durations, and the association between intestinal congestion and liver dysfunction after hepatic ischemia-reperfusion injury. METHODOLOGY: Male Sprague-Dawley rats were divided into five groups: sham-operated controls (no hepatic ischemia); 15, 30, or 45 min of total hepatic ischemia; or 45 min of total hepatic ischemia with a portosystemic shunt. Serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin-1beta and tumor necrosis factor-alpha, as well as liver tissue blood flow were measured. Liver was also sampled for MAPK analysis and histopathological examination. RESULTS: Total hepatic ischemia for over 30 min, with intestinal congestion, caused severe liver damage and an inflammatory cytokine response. A portosystemic shunt attenuated ischemia-reperfusion injury and inhibited inflammatory cytokine expression. Extracellular signal-regulated kinase was markedly phosphorylated in all groups other than the sham-operated group. p38 MAPK and c-Jun N-terminal kinase were highly phosphorylated in all groups receiving 30 min or more of ischemia. CONCLUSIONS: Prolonged warm total hepatic ischemia-reperfusion injury is associated with small intestinal congestion; a portosystemic shunt reduces liver damage by inhibiting inflammatory cytokine expression. MAPKs are markedly phosphorylated after reperfusion.

Superior vena cava rupture caused during balloon dilation for treatment of SVC syndrome due to repetitive catheter ablation--a case report.

A 29-year-old woman with an implanted AAI mode permanent pacemaker, who had undergone catheter ablation for inappropriate sinus tachycardia 4 times, experienced complications of superior vena cava (SVC) syndrome. Severe stenosis of the SVC wall was observed in computed tomograms. During balloon dilation for the treatment of SVC syndrome, the SVC was ruptured, resulting in cardiac tamponade. An emergency operation was performed using percutaneous cardiopulmonary support (PCPS). A longitudinal tear 1 cm in length was identified at the junction of the right atrium and the SVC, requiring a patch plasty using an autologous pericardium 2.5 cm x 3 cm in size. SVC rupture is a complication to be completely avoided when we perform balloon dilation for the treatment of SVC syndrome. Therefore, the indication of balloon dilation for the treatment of SVC syndrome requires critical examination and attention.

Surgical treatment with deep hypothermia for thoracic aortic aneurysm in a patient with renal transplantation.

An increasing number of patients have undergone aortic reconstruction, exposing the transplanted kidney to ischemic injury. A 58-year-old male underwent renal transplantation previously. A thoracic aortic aneurysm (TAA) of the distal aortic arch was identified. His renal function was poor due to chronic rejection. The TAA was exposed by a left anterolateral thoracotomy through the 4th intercostal space, and cardiopulmonary bypass established with canulation of the left femoral artery and vein. Deep hypothermic circulatory arrest with retrograde cerebral perfusion was adopted at a rectal temperature of 20 degrees C, and distal arch replacement was successfully performed. Prednisolone was administered intravenously for perioperative immunosuppression. Poor renal function recovered to the preoperative level. No other complications occurred. Perioperative renal graft protection, immunosuppression and infection control are mandatory for surgical treatment in patients with TAA after renal transplantation.

[A recurrent endocrine cell cancer of the stomach showing almost complete remission after chemotherapy for 1 year].

We report a recurrent case of gastric endocrine cell cancer that showed a remarkable response to systemic chemotherapy. A 70-year-old male who underwent gastroscopy at our hospital showed a 0-IIa-like lesion, but no abnormal CT findings. He was diagnosed with gastric cancer, and underwent a proximal gastrectomy. The resected specimen showed endocrine cell cancer. The tumor was Grimelius-positive histologically and chromogranin A-and NSE-positive immunohistochemically. About 2 years after surgery, liver, lymph node, and bone metastases were detected. Systemic chemotherapy with TS-1 and CDDP was started, and the lesions progressed. Then, by approximately 1 year after CDDP and CPT-11 treatments, the recurrent lesions had diminished remarkably and were no longer seen on CT or FDG-PET.

Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer.

OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is considered a poor-prognostic factor, further information is lacking, especially in relation to other clinicopathologic prognostic factors. We assessed the relationship between visceral pleural invasion and other clinicopathologic characteristics and evaluated its significance as a prognostic factor. METHODS: We reviewed 1074 patients with surgically resected T1/2 non-small cell lung cancer for their clinicopathologic characteristics and prognoses. The patients were divided into 2 groups according to visceral pleural invasion status (visceral pleural invasion group and non-visceral pleural invasion group). Both groups were compared with regard to age, sex, histology, tumor size, tumor differentiation, lymph node involvement, lymphatic invasion, vascular invasion, scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level, and survival. Univariate and multivariate analyses were conducted. RESULTS: Visceral pleural invasion was identified in 288 (26.8%) of the resected specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non-visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in the visceral pleural invasion group. The difference between groups was highly significant ( P < .0001). Visceral pleural invasion was also significantly associated with a higher frequency of lymph node involvement. However, regardless of N status (N0 or N1/2), there was a significant difference in survival when the visceral pleura was invaded. Visceral pleural invasion was observed significantly more frequently in tumors with factors indicative of tumor aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion, vascular invasion, high scar grade, high nuclear atypia grade, high mitotic index, and high serum carcinoembryonic antigen level. By multivariate analysis, visceral pleural invasion proved to be a significant independent predictor of poor prognosis in non-small-cell lung cancer patients with or without lymph node involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor-prognostic factor, regardless of N status. Our analyses indicated that visceral pleural invasion is an independent indicator of non-small cell lung cancer invasiveness and aggressiveness.

