Gemcitabine and cisplatin therapy in advanced or metastatic urothelial cancer: comparison of side effect with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)

OBJECTIVE: Cisplatin-based combination chemotherapy has been considered as standard therapy for advanced or metastatic urothelial carcinoma. A recent study has, however, revealed that gemcitabine may have the potential to act synergistically with cisplatin. Therefore, the side effects of gemcitabine plus cisplatin (GC) therapy were compared with those of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) therapy in patients with advanced or metastatic urothelial carcinoma. PATIENTS AND METHODS: Twenty-two patients received GC therapy. Gemcitabine (1000 mg/m2) was administered on days 1, 8 and 15 of each 28-day cycle. Cisplatin (70 mg/m2) was administered on day 2 of each cycle. As a control group, 24 patients received MVAC therapy (methotrexate at 30 mg/m2 on days 1, 15, 22, vinblastine at 3 mg/m2 on days 2, 15, 22, doxorubicin at 30 mg/m2 on day 2, and cisplatin at 70 mg/m2 on day 2 of each 28-day cycle. RESULTS: In the group of patients which received GC therapy, the overall response rates based on independent radiologic reviews of the 20 patients with measurable disease were 55%, with 20% CR and 35% PR. Fewer GC patients as compared with MVAC patients had grade 3/4 anorexia (4.5% vs. 75%, respectively), stomatitis (9.0% vs. 66.7%, respectively), and alopecia (27.3% vs. 100%, respectively). On the other hand, there were no significant differences in the incidence or pattern of hematologic toxicities between the group receiving GC therapy and that receiving MVAC therapy. Fatal neutropenic sepsis occurred in one patient receiving MVAC therapy. CONCLUSION: GC therapy is effective for the treatment of advanced or metastatic urothelial carcinoma, with an acceptable clinical safety profile. This study also indicates that GC therapy may be better tolerated and safer than MVAC therapy.     

Effects of landiolol on hemodynamic response and seizure duration during electroconvulsive therapy

Purpose This study was done to evaluate the effect of landiolol, an ultra-short-acting beta-blocker, on the hemodynamic response and the duration of seizure activity during electroconvulsive therapy (ECT). Methods We designed a prospective, randomized, double-blinded, placebo-controlled, crossover study. Fourteen psychiatric patients participated. Landiolol (0.1 mg·kg⁻¹ or 0.2 mg·kg⁻¹) or saline (placebo) was administered IV 1 min before the induction of anesthesia. Unconsciousness was induced with propofol 1.0 mg·kg⁻¹ IV, and muscle paralysis was produced with succinylcholine 0.6 mg·kg⁻¹ IV. Subsequently, electrical stimulus was administered to elicit a seizure, and the duration of the motor seizure activity was noted. Results The heart rate (HR) and rate-pressure product (RPP) before ECT were significantly decreased in the 0.2 mg·kg⁻¹ landiolol group compared with these parameters in the placebo and 0.1 mg·kg⁻¹ landiolol groups. Both the 0.1 mg·kg⁻¹ and 0.2 mg·kg⁻¹ doses significantly attenuated the degree of tachycardia and RPP after ECT in comparison with the placebo group. Pretreatment with 0.2 mg·kg⁻¹ landiolol resulted in a significantly shorter duration of motor seizure than that in the placebo group (21 ± 13 s vs 27 ± 12 s). Conclusion As the landiolol dose of 0.2 mg·kg⁻¹ caused shorter seizure duration, and because the hemodynamic effects after ECT of the 0.1 mg·kg⁻¹ and 0.2 mg·kg⁻¹ doses were similar, it was concluded that a 0.1 mg·kg⁻¹ landiolol bolus was the appropriate dose pretreatment before ECT.     

