Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions.

PURPOSE: The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. METHODS: We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. RESULTS: The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. CONCLUSION: Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.

Malfunction of the da Vinci robotic system in urology.

OBJECTIVES: To analyze the incidence of malfunction of the da Vinci robotic system in a single center and to provide potential solutions. METHODS: A total of 400 patients underwent da Vinci robotic urological surgery at Taichung Veterans General Hospital in Taichung, Taiwan, from December 2005 to April 2011. Episodes of malfunction of the robotic system were analyzed by period of operation, type of procedure, type of malfunction and management of the event. RESULTS: Overall, 14 cases of malfunction occurred (3.5% of the entire series). Among them, five (1.25%) occurred before the surgery and nine (2.25%) intraoperatively. Operative procedures included radical prostatectomy, bilateral pelvic lymph node dissection, dismembered pyeloplasty, partial nephrectomy, nephroureterectomy, and radical and partial cystectomies. Areas of malfunctions included the robotic arm system and joint (11/14), optical system (1/14), power system and connector (1/14), endoscopic instrument (1/14), and software (1/14). In 10 cases, the failure was recoverable, whereas in four cases there was a critical failure, requiring a conversion to standard laparoscopy in three of them, and the rescheduling of the surgery in one case. CONCLUSIONS: The da Vinci robotic system is extremely reliable for use in urology. Malfunction is rare and the risk of critical failure is very low. Managing mechanical failure before or during the surgery is the key to maintaining the safety of patients undergoing robotic surgical procedures.

Genetic polymorphism of the plasminogen activator inhibitor-1 is associated with an increased risk of endometrial cancer.

BACKGROUND AND OBJECTIVES: To investigate the association of uPA system genes, including uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 gene polymorphisms, with risk of endometrial cancer. METHODS: In the present case control study, we enrolled a total of 134 patients with endometrial cancer confirmed by histopathology and 302 unrelated healthy individuals. Genetic polymorphisms of uPA system genes, including uPA rs4065 C/T SNP, uPAR rs344781 T/C SNP, and PAI-1 rs1799889 4G/5G SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. RESULTS: Frequency of PAI-1 rs1799889 4G/4G genotype and 4G allele differed significantly between patients with endometrial cancer (36.6% and 61.6%, respectively) and healthy individuals (25.5% and 52.2%, respectively). Individuals with PAI-1 rs1799889 4G/4G genotype were at higher risk of endometrial cancer (OR = 2.26; 95% CI: 1.20-4.27). Stratification analysis showed individuals with PAI-1 rs1799889 4G/4G genotype were at elevated risk for endometrioid type (OR = 2.49; 95% CI 1.27-4.88), low stage (stages I-II) endometrial cancer (OR = 2.34; 95% CI 1.21-4.52). However, no significant differences in uPA C/T SNP, uPAR T/C SNP genotypes were observed between endometrial carcinoma cases and controls. CONCLUSIONS: Individuals with PAI-1 rs1799889 4G/4G genotype were at significantly higher risk of endometrial cancer in this study.

Partial nephrectomy in the treatment of localized renal cell carcinoma: experience of Taichung Veterans General Hospital.