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.

Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer.

The purpose of this study was to analyze whether inter-site variation types on estrogen receptor (ER) and HER2 expression may be a predictive factor for evaluating the effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER-2 status was evaluated according to the HercepTest. In ER-positive and HER2-positive tumors, the expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2. Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER-2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER2 status was inversely correlated (p<0.01) with ER status. In ER-positive tumors, an inverse correlation between ER and HER2 was also observed. The co-expressed type was found in 10 patients, and the differently expressed type was found in 18. There was no difference in tumor size and nodal involvement between the two types. There was no significant difference in disease-free survival between patients with the co-expressed type tumor and the differently expressed type tumor. In patients with the differently expressed type tumor, those who received antiestrogen therapy showed a significantly better disease-free survival rate than those who did not receive antiestrogen therapy. As for patients with the co-expressed type of tumor, no significant difference in disease-free survival was observed between patients with and without antiestrogen treatment. The present study suggests that the co-expressed type of tumour might be a resistant factor to antiestrogen therapy in ER-positive and HER2-positive breast cancer.

Local control by breast-conserving surgery with nipple resection.

Local control was compared between patients who had undergone breast-conserving therapy with and without nipple resection. We explored whether there was any difference in local control between the two treatment methods for patients with early breast cancer. A total of 333 women with breast cancer, who had undergone breast-conserving therapy between 1991 and 2002, were included in this study. Surgery consisted of a wide local excision of the primary tumor with a 2-cm free margin as the minimum distance. When the tumor was located under the nipple or close to the nipple, breast-conserving surgery with nipple resection was selected. A total of 320 patients received breast-conserving surgery without nipple resection and radiation therapy (BCT) and 13 patients breast-conserving surgery with nipple resection and radiation therapy (BCT-NR). There were no significant differences in age, tumor size, nodal status, clinical stage, ER status, histological type or surgical margin status between the two groups. The surgical margin was positive in 55 (17.2%) out of 320 patients in the BCT group and in one (7.7%) out of 13 patients in the BCT-NR group. There was no significant difference in the breast-free survival between the two groups. In conclusion, breast-conserving surgery with nipple resection and radiation therapy may be the treatment of choice for early breast cancer patients with the tumor located under the nipple or very close to the areola.

A combination phase I study of weekly paclitaxel and doxifluridine in advanced gastric cancer patients.

BACKGROUND: Preclinical studies have shown that paclitaxel and doxifluridine can act synergistically without overlapping toxicity for the treatment of advanced gastric cancer. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose-limiting toxicity and the recommended Phase II dose for this drug combination. PATIENTS AND METHODS: Patients with histologically confirmed gastric cancer were eligible for the study. The paclitaxel dose (days 1, 8, 15) was augmented with a fixed dose of for treatments (1-3). doxifluridine (533 mg/m2, 5 days/week) on a 28-day cycle. RESULTS: Eighteen patients were enrolled. The MTD was not reached until the highest dose level. One patient had Grade 3 myelosuppression. The responses of the 13 suitable patients included 1 complete response and 5 partial responses. CONCLUSION: Although the MTD level could not be definitively which is a established, upon consideration of the lengthy administration time and the effectiveness, the recommended Phase II dose of paclitaxel was concluded to be 80 mg/m2 in combination with doxifluridine at 533 mg/m2.

NO donor ameliorates ischemia-reperfusion injury of the rat liver with iNOS attenuation.

This study investigated the effect of a spontaneous nitric oxide (NO) donor, FK409 (FK), in a rat model of segmental hepatic ischemia. Rats were allocated to four experimental groups. Two of the groups underwent segmental hepatic ischemia of 60 min duration and received FK (0.4 mg/kg, iv) or vehicle alone before inducing ischemia and again 5 min before reperfusion. Sham-FK and sham groups were treated identically, but did not have vascular occlusion. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) were measured, and the livers were examined for histological evidence of injury, polymorphonuclear neutrophil (PMN) infiltration, and immunohistochemical expression of inducible NO synthase (iNOS) before and 6 h after reperfusion. AST, ALT, and LDH levels were significantly (p < .05) reduced 6 h after reperfusion in the FK-treated group compared with the vehicle-treated control group. FK treatment also reduced the degree of hepatic damage apparent on histopathology and reduced PMN infiltration and iNOS expression. Thus, FK treatment is protective against hepatic ischemia reperfusion injury and attenuates neutrophil infiltration and iNOS expression.