Comparative analysis of interindividual variations in the seminal plasma proteome of fertile men with identification of potential markers for azoospermia in infertile patients

Seminal plasma is a potential source of biomarkers for many disorders of the male reproductive system. The identification and characterization of proteins in the seminal plasma by using two-dimensional (2-D) difference gel electrophoresis (DIGE) serve as a basis for estimating male infertility. However, individual variation remains an impediment to identifying disease-associated proteins. Therefore, it is necessary to examine the interindividual variations in the seminal plasma proteome of fertile men. The present study analyzed seminal plasma samples from 10 fertile men. The results from silver-stained 2-D DIGE were averaged to reduce gel to gel variations. Up to 501 spots (polypeptides) were detected on the averaged gels for the fertile men. The coefficient of variation (CV) of standardized abundance was calculated for 63 spots that were common to all 10 samples; the CV values ranged from 24.5% to 129.9% with a median value of 63.1%. These results demonstrate that the variability in protein expression among different fertile men is relatively high in seminal plasma compared with that in other human tissue samples. The 63 matched spots were compared with those from 10 patients with azoospermia. There was no common spot that was lost in all of the 10 patients, and 16 of these spots (25%) were present in each of the patients. We identified 4 and 1 candidate markers for nonobstructive and obstructive azoospermia, respectively. These results validate our method of identifying differences in the proteomic profiles of seminal plasma samples and provide an important basis for protein expression profiling and comparative proteomics of infertility.     

Combined vascular resection in operative resection for hilar cholangiocarcinoma: does it work or not?

BACKGROUND: It is still not clear how combined vascular resection affects the outcome of patients with hilar cholangiocarcinoma. Our aim was to evaluate implications of combined vascular resection in patients with hilar cholangiocarcinoma by analyzing the outcomes of all patients who underwent operative resection. METHODS: A total of 161 of 228 consecutive patients with hilar cholangiocarcinoma underwent bile duct resection with various types of hepatectomy (88%) and pancreaticoduodenectomy (4%). Combined vascular resection was carried out in 43 patients. Thirty-four patients had portal vein resection alone, 7 patients had both portal vein and hepatic artery resection, and 2 patients had right hepatic artery resection only. The outcomes were compared between the 3 groups: the portal vein resection alone (34), hepatic artery resection (9), and non-vascular resection (118). RESULTS: Histologically-positive tumor invasion to the portal vein beyond the adventitia was present in 80% of 44 patients undergoing combined portal vein resection. Operative mortality occurred in 11 (7%) patients. The survival rates of the non-vascular resection group were better than that of the portal vein resection alone and the hepatic artery resection groups: 1, 3, and 5 years after curative resection, 72%, 52%, and 41% versus 47%, 31%, and 25% (P < .05), and 17%, 0%, and 0% (P < .0001), respectively. Multivariate analysis showed 4 independent prognostic factors of adverse effect on survival after operation; operative curability, lymph node metastases, portal vein resection, and hepatic artery resection. CONCLUSIONS: Although both portal vein and hepatic artery resection are independent poor prognostic factors after curative operative resection of locally advanced hilar cholangiocarcinoma, portal vein resection is acceptable from an operative risk perspective and might improve the prognosis in the selected patients, however, combined hepatic artery resection can not be justified.     

Improvements to staged canal wall up tympanoplasty for middle ear cholesteatoma

OBJECTIVE: To describe our improvements to staged canal wall up tympanoplasty with mastoidectomy (SCUT) for middle ear cholesteatoma, and to show more successful outcomes of the surgery compared with our data previously reported. STUDY DESIGN: Retrospective study in a tertiary referral hospital. SETTING: 78 ears of 76 patients with extensive cholesteatoma were operated on using the improved SCUT between July 1998 and December 2006. Improved SCUT included new techniques such as scutum plasty and mastoid cortex plasty performed in a staged manner. RESULTS: Only 2 ears showed retraction pocket formation (7.7%) without recurrence in 26 ears followed for more than 5 years. In 48 followed for more than 3 years, frequency of postoperative retraction pocket formation (5/48; 10.4%) was significantly lower compared to our previous results (41/134; 30.6%, P < 0.01). CONCLUSION: Our improvements to SCUT contributed to the decreasing of frequency of postoperative retraction pocket that may lead to cholesteatoma recurrence, although a longer follow-up study is required.     