BACKGROUND: Partial nephrectomy has been considered an effective and efficient method in the treatment of localized renal cell carcinoma. Herein, we retrospectively review our experience with partial nephrectomy in the treatment of localized renal cell carcinoma and compared it with patients who received radical nephrectomy. METHODS: From 1982 to 2005, 35 patients who received partial nephrectomy for localized renal cell carcinoma were enrolled in this study. Ten patients were female (28.6%). The median age was 70 years (range, 42-82 years). Sixteen (45.7%) patients had pathologic T1a tumors; 17 (48.6%) patients had pathologic T1b tumors and 2 (5.7%) patients had pathologicT2 tumor (7cm). In the meantime, 128 patients who had T1N0M0 renal cell carcinoma and who received radical nephrectomy were assigned to a control group. Thirty-nine patients (30.5%) were female in this group. The median age was 62 years (range, 30-83 years). The tumor characteristics, location, surgical techniques and patient survival were subsequently compared. RESULTS: The median tumor size in the partial nephrectomy group was 3.9cm (range, 1.5-7.0cm), and it was 4.5cm (range, 1-6.5cm) in radical nephrectomy group. The tumor size was smaller in the partial nephrectomy group (p = 0.003). Themedian follow-up period was 4.38 years (range, 0.05-17.99 years) in the partial nephrectomy group and 5.66 years (range, 0.01-22.25 years) in the radical nephrectomy group. There was no local recurrence or distant metastasis in the partial nephrectomy group. The 5-year overall survival was 85.0% compared with 91.4% in the radical nephrectomy group (p = 0.126). The 5-year disease specific survival in the partial nephrectomy group was 100%. The postoperative serum creatinine level increased to >2.0mg/dL in 5 (14.3%) patients in the partial nephrectomy group, but no patient needed hemodialysis during follow-up. CONCLUSION: From our review, partial nephrectomy is safe and provides excellent disease control in the treatment of localized renal cell carcinoma in selected patients. Renal function preservation was observed in the partial nephrectomy group, while the operated kidney showed functioning in the follow-up nuclear medicine survey.

Nortriptyline induces mitochondria and death receptor-mediated apoptosis in bladder cancer cells and inhibits bladder tumor growth in vivo.

Nortriptyline (NTP), an antidepressant, has antitumor effects on some human cancer cells, but its effect on human bladder cancer cells is not known. In this study, we used a cell viability assay to demonstrate that NTP is cytotoxic to human TCCSUP and mouse MBT-2 bladder cancer cells in a concentration and time-dependent manner. We also performed cell cycle analysis, annexin V and mitochondrial membrane potential assays, and Western blot analysis to show that NTP inhibits cell growth in these cells by inducing both mitochondria-mediated and death receptor-mediated apoptosis. Specifically, NTP increases the expression of Fas, FasL, FADD, Bax, Bak, and cleaved forms of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. In addition, NTP decreases the expression of Bcl-2, Bcl-xL, BH3 interacting domain death agonist, X-linked inhibitor of apoptosis protein, and survivin. Furthermore, NTP-induced apoptosis is associated with reactive oxygen species (ROS) production, which can be reduced by antioxidants, such as N-acetyl-L-cysteine. Finally, we showed that NTP suppresses tumor growth in mice inoculated with MBT-2 cells. Collectively, our results suggest that NTP induces both intrinsic and extrinsic apoptosis in human and mouse bladder cancer cells and that it may be a clinically useful chemotherapeutic agent for bladder cancer in humans.

The symptoms of renal cell carcinoma related to patients' survival.

BACKGROUND: The aim of this study was to compare outcomes in patients presenting with incidental renal cell carcinoma (RCC), symptomatic RCC and paraneoplastic syndromes in RCC. METHODS: From October 1982 to June 2001, 312 patients with RCC were retrospectively enrolled. The patients were classified as: 1) incidental group: the patients without symptoms whose tumor was discovered incidentally; 2) symptomatic group: the patients presenting symptoms related to renal tumor; 3) paraneoplastic syndrome group: patients whose tumors were associated with paraneoplastic syndromes. Log rank testing was used to analyze statistical differences in the survival period among the three groups. RESULTS: The distribution of each group was 25.6% (n = 80) in group 1, 55.8% (n = 174) in group 2 and 18.6% (n = 58) in group 3. The mean tumor size was 5.0 cm in group 1, 7.5 cm in group 2 and 8.3 cm in group 3 (p < 0.0001). The incidence of earlier stage (stages I and II) was 80% in group 1, 40.2% in group 2 and 15.5% in group 3 (p < 0.0001). The 10-year survival rate for group 1 patients was 68.6%, for group 2 patients was 45.6% and for group 3 patients was 12.3% (p < 0.0001). CONCLUSIONS: The incidental RCCs were smaller in size and at a lower tumor stage than symptomatic tumors. The paraneoplastic syndromes in patients with RCCs had a grave prognosis. The symptoms of a patient with RCC can be used as a prognostic factor related to survival.

Application in robotic urologic surgery.