Long-term effect of simvastatin on the improvement of impaired myocardial flow reserve in patients with familial hypercholesterolemia without gender variance

BACKGROUND: Impaired myocardial flow reserve (MFR) in patients with familial hypercholesterolemia (FH) without evidence of ischemia has been reported. However, it has not been clarified whether diminished MFR in such male or female patients with FH can be reversed by simvastatin. METHODS AND RESULTS: Sixteen patients with FH and 16 age-matched control subjects were studied. All patients were proved to have no evidence of exercise stress-induced myocardial ischemia. Baseline myocardial blood flow (MBF) and MBF during dipyridamole administration (MBF [DP]) were measured with positron emission tomography and nitrogen 13 ammonia; MFR was then calculated before and 9 to 15 months after therapy with simvastatin (5-10 mg/day). Total cholesterol level was significantly higher in patients with FH (277 +/- 49.0) than in control subjects (190 +/- 14.9) but was normalized after lipid-lowering therapy (205 +/- 40.3). Baseline MBF was comparable among FH patients before (77.6 +/- 11.6 mL/min/100 g) and after therapy (74.5 +/- 9.62 mL/min/100 g) and control subjects (78.5 +/- 29.9 mL/min/100 g). However, MBF (DP) in FH patients before therapy (178 +/- 50.9 mL/min/100 g) was significantly lower than that in control subjects (282 +/- 148 mL/min/100 g) and was significantly improved after therapy (228 +/- 91.6 mL/min/100 g, P <.05). In fact, there was no statistically significant difference in the MBF (DP) value in FH patients after therapy compared with that in control subjects (P =.09). MFR significantly improved after therapy in patients with FH (3.33 +/- 1.19 vs 2.27 +/- 0.625, P <.01) and was then statistically comparable to that in control subjects (3.54 +/- 1.11). Improvement of MFR was observed whether MBF (DP) before therapy was greater than or less than 200 mL/min/100 g. MFR was improved in both male and female patients with FH. There was a significant relationship between percent change in plasma total cholesterol concentration and percent change in MFR before and after lipid-lowering therapy (r = -0.57, P <.05). CONCLUSIONS: Diminished MFR in patients with FH without evidence of ischemia can be reversed by moderate- to long-term simvastatin therapy without gender variance.     

Evaluation of Preoperative Abdominal Adipose Tissue–, Inflammation-, Muscle Mass–, and Nutritional Status–based Prognostic Markers to Assess Renal Dysfunction in Living Kidney Donors

BackgroundLiving kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment.MethodsOur retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status–based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified.ResultsThe LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m², respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue–, inflammation-, nutritional status–, and muscle mass–based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN.ConclusionsOur findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.     

Clinical Significance of Postoperative Nutritional Status as a Prognostic Factor in Kidney Transplant Recipients

BackgroundDespite advancements in the management of kidney transplantation (KT), kidney transplant recipients (KTRs) have a higher risk of mortality than the age-matched general population. Improvement of long-term graft and patient survival is a significant issue. Therefore we investigated the effects of postoperative nutritional status on graft and patient survival and explored the predictive factors involved in nutritional status.MethodsOur retrospective study included 118 KTRs who underwent KT at our hospital. Clinical and laboratory data were obtained from medical charts. The prognostic nutritional index (PNI) was used to assess nutritional status. Changes in nutritional status after KT were monitored and the effect of nutritional status on graft and patient survival was investigated. The variables involved in nutritional status were also explored.ResultsThe KTRs in this cohort comprised 66 men and 52 women with a median age of 47 years at KT. There were 16, 32, and 22 cases of cadaveric, preemptive, and ABO-incompatible KTs, respectively. Postoperative PNI gradually improved and was stable from 6 months after KT. Although graft survival was regulated by ABO-compatibility, independent predictors for patient survival were history of dialysis, PNI, and serum-corrected calcium levels. Preemptive KT and inflammatory status contributed to PNI.ConclusionsNutritional status of KTRs improved over time after KT and could contribute to patient survival. Optimal nutritional educational programs and interventions can lead to better outcomes in KTRs. Further studies are needed to validate our results and develop appropriate nutritional educational programs, interventions, and exercise programs.     

Current topics in surgery for isolated total anomalous pulmonary venous connection

Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20 %. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10 %, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.