BACKGROUND: The da Vinci robot system has become the mainstay of minimally invasive surgery and has been used in numerous complex reconstructive procedures. Due to the success of this innovative technology, we attempted to expand our practical model and application of the da Vinci robot system into other urologic surgeries, beginning with robotic-assisted laparoscopic radical prostatectomy (RALRP). METHODS: We retrospectively reviewed a total of 683 patients who underwent robotic-assisted urologic surgery between December 2005 and December 2012. We divided this 8-year course of device use into three periods, and analyzed the surgical capability of operations in 1 day over different periods through a retrospective analysis. RESULTS: In the first period (2005-2008), 159 cases of robotic-assisted urologic surgeries were performed. A total of 195 cases were performed in the second group (2009-2010), and 329 cases in the third (2011-2012). Starting with radical prostatectomy in December 2005, we performed various types of procedures such as partial nephrectomy, pyeloplasty, nephroureterectomy with cystoprostatectomy, nephroureterectomy with bladder cuff, radical cystoprostatectomy/cystectomy with ileal conduit reconstruction, partial cystectomy, adrenalectomy, nephropexy, simple prostatectomy, ureteral reconstruction, and pyelolithotomy/ureterolithotomy. The mean operation times of prostatectomy, partial nephrectomy, nephroureterectomy with radical cystectomy/cystectoprostatectomy, and nephroureterectomy were 154, 140, 295, and 129 minutes, respectively. CONCLUSION: Based on our experience, a robotic system can be applied to many different types of urologic surgeries both safely and efficiently.

Association of estrogen receptor α gene PvuII and XbaI polymorphisms with non-small cell lung cancer.

Single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER)-α have been found to be associated with various diseases at significantly different frequencies. However, whether any relationship exists between ER-α polymorphisms and lung cancer remains to be determined. In this study, 84 non-smoking, female, non-small cell lung cancer patients with various stages of disease and 234 cancer-free reference controls were enrolled to examine the association of ER-α polymorphisms in lung cancer. Two restriction SNP sites, PvuII and XbaI, in the first intron of the ER-α gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the PvuII-XbaI haplotypes and genotypes in a Taiwanese population were revealed for the first time. Although the genotypic frequencies of two polymorphic sites of ER- α were in linkage disequilibrium for the lung cancer group (χ(2)=50.013, d.f.=4) and reference controls (χ(2)=60.797, d.f.=4); and 7 and 8 combined genotypes were present, respectively, the distribution and the major genotypes are different in the two groups (p<0.0001). The p-values for PvuII and XbaI genotypes were significantly different between the lung cancer and reference controls. The PP genotype presence was found to be significantly lower in the lung cancer group (P=0.005), whereas presence of the xx genotype was significantly higher (P=0.042). These findings suggested that the PP genotype had a lower risk of lung cancer; whereas the xx genotype had a higher risk. In comparison with other studies conducted in various populations, it is of note that the pX haplotype frequency of this study was higher than that of other studies, whereas the px haplotype was lower. Moreover, the Xx genotypic frequency of XbaI polymorphisms in the ER-α gene of the reference control group was found to be extremely high, whereas the xx genotypic frequency was extremely low. In conclusion, PvuII-XbaI polymorphisms of the ER-α gene were found to be associated with the risk, but not cancer severity, of non-small cell lung cancer in a Taiwanese population.

Trends in treatment for localized prostate cancer after emergence of robotic-assisted laparoscopic radical prostatectomy in Taiwan.

BACKGROUND: Radical retropubic prostatectomy remains the gold standard treatment for localized prostate cancer. However, new minimally invasive techniques have emerged, providing a less invasive approach. Robotic-assisted laparoscopic radical prostatectomy is the ideal technique, providing good oncologic and functional outcomes. We analyzed the impact of robotic surgical systems on practice patterns among urologists to explain changes in the value of radical retropubic prostatectomy, laparoscopic radical prostatectomy and robotic-assisted laparoscopic radical prostatectomy in a single institution in Taiwan. METHODS: We retrospectively reviewed the records of patients who received prostatectomy by one of the above procedures between January 2004 and November 2009. Decisions to perform these procedures were made by patient preference. Patients who received prostate biopsies at other hospitals were transferred to our hospital specifically for robotic-assisted prostatectomy. RESULTS: A total of 434 radical prostatectomies were performed, of which 141 (32.49%) were radical retropubic prostatectomies, 59 (13.59%) were laparoscopic radical prostatectomies and 234 (53.92%) were robotic-assisted laparoscopic prostatectomies. The overall number of prostatectomies has increased over time because of an increase in robotic-assisted procedures. No decreases were seen in the number of radical retropubic prostatectomies during the evaluation period. Changes in the ratio of robotic-assisted prostatectomies compared to radical retropubic and laparoscopic radical prostatectomies demonstrated a trend toward robotic-assisted procedures. The percentage of cases transferred from other hospitals also increased over time from 28.57% to 68.60%. CONCLUSION: Our experience emphasizes the potential of robotic-assisted prostatectomy to become the mainstream treatment for localized prostate cancer in Taiwan.

Metallic stent in the treatment of ureteral obstruction: experience of single institute.

BACKGROUND: The Resonance(®) metallic stent has been reported to be sufficient for the management of malignant extrinsic ureteral obstructions within a 12-month time period. To determine the effectiveness in each specific patient group, we report our experience using the Resonance(®) stent in the treatment of ureteral obstructions. METHODS: We retrospectively reviewed 20 patients (23 stents) who successfully received the Resonance(®) metallic stents and divided them into a patent group (n = 19) and an obstructive group (n = 4) according to the treatment results. Twenty-one stents were inserted via cystoscopy or ureteroscopy in a retrograde fashion. The remaining two were inserted via percutaneous nephrostomy in an antegrade manner. Follow-up serum creatinine measurements and sonography were performed. The overall ureteral patency rate and the risk of stent failure were evaluated. RESULTS: The overall ureteral patency rate was 82.6% (19/23). Patients with previous radiotherapy had a 50% (4/8) patency rate which was significantly lower than non-radiotherapy patients (100%, 15/15, p = 0.028). Malignant obstructions in those other than radiotherapy patients had a 100% patency rate (5/5). Benign obstructions in those other than radiotherapy patients had a 100% patency rate (10/10). In the radiotherapy patients, the mode of therapy did not dominate the stent outcome. CONCLUSION: Patients with ureteral obstructions can be treated sufficiently with the Resonance(®) metallic stent. Patients who had gynecological malignancies and received radiotherapy had a higher failure rate after Resonance(®) metallic stent insertion.

Osteoclast-like giant cell carcinoma of the urinary bladder.

Extraskeletal osteoclast-like giant cell (OGC) tumors are uncommon and have mainly been found in the breast and pancreas. OGC neoplasms of the urinary tract are extremely rare, and their histogenesis and biologic behavior remain controversial. Gross hematuria is the most common presenting symptom, as in transitional cell carcinoma. The prognosis is poor in patients with extraskeletal OGC tumors. Here, we present the case of a 62-year-old man who received transurethral bladder tumor resection due to painless gross hematuria. Pathology showed OGC carcinoma. Abdominal computed tomography showed tumor invasion over the right lateral wall of the bladder and distal third of the ureter. The patient received radical cystectomy and partial distal ureterectomy with transureteroureterostomy. No local tumor recurrence or distant metastasis was found at the 5-month follow-up.

Initial clinical experience with surgical technique of robot-assisted transperitoneal laparoscopic partial nephrectomy.

BACKGROUND: The incidental finding of small renal masses has increased due to widespread use of computed tomography as a diagnostic procedure. Some patients with either exophytic renal masses less than 4 cm and suboptimal renal function, a solitary kidney and bilateral renal tumors, or genetic predisposition to renal tumors are considered candidates for laparoscopic partial nephrectomy (LPN). A technical difficulty of LPN is performing laparoscopic intracorporeal suturing under the pressure of warm ischemia time. Because robotic systems have been shown to provide easier intracorporeal suturing, we hypothesized that robotic-assisted LPN might improve efficacy. METHODS: Eight patients with a mean age of 41 years and mean tumor size of 2.3 cm underwent robot-assisted LPN between September 2006 and December 2008. Tumor excision and intracorporeal suturing under warm ischemia by renal artery clamp were performed entirely using a robotic system. All perioperative data and pathologic results were reviewed retrospectively. RESULTS: The mean operation time was 160 minutes, and the mean estimated blood loss was 165 mL. The mean warm ischemia time was 33 minutes, and mean postoperative hospital stay was 4.3 days. Average preoperative hemoglobin was 13.0 mg/dL and postoperative hemoglobin was 11.8 mg/dL. Average preoperative creatinine was 1.1 ng/mL and postoperative creatinine was 1.28 ng/mL. There was 1 conversion to laparoscopic nephrectomy due to a positive margin on a frozen section after discussion with family about better oncologic control. The resected lesions included renal cell carcinoma in 5 patients, angiomyolipoma in 2, and a renin-secreting renal tumor in 1 patient. CONCLUSION: Robot-assisted LPN is feasible and may be a viable alternative to open or LPN in selected patients with small exophytic renal tumors. Compared with standard LPN, the robotic assisted LPN approach with precise renal reconstruction under a safe warm ischemia time is feasible and can be easily adopted by those with experience in robot-assisted surgery.

Transitional cell carcinoma in renal transplant recipients.

Renal transplantation (RTx) recipients have a high incidence of cancer, including transitional cell carcinoma (TCC). Posttransplantation urologic malignancies still present a challenge for transplant surgeons. Using the Dialysis and Transplant Registry of Taichung Veterans General Hospital, a total of 55 cancers were diagnosed in 52 RTx recipients between May 1983 and September 2001. Of these, 24 RTx recipients developing TCC were identified and presented the distinctly high percentage (43.6%) of TCC that were malignancies after RTx in Taiwan. The mean time between transplantation and initial diagnosis was 46 months in our series. Painless hematuria with pyuria is the most common mode of presentation. Transitional cell carcinoma of RTx recipients had multiple foci. Moreover, synchronous TCC in bilateral upper urinary tracts were confirmed in 9 (41%) recipients. The pathologic status of disease is invasive at diagnosis (pTa: 2, pT1: 7, pT2: 4, pT3: 6, pT4: 2, graft metastasis: 1 and distant metastasis: 2). Disseminated metastasis occurred in 6 recipients, all of whom died of their disease within 16 months. Five recipients received adjuvant chemotherapy and retained stable renal function. We conclude that RTx recipients have a markedly increased incidence of TCC in Taiwan, and that prophylactic bilateral nephroureterectomy of native kidneys with bladder cuff excision can be performed simultaneously in RTx recipients with TCC.

Efficacy and safety of on-demand oral tadalafil in the treatment of men with erectile dysfunction in Taiwan: a randomized, double-blind, parallel, placebo-controlled clinical study.

INTRODUCTION: Tadalafil is a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction (ED). Past clinical trials have assessed its efficacy and safety in western populations. Tadalafil has not been investigated in a large clinical trial with a South-east Asian population. AIM: To assess the efficacy and safety of on-demand tadalafil for the treatment of ED in a 12-week, double-blind, placebo-controlled study in Taiwan. METHODS: Men with mild to severe ED of various etiologies were randomized to receive placebo, tadalafil 10 mg, or tadalafil 20 mg, taken as needed (maximum once daily). Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). RESULTS: Tadalafil significantly improved erectile function compared with placebo (P < 0.005, all measures). At endpoint, the patients receiving tadalafil reported a greater mean per-patient percentage of successful intercourse attempts (SEP question 3: 70.0%, 10 mg; 78.0%, 20 mg) than placebo-treated patients (42.8%) and a greater proportion of improved erections (GAQ: 92.3% and 84.6% vs. 54.5%). Most treatment-emergent adverse events were mild or moderate. The most common adverse events were back pain, dyspepsia, and myalgia. CONCLUSIONS: Tadalafil was an effective, well-tolerated therapy for men in Taiwan with ED of broad-spectrum severity and etiology.